PROTEIN KINASE C MODULATORS WITH ANTI-INFLAMMATORY AND ANTIVIRAL ACTIVITY

Abstract: Compounds having anti-inflammatory and other activities are disclosed. The compounds are derived from diterpenes, aromatic heterocyclic compounds of the indole, indene, benzofuran and benzothiophene class and from polyacetates, diaminobenzyl alcohols, diacylglycerols and bryostatins.

Description: PROTEIN KINASE C MODULATORS WITH ANTI-INFLAMMATORY AND ANTIVIRAL ACTIVITY Background Protein kinase C is an enzyme found in nearly all animal tissues and animal cells that have been examined. Its identity is generally established by its ability to phosphorylate proteins when adenosine triphosphate and phospholipid cofactors are present, with greatly reduced activity when these cofactors are absent. Additionally, some forms of protein kinase C require the presence of calcium ions for maximal activity. Protein kinase C activity is also substantially stimulated by certain 1,2-sn- diacylglycerols that bind specifically and stoichiometrically to a recognition site on the enzyme. This site is called the diacylglycerol binding site, and it is located on the amino-terminal portion of protein kinase C, the so-called "regulatory domain". The carboxy-terminal portion of protein kinase C carries the site at which protein phosphorylation is effected, and this portion thus called the "kinase domain". Stimulation of protein kinase C by diacylglycerols has been shown to be an important physiological event that mediates the actions of a wide variety of hormones, neurotransmitters. and other biological control factors such as histamine. vasopressin, alpha-adrenergic agonists, dopamine agonists, muscarinic cholinergic agonists, platelet activating factor, etc. [see Y. Nishizuka. Nature 08 693-698 (1984) and Science 225 1365-1370 (1984) for reviews]. The biological role of protein kinase C is also of great interest because of the discovery that certain very powerful tumor promoting substances activate this enzyme by binding specifically and with very high affinity to the diacylglycerol binding site on the enzyme. In addition to diacylglycerols, there are at present five other known classes of compounds that bind to this site, including diterpenes such as the phorbol esters, indole alkaloids (indolactams) such as the teleocidins, lyngbyatoxin, and indolactam V, polyacetates such as the aplysiatoxins and oscillatoxins, certain derivatives of diaminobenzyl alcohol, and the macrocyclic lactones of the bryostatin class. The phorbol esters have long been known as powerful tumor promoters, the teleocidins and aplysiatoxins are now known to have this activity, and it appears likelv that additional classes of compounds will be found to have the toxic and tumor SUBSTITUTE SHEET promoting activities associated with the capability to bind to the diacylglycerol site of protein kinase C and thus activate the enzyme. Other toxicities of these agents when administered to animals include lung injury and profound changes in blood elements, such as leukopenia and neuropenia. In addition to potent tumor promoting activity, these six classes of compounds, collectively referred to as the "phorboids", display a vast range of biological activities, as would be expected from the widespread distribution of their target enzyme. Some of these activities, like tumor promotion, indicate the involvement of protein kinase C in important normal or pathological processes in animals. Thus, the phorboids are potent skin inflammatory agents, cause smooth muscle contraction in several tissues, alter immune system function and can be used to cause a variety of other normal or pathological responses. Related disease states such as the development of cancer, the onset and/or maintenance of inflammatory disease, the role of vasoconstriction in hypertension, the role of bronchoconstriction in asthma, the role of cholinergic, adrenergic, and dopaminergic synapses in diseases of the central/peripheral nervous systems, may be mediated in vivo by the stimulation of protein kinase C or other diacylglycerol binding site-bearing entities by diacylglycerols, the latter being generated in the cell by pathological agents or conditions. In analyzing the activity of a pharmaceutical or other bioactive compound, it is useful to consider two properties: the efficacy, defined as the capability to elicit a full or partial biological result, such as complete displacement of a ligand from its receptor site or the complete inhibition of inflammation or edema caused by a standard stimulus; and the potency, defined as that amount or concentration of drug that causes 50% of the full response (often abbreviated as the ED 0). It is frequently the case within a given class of pharmaceutical agents that individual members of the class all have equal efficacy, i.e. they each can generate a full biological effect, but they show differing potencies. Thus, the structural modifications within such a class affect only the amount necessary to achieve a given result, and the modified compounds otherwise have generally the same central biological characteristic. There may also be differences between members of such a class as regards properties other than the central biological characteristic; for example, members of the class might differ in side effects or toxicity. Well-known pharmaceuticals that have been in extensive use for years or decades show a wide range of optimal therapueutic potencies. Aspirin, for example, is often taken in multi-gram amounts per day for treatment of inflammation or arthritis, and detailed analyses of its mechanism of action in vitro show that a concentration in the millimolar range is required. In contrast, steroid-based topical anti-inflammatory compounds such as fluocinolone acetonide are many thousand-fold more potent, and, beyond this, some oral contraceptive agents are prescribed in daily doses in the micro- SUBSTITUTE SHEE gram range. Thus, although high potency is generally advantageous for a pharmaceutical, it is not an absolute requirement. Several thousand of the high skin-inflammatory and tumor-promoting phorboids have been reported in the literature, including numerous examples on which minor chemical modifications have been made [see Evans and Soper. Lloydia 41 193-233 (1978) and references cited therein]. The structures of these phorboids can be compared, and their activities for inflammation and tumor promotion can be analyzed from the perspective of efficacy and potency. The structures of the different classes of phorboids vary quite markedly from one to the other class (see Summary of the Invention for structural comparisons), yet widespread testing of their biological activities has shown that these classes have generally very similar biological properties. In particular, the thousands of known phorboids of the highly potent diterpene, indolactam, and polyacetate classes appear to have, with very minor exceptions, virtually identical efficacies as skin irritants and tumor promoters [T. Sugimura, Gann 73499-507 (1982)]. The exceptions involve a few compounds that have a short duration of irritant activity and/or manifest diminished tumor promoting activity, perhaps due to toxicity or secondary parameters such as differing metabolic destruction rates. In contrast to the essentially equal efficacies among the vast majority of phorboids, their relative potencies cover a wide range, as measured in inflammation and promotion tests and as measured in numerous other in vivo and in vitro systems. Example compounds can be found in the diterpene, indolactam, and polyacetate classes that have nearly equal, very high potencies. At the same time there are compounds in each of these classes which embody significant structural changes that do not diminish efficacy but do result in potency decreases of 10-fold to 100,000-fold or more [see, for example, Driedger and Blumberg. Cancer Res. 37 3257-3265 (1977), Cancer Res. 39 714-719 (1979)]. Thus, all these compounds appear to be capable of achieving generally the same biological results, and merely differ in the amount which must be used to obtain a given result. In vitro measurements of biochemical properties provide an even more sensitive method for comparing the properties of the various phorboids. For example, using a radioactively labeled phorboid such as [ 3 H]phorbol 12,13-dibutyrate or [^H]lyngbyatoxin, one can measure the potency of a test compound as a competitive ligand for the diacylglcerol binding site, which is also referred to herein as the "phorboid binding site" on protein kinase C or on other biological molecules which have phorboid binding sites (see below). Alternatively, one can measure the ability of a given phorboid to stimulate the protein kinase C-mediated incorporation of radioactive phosphate from [ ^P]adenosine triphosphate into a standard acceptor substrate such as histone HI. Tests of this nature reveal a difference in potency SUBSTITUTE S between given phorboid agonists of as much as 10,000,000-fold or more [Dunn and Blumberg, Cancer Res. 43 4632-4637 (1983), Table 1]. These basic data regarding the phorboid agonists are an important consideration because they underscore the concept that the structural differences among these previously known phorboids, especially the diterpenes, indolactams, polyacetates, and bryostatins, generally do not affect their efficacies as toxic agonists, and indeed a wide variety of structural changes are tolerated in this regard. Such changes generally alter potency only and do not provide agents with therapeutic utility, since they retain their toxicity. Some minor changes in phorboid structure are known to result in inactive compounds, such as a stereochemical change from 4-beta to 4-alpha in the phorbol series, and indeed some of the diterpene skeleton structures carry hydroxy groups that must be esterified in order for inflammatory activity to be observed. However, these inactive compounds are quite few in number among the known phorboids, and no therapeutic utility has been demonstrated for them. The phorbol esters, indolactams, polyacetates, diaminobenzyl alcohols, and bryostatins are generally found in plants, molds, and algae, or are synthetic in origin. Although they are found in many parts of the world, normal human contact with them is thought to be low. In contrast, the diacylglycerols are part of the functioning of virtually every type of animal cell except erythrocytes of some species, and thus the undesirable activation of protein kinase C by the diacylglycerols may have a very widespread role in human diseases. Thus, compounds capable of blocking the activation of, or inhibiting, protein kinase C by acting as specific pharmacological antagonists of the diacylglycerols at the diacylglycerol binding site on PKC, would be valuable agents in the prevention and treatment of a wide variety of diseases in animals and humans. For example, the need for, and potential utility of, PKC inhibitors/antagonists as agents for the treatment of cancer has received much attention [the "PKC inhibitors for cancer" article and maybe a P-170 MDR article]. PKC comprises a family of eight or more closely related protein molecules [Parker, PJ. et aJL. Mol. Cell. Endocrin. 65, 1-11 (1989)]. Because of their high degree of relatedness they are referred to as "isozymes", "isotypes" or "isoforms". Occasionally the term "subtypes" is used, but this term is usually reserved to designate, as a subdivision, two or more variants of a single isotype. The known isotypes of PKC are a, β-i , β^ an d Y (the "A-group"), ό, e ~ , e'[Ono, Y. et al.. J. Biol. Chem. 263. 6927-6932 (1988)], ζ, and the recently described "PKC-L" [Bacher, N. et al.. Mol. Cell. Biol. 11. 126-133 (1991)], also known as PKC?/ [Osada, S. et aL, J^ Biol. Chem. 265. 22434-22440 (1990)] (the "B-Group"). Members of the A- group require calcium ions for maximal activation, whereas the B-group members are SUBSTITUTE SHEET thought to be largely calcium-independent for activiation. The genes for each of the isotypes above have been cloned from one or more animal and yeast species and the clones have been sequenced; thus the relatedness of the genes and their product polypeptides is thus well established. A possible new, as-yet-unnamed member has also recently been described [Bignon, E. et aL, Biochem. Biophys. Res. Comm. 171, 1071- 1078 (1990)], but no DNA or protein sequence information is available to confirm the novelty of this PKC-like activity. It is possible that the different PKC isozymes have different biological roles, and published evidence supports this idea [Homan, E., Jensen, D. and Sando, J., J. Biol. Chem. 266. 5676-5681 (1991); Gusovsky, F. and Gutkind, S.. Mol. Pharm. 39. 124-129 (1991); Borner, C, 'The Role of Protein Kinase C in Growth Control", Sixth International Symposium on Cellular Endocrinology, W. Alton Jones Cell Science Center, Lake Placid, NY, August 12-15, 1990; Naor, Z. et aL, Proc. Natl. Acad. Sci. USA 86, 4501-4504 (1989); Godson, C, Weiss, B. and Insel, P., J. Biol. Chem. 265. 8369- 8372 (1990); Melloni, E. et aL, Proc. Natl. Acad. ScL USA 87, 4417-4420 (1990); Koretzky, G. et aL, J. Immunology 143. 1692-1695 (1989)]. For example, the stimulation of one PKC isotype or a limited subset of PKC isotypes might lead to undesirable results such as the development of inflammation [Ohuchi, K. et aL. Biochim. Biophys. Acta 925, 156-163 (1987)], the promotion of tumor formation [Slaga, T.. Envir. Health Perspec. 50. 3-14(1983)] or an increased rate of viral replication in cells (i.e., de novo infection of cells and/or expression, assembly and release of new viral particles) [Harada, S-et aL. Virology 154. 249-258 (1986)]. • On the other hand, other PKC isozymes might be responsible for the many beneficial effects observed when PKC is stimulated by known PKC activators in a variety of biological settings; such beneficial effects include the cessation of division of leukemic cells [Rovera, G., O'Brien, T. and Diamond, L.. Science 204. 868-870 (1979)], multiplication of colonies of lymphocytes [Rosenstreich, D. and Mizel, S.. J. Immunol. 123. 1749-1754 (1979)] and leucocytes [Skinnider, L. and McAskill. J.. Exp. Hematol. 8. 477-483 (1980)] or the secretion of useful bioregulatory factors such as interferon-y [Braude, I., U.S. Patent #4,376,822] and interleukin-2 [Gillis, S., U.S. Patent #4,401,756]. Recent publications indicate that diacylglycerol binding sites exist on newly- described proteins which lack the kinase domain, and thus lack the kinase activity, of protein kinase C. One such protein is n-chimaerin, found in human brain [Ahmed et al.. Biochem.J. 272. 767-773 (1990)] and and the other is the unc-13 gene product of the nematode Caenorhabditis elegans. [Maruyama, I. and Brenner, S., Proc. Natl. Acad. Sci. USA 88. 5729-5733 (1991)]. The presence of the diacylglycerol binding sites on these two proteins was demonstrated by standard binding experiments with [^HJphorbol 12,13-dibutyrate. These new proteins may have other enzymatic or SUBSTITUTE SHE biological activities which can be modulated by compounds which bind to their diacylglycerol binding sites. Thus, such compounds may have utility on non-protein kinase C biological targets. Given that there are now numerous distinct biological entities bearing diacylglycerol binding sites, it would be highly desirable to obtain chemical compounds which could specifically and selectively target one or another type of diacylglycerol binding site, thus permitting one to selectively activate or inhibit one such site without affecting the others. Such compounds would be valuable experimental tools for studying the role of individual types of proteins bearing diacylglycerol binding sites as well as providing novel means for treating diseases in which protein kinase C or other diacylglycerol binding site-bearing proteins are involved. There is one published report describing chemical compounds capable of selectively distinguishing several diacylglycerol/phorboid-type binding sites in mouse skin (Dunn and Blumberg, op. cit.). However, in this study, even the compounds showing the clearest differences in affinity for these distinct classes, namely phorbol 12,13-dibutyrate and 12-deoxyphorbol 13-isobutyrate, are only selective by a factor of 10-100 in dissociation constant among the different binding sites. However, these compounds have potent skin inflammatory activity and are not desirable in human or animal medicine because of this toxicity. Thus, to briefly recapitulate, two kinds of new compounds relating to diacylglycerol binding sites would be highly desirable. The first type would be capable of selectively activating one useful, but not another, deleterious, diacylglycerol target site. The second type would be capable of inhibiting, or antagonizing the stimulation of, one or more deleterious diacylglycerol binding site-bearing entities without blocking the useful ones. These kinds of compounds would be valuable agents for the study of diacylglycerol binding site-bearing entities and for the prevention or treatment of a wide range of human and animal diseases thought to involve protein kinase C or other entities under the control of diacylglycerol binding sites. Earlier efforts to use the previously known phorboids themselves or to modifiy of the structures of the known phorboids, have not been successful in producing useful compounds with toxicity low enough for use in humans. It has been known for some time that several of the toxic, inflammatory and tumor-promoting compounds such as phorbol 12-tigliate 13-decanoate, mezεrein, lyngbyatoxin and aplysiatoxin have anti-leukemic activity in mouse model tests [a couple of refs.]. However, these compounds are all extremely toxic and are cancer suspect agents, thus eliminating them from consideration as human therapeutic agents. Ganong et aL fProc. Nat. Acad. Sci. 83 1184- 1188 (1986)] tested a series of diacylglycerols and found no antagonistic activity in that series against the standard agonist 1,2-dioctanoylglycerol. It is of particular note that several compounds tested in SUBSTITUTE SHE this work were modified in the hydroxymethyl portion of the diacylglycerol molecule, and these modifications produced only a loss of activity or a weakened activity that was not distinguishable from the agonist activity of 1,2-dioctanoylglycerol itself, a compound which is toxic to mouse skin [ref. to tumor promotion or inflammation/hyperplasia]. These hydroxymethyl-modified compounds were not antagonists in these tests and no utility was found. Similarly, Thielmann and Hecker rForsch. Krebsforsch. Vol. VII. pp. 171-179 (1969), New York: Schattauer] found only a complete loss of biological activity in their study when the hydroxy group of the hydroxymethyl on phorbol 12,13 didecanoate was replaced with hydrogen or chlorine. Schmidt and Hecker [H. Lettre and G. Wagner (eds.), Aktuelle Probleme aus dem Gebiet der Cancerologie. Vol. Ill, 3rd Heidelberg Symposium, pp. 98-108. Berlin: Springer Verlag, 1971.] also found that oxidation of the hydroxymethyl of phorbol 12,13 didecanoate to a carboxylic acid caused complete loss of activity in the assays used. The hydroxymethyl group of the known phorboids (discussed in more detail in Summary of the Invention) has been thought to be required for biological activity, as detailed by Hecker (Hecker, E., Carcinogenesis. Vol. 2, eds. Slaga, Sivak and Boutwell, Raven Press, New York, 1978, pp. 11-48 and references cited therein). Indeed, it is stated therein that the replacement of the 20-hydroxyI in a phorbol ester "results in complete loss of biological activity". In another study, replacement of the hydroxy group of the hydroxymethyl (located at carbon 14) by chlorine or hydrogen in indolactam V gave rise to compounds with agonist activity weaker than but otherwise not distinguished from the agonist activity of the very toxic teleocidin class of tumor promoters [Irie et aL, Int. J. Cancer 36485-488 (1985)]. Thus no utility beyond that of the toxic, hydroxymethyl-bearing parent indolcatam-type compounds was found. Schmidt and Hecker (Carcinogenesis. Vol. 7, ed. by E. Hecker et aL, Raven Press, New York, 1982, pp. 57-63) studied the abilities of a series of diterpene phorboids to inhibit tumor promotion by the standard phorboid agonist tumor promoter phorbol 12-myristate 13-acetate (PMA). They found that, at low doses, some short-chain ester derivatives of phorbol were able to block the tumor promotion by PMA. However, all of the compounds that were active as antagonists at low doses are also very efficacious skin irritants themselves at higher doses and most of them are also known to have tumor promoting activity. Thus, these short-chain esters still have toxic inflammatory and tumor promoting activity and thus have no therapeutic value. Summary of the Invention In earlier work [cite EPO, and related patent applications], phorboids having novel chemical structures and diverse utilities as therapeutic agents and as tools for SUBSTITUTE SHEET biological research were described. These novel phorboids were derived from the previously known, toxic "parent" phorboids such as phorbol esters, indolactam V-based compounds, and so on, by replacement of the usual hydroxymethyl or 1-hydroxyethyl group of the parent phorboids with a diverse range of new chemical functionalities. These new functionalities embodied, however, a modest number of atoms in restricted structural forms and contained atoms of carbon, hydrogen, halogens, oxygen, nitrogen and sulfur, and phosphorus in a very restricted degree. The parent phorboid skeletons of these novel phorboids, that is, the regions of these molecules other than those which replaced the hydroxymethyl/ 1-hydroxyethyl groups of the parents, were also found to accomodate a very diverse range of structural elements, but again these structural elements were generally restricted to certain size limits and embodied only atoms of carbon, hydrogen, halogens, oxygen, nitrogen and sulfur. In the previous invention it is notable that in some cases the groups replacing the hydroxymethyl/1-hydroxyethyl moieties were somewhat larger than the hydroxymethyl/ 1-hydroxyethyl groups they replaced. In the present invention it has now been found that novel, biologically active and useful phorboids can result from the replacement of the usual phorboid hydroxymethyl/1-hydroxyethyl group with moieties of very much larger size than recognized previously. It has also been found now that new and useful compounds can be obtained when the hydroxymethyl/l-hydroxyethyl group of parent phorboids is replaced with moieties containing many heteroatoms beyond oxygen, nitrogen, sulfur, halogens, and certain placements of phosphorus. Thus, in the present invention the hydroxymethyl/l-hydroxyethyl group may be replaced with functionalities containing phosphorus in many locations, silicon, boron, selenium and arsenic. In this invention it has furthermore been found that the parent portion of hydroxymethyl/1-hydroxyethyl-modified phorboids may be substantially larger, may carry more substituents, may carry more of the previously permitted halogens and heteroatoms, may carry halogens in new positions, and may carry new heteroatoms selected from silicon and phosphorus, all without destroying the basic utilities of the resultant phorboids. Finally, in this invention it has been found that the diterpene- and indolactam- based phorboid parent radicals can comprise a wider range of specific structural features than previously recognized, again while maintaining the utilities associated with the alterations described for the hydroxymethyl/l-hydroxyethyl moieties. These observations thus extend greatly the variations which can be accomodated in both the moieties replacing the hydroxymethyl/l-hydroxyethyl groups and in the parent structures of hydroxymethyl/1-hydroxyethyl-modified phorboids in the previous invention cited above. SUBSTITUTE SHEET This invention pertains to novel phorboid derivatives which variously block the toxic effects of the hydroxymethyl-containing phorboids, lack the toxic properties of previously available phorboids and show activity for applications as therapeutics. The phorboid derivatives of the present invention embody very diverse structures and have utility as anti-inflammatory agents, as cancer cell and leukemic cell inhibitory agents, anti-asthmatic and anti-hypertensive agents, as modulators of human immune cell function, as anti-viral agents, as stimulators of the production of lymphokines such as interferon and the interleukins, as central nervous system pharmaceuticals for several pathological conditions, and as xenobiotics for achieving the control of parasites. The structural features associated with the non-toxicity and diacylglycerol binding site modulating properties of these compounds relate primarily to the hydroxymethyl or 1-hydroxyethyl group found in each of the toxic parent compounds. Specific modifications of the latter chemical groupings yields non-skin inflammatory compounds that show anti-inflammatory activity in several test systems, whereas any of a very wide variety of changes in other parts of the parent phorboid structures, including but not limited to diterpenes, indole alkaloids, polyacetates, diaminobenzyl alcohol derivatives, aplysiatoxins, and bryostatinoids, have very markedly less effect on the overall biological properties of the derivatives, other than changes in potency. This invention also provides new compounds that discriminate between phorboid receptor-type targets, with direct or imputed relative binding activities differing by 10,000-fold or more in some cases. A comparison of the structures of the previously known phorboids reveals the features that are critical for this invention, as shown below, in which the hydroxymethyl and 1 -hydroxymethyl groups are enclosed in dashed lines. TYPICAL DITERPENE- TYPE PHORBOID AGONISTS Phorbol 12- yristαte 13-Acetαte (PMA) SUBSTITUTE SHEET SUBSTITUTE SHEET TYPICAL DITERPENE-TYPE AGONISTS (Cont.) Phorbol 1 2— Retinoαte 1 3— Acetate Ingenol 3-Tetradecanoate TYPICAL DITERPENE- TYPE AGONISTS (Cont.) 15 ezerein GNIDIHACRIN 40 SUBSTITUTE SHEET TYPICAL DITERPENE-TYPE AGONISTS (Cont.) PJ MELEA FACTOR S 7 SUBSTITUTE SHEET TYPICAL INDOLACTAM- YPE PHORBOID AGONISTS Teleocidin Indolactam V 40 TYPICAL INDOLACTAM-TYPE PHORBOID AGONISTS (C ont. Blastmycetin A SUBSTITUTE SHEET TYPICAL DIAMINOBENZYL ALCOHOL-TYPE PHORBOID AGONISTS 3-Acetylamino-5-(N-decyl-N-methylamino)benzyl Alcohol 6-(N-decylamino)-4-hydroxymethylindole SUBSTITUTE SHEET TYPICAL DIACYLGLYCEROL-TYPE PHORBOID AGONISTS i) R^OLEOYL, R 2 =ACETYL if) R^STEAROYL, R 2 =ARACHID0N0YL iϋ) R ^R^OCTANOYL Typical Polyacetate-type Phorboid Agonists (Aplysiatoxin and its debromo, bromo, and dibromo derivatives) SUBSTITUTE SHEET TYPICAL BRYOSTATIN-TYPE PHORBOID AGONISTS SUBSTITUTE SHEET TYPICAL BRYOSTATIN-TYPE PHORBOID AGONISTS (Cont.) SUBSTITUTE SHEET It can be seen that the phorboids depicted have diverse structural elements of both hydrophilic and hydrophobic nature, with one prominent exception, namely that each contains a hydroxymethyl or 1-hydroxyethyl group (indicated by the dashed-line boxes in each structure). In each case the phorboid depicted is among the most potent of its particular structural class, and among the classes the diterpenes, indolactams and polyacetates have members of especially high potency. The hydroxymethyl and 1-hydroxyethyl feature common to all the classes of phorboids is the primary focus of this invention, in which the variations which can be accomodated in the moieties replacing the hydroxymethyl/l-hydroxyethyl groups are found to include new heteroatoms and to be larger and more complex than previously recognized. Furthermore, the parent structures of hydroxymethyl/1-hydroxyethyl- modified phorboids have now also been found to tolerate larger and more complex structural features and more kinds of heteroatoms than previously recognized. Generally the phorboid derivatives of this invention can be represented by the formula: P - G wherein P represents a radical, formally derived from a parent compound, which compound: a. binds reversibly or irreversibly to a diacylglycerol-type receptor; and/or b. activates any form of the enzyme protein kinase C; and c. contains an hydroxymethyl or 1-hydroxyethyl group bonded to a carbon atom; and wherein G is any group of 55 or fewer atoms selected from carbon, hydrogen, oxygen, nitrogen, halogen, sulfur, phosphorus, silicon, arsenic, boron and selenium either i) singly or doubly bonded to the carbon atom of the parent compound in place of the hydroxymethyl or 1-hydroxyethyl group; or ii) singly or doubly bonded to a carbon atom immediately adjacent to the carbon atom to which the hydroxymethyl or 1- hydroxyethyl group is bound in the parent compound; and wherein the hydroxymethyl or 1-hydroxyethyl group of the parent compound is absent or has been replaced by G. More specifically, the compounds of this invention are represented by the formula: V *o which depicts a phorboid "parent" compound radical P Q modified by a moiety S Q E 0 . In general, a parent compound is a compound which: a. binds reversibly or irreversibly to a diacylglycerol-type receptor; and/or TUTE SHEET b. activates any form of the enzyme protein kinase C; and c. contains an hydroxymethyl or 1-hydroxyethyl group bonded to a carbon atom. For example, a parent compound can be a diterpenoid activator of protein kinase C; an aromatic heterocyclic activator of protein kinase of the indole, indene, benzofuran, or benzothiophene class, further defined here by the presence of a substituted or unsubstituted six-atom chain connecting positions 3 and 4 of the indole, indene, benzofuran or benzothiophene to form an additional 9-membered ring; a polyacetate- derived activator of protein kinase C; an activator of protein kinase C of the diacylglycerol or diacyloxybutanol class; an activator of protein kinase C of the diaminobenzyl alcohol class; or a protein kinase C activator of the bryostatin class. S 0 -E 0 represents a modifying moiety which is either: i)singly or doubly bonded to the carbon atom of the parent compound Po in place of the hydroxymethyl or 1-hydroxyethyl group; or ii)singly or doubly bonded to a carbon immediately adjacent to the carbon atom to which the hydroxymethyl or 1-hydroxyethyl is bonded. In the S 0 -E 0 moiety, S Q can be a substituted or unsubstituted, saturated, unsaturated and/or aromatic, straight or branched, acyclic, ring-containing and/or ring-carrying chain of atoms which separates P Q and E Q by a linear count of at least two but not more than 12 atoms and contains and/or carries not more than 9 heteroatoms selected from oxygen, nitrogen, silicon, sulfur, phosphorus, arsenic, boron and selenium, and not more than 16 halogen atoms; provided that the total number of atoms does not exceed 35; and in some cases S Q may be a single or double bond; and E Q can be hydrogen, halogen or a saturated or singly or multiply unsaturated group containing up to 15 carbon atoms and optionally containing 1 to 12 halogen atoms and/or 1 to 6 heteroatoms selected from oxygen, nitrogen, silicon, sulfur, phosphorus, arsenic, boron and selenium. S Q E 0 taken together may also be a hydrogen, halogen, thionic sulfur atom or ketonic oxygen atom or a hydroxy, amino, or thiol group singly or doubly bonded to the carbon atom of the parent compound P Q in place of the hydroxymethyl or 1-hydroxyethyl group. Detailed Description of the Invention All six classes of the known phorboids have one structural element in common. Each prototypical member of these classes has either a hydroxymethyl group or a 1- hydroxyethyl group. The design of the phorboid derivatives of this invention is based on the finding that the hydroxymethyl and 1-hydroxyethyl groups, which previously were thought to be required for biological activity of phorboids containing these groups, can be replaced by other substituents of very diverse nature, even though these new substituents are very substantially larger and of more diverse structure and SUBSTITUTE SHEET heteroatom composition than the original hydroxymethyl/l-hydroxyethyl group. For example, the hydroxymethyl group of a typical diterpene phorboid such as phorbol- 12-myristate 13-acetate may even be replaced by a tetracyclic moiety containing some 36 carbon atoms, to form the dimeric molecule Phorbol 12-Myristate 13-Acetate 20,20'-bis-deoxy-dimer which still exhibits diacylglycerol site binding activity and anti-viral properties. The compounds resulting from the hydroxymethyl changes described here variously block the toxic effects of the hydroxymethyl-containing phorboids, lack the skin-inflammatory properties associated with the previously available phorboids and show useful activity as therapeutic agents. These new compounds thus have utility as, variously, anti-inflammatory agents, anti-viral agents and anti-leukemic agents, for example. Although the replacement of the hydroxymethyl group or 1-hydroxyethyl group is very specific and leads to an extreme and profound change in biological properties, a wide range, much wider than previously recognized, of structural alterations in the non-hydroxymethyl/1-hydroxyethyl portions of the novel compounds can be tolerated without material loss of their basic, favorable biological properties. The phorboid derivatives of this invention are generally represented by the formula: P - G The-formula depicts a radical, P, derived from a parent compound, which compound: a. binds reversibly or irreversibly to a diacylglycerol-type receptor; and/or b. activates any form of the enzyme protein kinase C; and c. contains an hydroxymethyl or 1-hydroxyethyl group bonded to a carbon atom; and wherein G is any group of 55 or fewer atoms selected from carbon, hydrogen, oxygen, nitrogen, halogen, sulfur, phosphorus, silicon, arsenic, boron and selenium either i) singly or doubly bonded to the carbon atom of the parent compound in place of the hydroxymethyl or 1-hydroxyethyl group; or ii) singly or doubly bonded to a carbon atom immediately adjacent to the carbon atom to which the hydroxymethyl or 1- hydroxyethyl group is bound in the parent compound; and wherein the hydroxymethyl or 1-hydroxyethyl group of the parent compound is absent or has been replaced by G. More specifically, the phorboid derivatives of this invention are represented by the formula: ^o " ^o " E o The formula depicts a radical P 0 , formally derived from a parent hydroxymethyl- containing phorboid compound, bonded to an S Q -E 0 moiety. P 0 represents a radical formally derived from a compound which contains an hydroxymethyl (or the equivalent 1-hydroxyethyl) group and which binds reversibly or irreversibly to a diacylglycerol-type receptor and/or activates any form of the enzyme protein kinase C. P Q may be formally derived from phorboids from any of the six classes listed below: i) a diterpenoid activator of protein kinase C; ii) an aromatic heterocyclic activator of protein kinase of the indole, indene, benzofuran, or benzothiophene class; iii) a polyacetate-derived activator of protein kinase C; iv) an activator of protein kinase C of the diacylglycerol or diacyloxybutanol class; v) an activator of protein kinase C of the diaminobenzyl alcohol class; and vi) a protein kinase C activator of the bryostatin class. All of these phorboids contain an hydroxymethyl or 1-hydroxyethyl group which is known to be associated with their toxic biological activity, such as skin inflammatory activity measured on the mouse ear. S 0 -E 0 represents a moiety which is either: i) singly or doubly bonded to the carbon atom of the parent compound in place of the hydroxymethyl or 1-hydroxyethyl group; or ϋ) singly or doubly bonded to a carbon immediately adjacent to the carbon atom to which the hydroxymethyl or 1-hydroxyethyl group is bound in the parent compound. In this S 0 -E 0 moiety, S Q can be a substituted or unsubstituted, saturated, unsaturated and/or aromatic, straight or branched, acyclic, ring-containing and/or ring-carrying chain of atoms which separates P Q and E Q by a linear count of at least two but not more than 12 atoms and contains and/or carries not more than 9 heteroatoms selected from oxygen, nitrogen, silicon, sulfur, phosphorus, arsenic, boron and selenium, and not more than 16 halogen atoms; provided that the total number of atoms does not exceed 35; and in some cases S Q may be a single or double bond; and E Q can be hydrogen, halogen or a saturated or singly or multiply unsaturated group containing up to 15 carbon atoms and optionally containing 1 to 12 halogen atomsand/or 1 to 6 heteroatoms selected from oxygen, nitrogen, silicon, sulfur, phosphorus, arsenic, boron and selenium. S 0 E 0 taken together may also be a hydrogen, halogen, thionic sulfur atom or ketonic oxygen atom or a hydroxy, amino, or thiol group singly or doubly bonded to the carbon atom of the parent compound P Q in place of the hydroxymethyl or 1-hydroxyethyl group. In a preferred embodiment, the phorboid derivatives of this invention are represented as follows: P„ - S v - E 1 wherein P χ can be selected from six different classes of compounds designated Pi-Pg and defined b.elow, wherein S χ is selected from seven different structural types as defined below and E j is as defined below. P j _, Pg, P3, P4, P5, and P β represent compounds of each of the six classes of known SUBSTITUTE SHEET in the form of an individual isomer, an isomer mixture, a racemate or optical antipode, or a pharmaceutically acceptable salt thereof; wherein A* and A-" may be independently selected from hydrogen, halogen and a substituent having not more than 34 carbon atoms, not more than 24 halogen atoms and not more than 9 heteroatoms selected from oxygen, nitrogen, silicon, phosphorus and sulfur, or A ~ and A* taken together may complete a 5- or 6-membered saturated or unsaturated carbocyclic or heterocyclic ring, optionally substituted by 1-8 halogens and/or other groups, which halogens and groups taken together contain a total of not more than 30 carbon atoms, not more than 24 halogen atoms and not more than 9 heteroatoms selected from oxygen, nitrogen, silicon, phosphorus and sulfur; A^ is a three atom chain which carries S χ E j and completes a 7-membered saturated or unsaturated carbocyclic ring optionally substituted by 1-6 halogens and/or other groups, which halogens and groups taken together, excluding S χ E j , contain not more than 12 carbon atoms, not more than 8 halogen atoms, and not more than 5 heteroatoms selected from oxygen, nitrogen, silicon, phosphorus and sulfur; provided that, including S χ E j , the middle carbon atom of A is not substituted by hydroxymethyl or 1-hydroxyethyl; A* completes a 6- or 7-membered carbocyclic or heterocyclic ring which is connected in the ? configuration to either carbon atom 9 or 10 and carries an 11 -methyl group in the or ? configuration, wherein A 4 is optionally substituted further by 1-10 halogens and/or other groups, the group or groups optionally completing 1-3 additional rings through bonds among themselves and/or 1-5 additional rings when taken together with A , A^, a ring formed by A- and A^ together, and/or a bond to carbon atom 9, which halogens and groups taken together include not more than 40 carbon atoms, not more than 24 halogen atoms, and not more than 15 heteroatoms selected from oxygen, nitrogen, silicon, phosphorus and sulfur; J 1 is hydrogen, fluoro, chloro, hydroxy, amino, mono- or di-loweralkylamino, methyl, ethyl, vinyl, ethynyl, propargyl, cyano, methoxy, ethoxy, trifluoromethyl, 2-hydroxyethyl, 2-hydroxypropyl, 3-hydroxypropyl, acetoxy, propanoyloxy, acetyl, propanoyl, hydroxyacetyl, 2-hydroxypropanoyloxy, 3- hydroxypropanoyl, acetamido, propanamido, hydroxyacetamido, 2- hydroxypropanamido, or 3-hydroxypropanamido, (each of which must be situated in the beta position), or J taken together with A , A , A or a ring formed by A^ together with A^ completes a 3- to 7-membered substituted or unsubstituted carbocyclic or heterocyclic ring, the substituents of which contain not more than 15 carbon atoms, not more than 10 halogens, and not more than 8 heteroatoms selected from oxygen, nitrogen, silicon, phosphorus and sulfur; Jp is selected from hydrogen, methyl, ethyl, hydroxymethyl, hydroxyethyl, vinyl, ethynyl, allyl, propargyl, n-propyl and isopropyl; SUBSTITUTE SHEET provided that, if A and A^ are not linked to form a ring, A must carry a cyclopropyl at positions 13 and 14; the total P j ring skeleton may not comprise any of the following six frameworks, which are derived from various homo-, nor- and homo-nor- steroids: and provided that: for all P j , when are S χ E j taken together and bonded to carbon 6, they may not comprise — CHg, — CH=O, — CH2θ-R es wherein R es is an acyl group, — CH θ-R et wherein R et is a C^-Cg hydrocarbon radical or is -C^Hg^O-linked via the oxygen atom to carbon 5 of Pi , is a nitrophenyl ring optionally bearing additional substituents; P^S χ E j may not include 12-beta-13- alpha-diacetoxy derivatives of compounds having the exact 20-carbon tigliane or 19- carbon 20-nor-tigliane skeleton; P j S χ E^ may not comprise 20-deoxy-20- chlorocrotophorbolone nor 20-deoxy-20-chlorophorbol 12,13-diesters wherein the ester groups are both selected from saturated or unsaturated alkanoyl or are both benzoyl; if bonded to carbon 6, P j may not carry a ring formed by — OC(CH3)2O- j - bonded in the beta configuration to carbons 3 and 4; and P j S χ E j may not comprise 6-deshydroxymethyl-6-carboxyphorbol 12,13-didecanoate or 6- deshydroxymethyl-6-carboxyphorbol 12, 13-diacetate; P2 is a radical of the formula: in the form of an individual isomer, an isomer mixture, a racemate or optical antipode, SUBSTITUTE SH or a pharmaceutically acceptable salt thereof, wherein B - completes a 6-membered carbocyclic or heterocyclic aromatic ring, optionally substituted by halogen/s and/or other groups, which halogens and groups taken together contain not more than 40 carbon atoms, not more than 24 halogen atoms, and not more than 9 heteroatoms selected from oxygen, nitrogen, silicon, phosphorus and sulfur, the groups being optionally connected to one another and/or to B2 to form 1-3 additional rings; B^ is selected from oxygen, sulfur, sulfoxide, sulfone, monofluoromethylene, difluoromethylene, and a carbon or nitrogen atom optionally substituted by groups having not more than 15 carbon atoms, not more than 24 halogen atoms, and not more than 6 heteroatoms selected from oxygen, nitrogen, silicon, phosphorus and sulfur, and B^ may be linked to B or K j to form an additional carbocyclic or heterocyclic ring; K s hydrogen, halogen or a group containing not more than 15 carbon atoms, not more than 18 halogen atoms, and not more than 6 heteroatoms selected from oxygen, nitrogen, silicon, phosphorus and sulfur, and K* may be linked to B* or B 3 or to both B^ and B^ to form one or more additional carbocyclic and/or heterocyclic rings; B° is a 2-carbon chain optionally substituted by halogen/s and/or one or more groups which, taken together but excluding S χ E^, contain not more than 12 carbon atoms, not more than 6 halogen atoms, and not more than 6 heteroatoms selected from oxygen, nitrogen, and sulfur; provided that, including S χ E j , the carbon atom of B^ bonded to K as defined below does not carry — CH2OH or — CHCH3OH; K is selected from oxygen, sulfur --NK - or — CK"K '-- wherein K" is hydrogen, hydroxy, methyl, ethyl, fluoro, n-propyl, allyl, or propargyl, and K' is hydrogen, methyl, ethyl, halogen, trifluoromethyl or cyano; K^ and K 4 may be the same or may differ and each may independently be hydrogen, halogen, a substituent group, or may complete an additional ring connecting K 3 and K 4 or connecting either K3 or K to K 5, such that Kr and K 4 taken together contain not more than 18 carbon atoms, not more than 24 halogen atoms, and not more than 6 heteroatoms selected from oxygen, nitrogen, silicon, phosphorus and sulfur; K is selected from oxygen, sulfur, sulfoxide, sulfone or ~NK 8 ~, --NOK 8 -- or — CK 8 K 9 — wherein K 8 is hydrogen or a group containing not more than 30 carbon atoms, not more than 24 halogen atoms, and not more than 8 heteroatoms selected from oxygen, nitrogen, silicon, phosphorus and sulfur, and K 9 is hydrogen, methyl, ethyl, n-propyl, hydroxy, halogen, allyl, propargyl, cyano, or trifluoromethyl; provided that P S χ E j may not comprise (-)- 1,10,14-0- trimethylindolactam V, and provided that if B completes an unsubstituted or substituted carbocyclic aromatic ring, and B* is — NH— , — N-^ j -C 1 ^ linear or branched alkyl or alkanoyl)— , — N- COOCH 2 C 6 H 5 — or — N-COO(CH 3 ) 3 — , and SUBSTITUTE SHEET K is hydrogen, and K 2 is — NH— , and K is hydrogen, and K 5 is — NH— or — N(C r C3-alkyl)— , then (i) if S χ E j is bonded to the carbon atom in B that is adjacent to K , then S χ Eιmay not be — COOMe or — COOEt; and (ii) if S χ is a single bond directed to the carbon atom in B 3 that is adjacent to K and E j is — CH2 — R|, then R| is not any of hydrogen, chloro, bromo, C j -C j 2 saturated or unsaturated linear or branched alkoxy, CH OCH O — , Cι-Cι 2 linear or branched alkanoyloxy, bromoacetoxy, benzoyloxy, azidobenzoyloxy, 3,5-(CH3)2-CgH3COO — , methanesulfonyloxy, toluenesulfonyloxy, dansyloxy, (tetrahydro-2H-pyran-2-yl)oxy, or (C j -C6 linear or branched alkyI) n (phenyl)3_ n silyloxy, wherein n is 0-3; P3 is a radical of the formula: in the form of an individual isomer, an isomer mixture, a racemate or optical antipode, or a pharmaceutically acceptable salt thereof, wherein L 1 , L 2 and L 3 are individually SUBSTITUTE SHEET selected from nitrogen or substituted or unsubstituted carbon; D* and D^ each may be a bond or a substituted or unsubstituted carbon atom; O- may be linked to L , Lr or both L and Lr to form additional fused carbocyclic and/or heterocyclic substituted or unsubstituted rings; and D may be linked to L , L 3 or both L^ and L 3 to form additional fused carbocyclic and/or heterocyclic substituted or unsubstituted rings; D° and D 4 each are heteroatom-containing functional groups, the heteroatoms being selected from oxygen, nitrogen, silicon, phosphorus and sulfur; D may be linked to L , r or both L and Lr to form additional fused substituted or unsubstituted carbocyclic and/or heterocyclic rings; and D 4 may be linked to Lr, L 3 or both Lr and L 3 to form additional fused substituted or unsubstituted carbocyclic and/or heterocyclic rings; provided that D and D 3 taken together and D^ and D 4 taken together both embody at least one oxygen, nitrogen, silicon, phosphorus or sulfur atom separated from the aromatic nucleus by zero or one intervening carbon atom; and L 4 and Lr are groups which, taken together, contain about 2-40 carbon atoms, not more than 24 halogen atoms, and not more than 6 heteroatoms selected from oxygen, nitrogen, silicon, phosphorus and sulfur; provided that S 0 E 0 may not be hydroxymethyl or 1- hydroxyethyl. P^ is a radical of the formula: in the form of an individual isomer, an isomer mixture, a racemate or optical antipode, or a pharmaceutically acceptable salt thereof, wherein V- is a bond or is a carbon atom carrying substituents individually selected from hydrogen, methyl, and halogen; V 2 and V 3 are individually selected from oxygen, sulfur, sulfoxide, and --NV 4 — in which V 4 is hydrogen or a hydrocarbon radical containing not more than 30 carbon atoms; F ~ and F^ independently are groups which, taken together, contain 10-40 carbon atoms, not more than 24 halogen atoms, and not more than 8 heteroatoms selected from oxygen, nitrogen, silicon, phosphorus and sulfur, and wherein F^ and F 2 may optionally be linked to form a structure comprising 1-3 rings; F 3 is hydrogen or a TITUTE HEET substituent selected from methyl, ethyl, trifluoromethyl, 2,2,2-trifluoroethyl, cyano, vinyl, ethynyl, allyl, and propargyl; F 4 and F 5 each may be hydrogen or may be hydrocarbon or halogenated hydrocarbon radicals which, taken together, contain not more than 40 carbon atoms, not more than 24 halogen atoms and not more than 8 heteroatoms selected from oxygen, nitrogen, silicon, phosphorus and sulfur, and wherein F 4 and F^ may optionally be linked to form a structure comprising 1-3 rings; provided that V 4 , F , F 2 , F 4 and F 5 taken together contain not more than 50 carbon atoms, not more than 30 halogens and not more than 12 heteroatoms selected from oxygen, nitrogen, sulfur, silicon and phosphorus; and provided that S χ E j may not be hydrogen, methyl, chloromethyl, hydroxymethyl, mercaptomethyl, unsubstituted carboxamido, 1-hydroxyethyl or alkanoyloxymethylene; P5 is a radical of the formula: in the form of an individual isomer, an isomer mixture, a racemate or optical antipode, or a pharmaceutically acceptable salt thereof, wherein U and U , independently, are selected from hydrogen, azide, halogen, hydroxy, Cγ_η alkoxy, Ci.y alkenoxy, Cμy alkynoxy, thiol, C j .7 alkanoyl, Cγ j saturated or unsaturated alkyl, and cyano; or U* and U Λ taken together may be an oxygen atom forming an epoxy group or may be an ' additional bond forming an unsaturated linkage; U 3 is selected from hydrogen, halogen, Cμ^ alkyl, Cj-C^ alkenyl, Cj-C^ alkynyl, C j -C^ alkoxy, C j -C^ alkenoxy, Cj-C^ alkynoxy, and aryl or C- -C^ aralkyl wherein the aryl group may be substituted by nitro, halogen, cyano, and/or diloweralkylamino groups; U 4 -U^, SUBSTITUTE SHEET independently, are selected from hydrogen, halogen, cyano, nitro, amino, diloweralkylamino, C j .y saturated or unsaturated alkyl, hydroxy, C j .y saturated or unsaturated alkoxy, C^.7 carboalkoxy, C _> j alkanoyloxy, and azide; and U 7 is selected from hydrogen, Cγ_η saturated or unsaturated alkyl, and C j . saturated or unsaturated alkanoyl; provided that if S 0 E 0 is hydroxymethyl, 1-hydroxyethyl or acetoxymethylene, then S 0 E 0 may not be bonded to C2g- Pg is a radical of the formula: in the form of an individual isomer, an isomer mixture, a racemate or optical antipode, or a pharmaceutically acceptable salt thereof, wherein W is selected from hydrogen, halogen, hydroxy, C j .g alkoxy, C j .g alkanoyloxy and cyano; W* is selected from oxo, hydrogen, hydroxy, cyano, C j .y alkyl, C j .y alkoxy, C j .y alkanoyloxy, and halogen; W -W 5 each may be hydrogen or a group containing not more than 30 carbon atoms, not more than 24 halogen atoms, and not more than 8 heteroatoms selected from oxygen, nitrogen, and sulfur, and W 4 and W 5 taken together may form an additional carbocyclic or heterocyclic ring; W 6 is hydrogen or a group containing not more than 15 carbon atoms, not more than 12 halogen atoms and not more than 5 heteroatoms selected from oxygen, nitrogen, and sulfur; and W 6 , taken together with W 4 and W^, may complete an additional carbocyclic or heterocyclic ring; provided that if S 0 E 0 is SUBSTITUTE SHE hydroxymethyl or hydroxyethyl then S Q E 0 may not be bonded to C25. S χ may represent any of a broad range of connecting chains or groups of atoms, designated S β , Si , S2, S3, S4, Sg and Sg. Surprisingly, these moieties may be hydrophobic in nature, with few if any polar or heteroatoms present, may be extensively halogen-substituted, or may contain one or several polar atoms such as oxygen, nitrogen, silicon, phosphorus, arsenic, boron selenium and/or sulfur in any of numerous chemical groupings. Such functional groupings may even bear positive or negative charges at physiologic pH, and the values which are permissible for S χ also may include combinations of hydrophobic, halogenated, hydrophilic and/or charged functional groups. The resultant compounds in any case generally display, variously, the protein kinase C-modulatory, non-toxic agonist, and/or antagonistic properties, selectivities and utilities described in this invention. In a preferred mode of this invention, Sg-Sg may comprise the following values. wherein a, b, d, e, and g may independently be from 0 to 3; c and f may independently be 0 or 1; the sum of (a+b+c+d+e+f+g) is at least 1 but not more than 12; and if c SUBSTITUTE SHEET and fare both 1, then the sum of (d+e) must be at least 1; and X and X' are as defined below. wherein h, i, k, m, p, and q may be independently be from 0 to 3; j and n may independently be 0 or 1; ifj and n are both 1 and 1 is 0, then the sum of (k + m) must be at least 1; if n is 1 and o is 0, then the sum of (p + q) must be at least 1; the sum of (1 + o) is 1-3; and the sum of (h+i+j+k+21+m+n+2o+p+q) is at least 1 but not more than 12; and X, X', Y and Y' are as defined below. S3 is a chain of atoms of the formula: SUBSTITUTE SHEET wherein r, s, u, y, a', and b' may independently be from 0 to 3; the sum of (t + z) is 0 or 1; the sum of (v + w + x) is 1; the sum of (y + z + a' + b') is at least 1; and the sum of (r + s + 2t + u + 2v + 3w + 4x + y + 2z + a' + b') is at least 1 but not more than 12; and Y, Y', Z 1 , Z 2 , and Z 3 are as defined below. S4 is a chain of atoms defined by: SUBSTITUTE SHEET wherein c\ d', e', h', and i' may independently be from 0 to 3; the sum of (f + g') must be 1 or 2; f and g' may independently be 0 or 1; and the sum of (c' + d' + e' + f + g' + h' + i') is at least 1 but not more than 12; and M, M', and R S are as defined below. Sf j is a chain of atoms defined by: SUBSTITUTE SH wherein j', k', m', q', and s' may independently be from 0 to 3; 1' and r' may each be 0 or 1, but the sum of (1' + r') must be 1 or 2; n' and p' may each be 0 or 1, but the sum of (n' + p') must be 0 or 1; the value of o' may be 0-2; if the sum of (n' + p') is 1 and 1' is 0, then q' must be at least 1; if the sum of (n' + p') is 1 and r' is 0, then m' must be at least 1; and the sum of (j' + k' + 1' + m' + n' + o' + p' + q' + r' + s') is at least 1 but not more than 12; and , Q', X, X', and Y are as defined below. Sg is a chain of atoms defined by: SUBSTITUTE SHEET 40 SUBSTITUTE SHEET wherein u', v', w', x', y', z', and m" may each be 0 or 1; t' and a" may each independently be 0-6; the sum of (t' + u' + v' + 2w' + X' + 2y' + z' + a") must be 0-8; b", d", e", f", h", j", k" and n" may each independently be 0 or 1; c", g", i", and 1" may each independently be 0-3; if d" andj" are both 1, then the sum of (g" + i") must be at least 1; if either j" or k" is 1, then 1" must be at least 1; if b" is 1, then the sum of (c" + g" + h" + i" + 1") must be at least 1; if d" is 1, then the sum of (g" + h" + i" + 1") must be at least 1; and the sum of (t' + u' + v' + 2w' + x' + 2y' + z' + a" + b" + c" + d" + e" + 2f" + g" + 2h" + i" + j" + k" + 1") must be 0-14; if m" is zero, R§ or R$ may optionally comprise an additional bond to G-" as defined below, thus completing an unsaturated linkage; if n" and b" are zero, Rg or Rg may optionally comprise an additional bond to G , thus completing an unsaturated linkage; one of the substituents Rg-Rg and/or one of the substituents RgRβ^may optionally comprise the same or different values of G 1 , as defined below; and M, M\ Q, ', Q", Q"\ X, X', X", Y, Y', Z , Z 4 , 7r and 7? are as defined below; and wherein, for S i -Sg, Rj through R^may be the same or different and each may be hydrogen, halogen or an acyclic substituent containing not more than 20 carbon atoms, not more than 16 halogen atoms, and not more than 6 heteroatoms selected from oxygen, nitrogen, sulfur, silicon and phosphorus; one substituent selected from R}, Rf , R 2 , R§, Rj, 2 3, R-4, R 2 R X 5, R 2 5, R X g and R 2 6 may optionally comprise an additional bond completing an unsaturated linkage to P^; one or two of alues of G , additonal bond to E j , thereby completing an unsaturated linkage; one of the substituents Rj-R^ may be linked to either the atom in P χ that carries the S j chain or to an atom in P χ adjacent thereto, to form a 4-8 membered ring optionally containing 1-4 identical or different ring hetero members selected from X and =N-, the ring being optionally substituted by 1-8 identical or different substituents, preferably selected from halogen, hydroxy, methoxy, ethoxy, methyl, ethyl, cyano, azide, nitro, hydroxymethyl, 1-hydroxyethyl, 2-hydroxy-2-propyl, CF3, OCF3, SH, SCH3, SOCH3, SCF3, COOH, COOCH3, COCH3, CH=O, acetoxy, amino, mono- or dialkylamino totalling 1-4 carbon atoms inclusive, acetamido, N-methylacetamido, carboxamido, N-alkylated carboxamido containing 1-4 carbon atoms inclusive, hydroxyacetyl and hydroxyacetoxy; provided that, for any given S j , S2, S3, S4, S5 or Sg, but excluding P χ and E j : the total of carbon atoms is 25 or less; the total of halogen atoms is 16 or less; the total of oxygen atoms is 6 or less; the total of nitrogen atoms is 4 or less; the sulfur, silicon and SUBSTITUTE SHEET phosphorus atoms each total 3 or less; and the total of oxygen, nitrogen, silicon, phosphorus and sulfur atoms together is 8 or less. In a preferred mode of this invention, the oxygen, nitrogen, sulfur, silicon and/or phosphorus atoms in Rj-Rg 2 may be situated in a variety of functional groups such as hydroxy, amino, hydroxylamine, tertiary amine oxide, SchifFs base, hydrazine, thiol, nitro, nitroso, oxime, azide, ether, acetal, ketal, thioether, aldehyde, keto, hydrazone, carboxy, mercaptocarbonyl, mercaptothionocarbonyl, sulfonate, sulfonyl, sulfoxide, phosphate, phosphonate, phosphate ester, phosphonate ester, phosphine, phosphine oxide, thionophosphine, phosphite, phosphonium, phosphorothioate, thionophosphate ester, thiophosphonate, thionophosphonate ester, silane, silanol, silanediol, fluorinated silane, ester, amide, cyano, hydrazide, carbonate, carbamate, urea, isourea, carboxamidine, imidate, guanidine, thioester, thioamide, thiocarbonate, dithiocarbonate, thiocarbamate, dithiocarbamate, thiourea, isothiourea, thioimidate, nitroguanidine, cyanoguanidine and xanthate. Preferably, for any given S χ , the total of — NH2 groups is 2 or less, the total of-SH groups is 2 or less, and the total of -OH, — SH and — NH2 groups is 4 or less. X, X', X" may be the same or different and are selected from: 0 Q — Ch — — s — — " S — — n s — I I 0 SUBSTITUTE SHEET wherein R , R ξ, R ^and R ^ may independently be hydrogen; R through Rjr may be the same or different and each may be an acyclic substituent containing 1-20 carbon atoms, not more than 16 halogen atoms, and not more than 6 heteroatoms selected from oxygen, nitrogen, and sulfur, such that for any substituent the oxygen atoms total 4 or less, the nitrogen atoms total 4 or less, and the sulfur atoms total 2 or less; Rχ 5 Rχ » R^ and R ^-may independently be hydroxy; and Q' are as defined below; jζ may optionally represent an additional bond to P χ , thus completing an unsaturated linkage; one or two of the substituents Rχ-Rχ^ may optionally comprise the same or different values of G , as defined below; Y and Y' may be the same or different and are selected from: — c=c — - — c— c — wherein R.γ and Rγ t and RΫ and Rγ 5 each pair being cis or trans relative to one another, may be the same or different and each may be hydrogen or an acyclic substituent containing not more than 20 carbon atoms, not more than 16 halogen atoms, and not more than 6 heteroatoms selected from oxygen, nitrogen, and sulfur, such that for any substituent the oxygen atoms total 4 of less, the nitrogen atoms total 4 or less, and the sulfur atoms total 2 or less; R-^ and Ry may also independently be halogen; one or two of the substituents Rγ-Rγ may optionally comprise the same or different values of G , as defined below; and one of the substitents Rχ-R ^ and Rγ-Rγ may be linked to either the atom in P χ that carries the chain containing X, X', and/or X" or to an ' atom in P χ adjacent thereto, to form a 4-8 membered ring defined as for the analogous R j -Rg -containing ring above. In a preferred embodiment, the substituents Rχ-Rχ^ and Ry-Rγ are selected from hydroxy, amino, thiol, nitro, azide, ether, thioether, aldehyde, keto, carboxy, mercaptocarbonyl, mercaptothionocarbonyl, sulfonate, sulfonyl, sulfoxide, ester, amide, cyano, carbonate, carbamate, urea, isourea, carboxamidine, guanidine,. thioester, thioamide, thiourea, nitroguanidine, cyanoguanidine and xanthate. SUBSTITUTE SHEET Z is selected from: 15 Tr is selected from: -C=N— N — N— N=C — ^ 11 z 2 k 2 k 4 25 -C=N— O — NzzC— R z 5 R 2 6 Z is selected from: 5 0 SUBSTITUTE SHEET Z 4 and Z 4 independently may be: ■ N- Tp and T independently may be: o r O— N wherein the substituents R-^-R^ are generally selected from hydrogen, halogen in cases where a chemically stable sstructure results, and a radical containing about 1-12 carbon atoms and optionally containing 0-12 halogens and 0-6 heteroatoms selected from oxygen, nitrogen and sulfur. In a preferred embodiment of the invention, the substituents R-^-R^ comprise a range saturated or unsaturated substituents as described below, wherein the terms alkyl, halogenated alkyl and acyl are taken to include alkenyl, alkynyl, alkenoyl and alkynoyl and their halogenated forms. Thus: R be any of the values specified for Rχ-R above; R °and R individually may be — O— , — S — , or — MR!— -, wherein R may be hydrogen, Cι_4 alkyl, 2-hydroxyethyl, 2-hydroxy-n-propyl, 2-acetoxyethyl, or 2-acetoxy-n-propyl; R-^' and R^nndividually may be hydrogen or a substituent selected from C 1 .4 alkyl; C j _4 alkoxy; C^ alkylthio; phenoxy or thiophenoxy optionally substituted by methyl, hydroxy, hydroxymethyl, thiol, carboxy, carboxymethyl, amino, methoxy, halogen, and/or nitro; or amino optionally mono- or disubstituted by C 1 .4 . alkyl or monosubstituted by cyano, nitro or phenyl optionally substituted by halogen, hydroxy, UBSTITUTE hydroxymethyl, thiol, carboxy, carboxymethyl, amino, and/or nitro; R -R » R Z nc * ^Z ■ Z ma ~- e hydrogen, a saturated or unsaturated substituent selected from C^.g alkyl, C j . halogenated alkyl, and cyclohexyl, or may be phenyl or benzyl, each optionally substituted by methyl, ethyl, hydroxy, hydroxymethyl, thiol, carboxy, carboxymethyl, amino, methoxy, nitro, cyano, trifluoromethyl, and/or halogen; R£-Rf , Rj, R Z ?R Z 2 R 13 Z and R 27 z -R 30 z may also be independently selected from C^. acyl, C j .g halogenated acyl, C _ monohydroxyacyl, and C2_ hydroxyalkyl; R Z and R Z may also be independently selected from C _Q hydroxyalkyl, Cμg alkoxy, Ci.g hydroxyalkoxy; and R^, Rχ, R^rand R^inay also independently be C2_ hydroxyalkyl; one of the substituents R^-R^ RfpRf R Z * n d R Z ma De un k eα* to either the atom in P χ that carries the chain containing Z- or to an atom in P χ adjacent thereto, to form a saturated, unsaturated, or aromatic, carbocyclic or heterocyclic 4-8 membered ring optionally containing 1-4 other identical or different hetero ring members selected from O, S, =N-, and NH, the ring being optionally substituted on its carbon and/or NH members by 1-8 identical or different substituents selected from halogen, hydroxy, methoxy, ethoxy, methyl, ethyl, cyano, azide, nitro, hydroxymethyl, 1-hydroxyethyl, 2-hydroxy-2-propyl, CF 3 , OCF 3 , SH, SCH3, SOCH3, SCF3, COOH, COOCH3, COCH3, CH=O, acetoxy, amino, mono- or dialkylamino totalling 1-4 carbon atoms inclusive, acetamido, N-methylacetamido, carboxamido, N-alkylated carboxamido containing 1-4 carbon atoms inclusive, hydroxyacetyl and hydroxyacetoxy; R£ may comprise G 1 as defined below; an optional ring may be formed between R 6 and P χ as described above for Rx- x 2 ; R Z , £ > R 7 Z . R 26 Z or R 27 Z may comprise an additional bond to P χ , thus completing an unsaturated linkage; and only one of the substituents R^-R^πmay be substituted or unsubstituted phenyl or benzyl. M and M' independently may be: SUBSTITUTE SHEET -o ■ N I R M wherein R-j^ and R may be the same or different and each may be hydrogen or a saturated or singly or multiply unsaturated, straight or branched, acyclic substituent containing 1-20 carbon atoms, not more than 16 halogen atoms, and not more than 6 heteroatoms selected from oxygen, nitrogen, and sulfur, in which the oxygen atoms total 4 or less, the nitrogen atoms total 4 or less, and the sulfur atoms total 2 or less, the heteroatoms being preferably situated in functional groups selected from hydroxy, amino, thiol, nitro, azide, ether, thioether, aldehyde, keto, carboxy, ester, amide, cyano, nitroguanidine, and cyanoguanidine; R may optionally comprise an additional bond to P χ group, thus completing an unsaturated linkage; Rfø or Rfø may optionally comprise the same or different values of G 1 , as defined below; Rfø or R may be linked to either the atom in P χ that carries the chain containing M and/or M' or to an atom in P χ adjacent thereto, to form a 4-8 membered ring defined as for the analogous R j -Rg -containing ring above. -Q"' independently may be: =0 =S ==N— FU Q o r =z=N — O— R Q P χ that carries the chain containing Q to form a 4-8 memebered ring defined above. T T RQ-RQ" are independently selected from: Q // I I ■ P- ■ P- I , I RQ R Q wherein Rr> and RQ may be the same or different and each may be selected from halogen and the values specified above for Rfø and Rfø; Rft and/or R7S may optionally comprise the same or different values of G as defined below; Q and Q * are as defined above; one of fr and R/ may be to the chain that carries R or to an atom in membered ring defined as for the analogous Rf-R^containing ring above. G and G^ independently comprise a group containing 1-3 fused or separate, sat¬ urated, unsaturated or aromatic 4-8 membered rings, each ring optionally containing 1-4 identical or different hetero ring members selected from X and =N-, each ring being optionally substituted on its carbon and/or NH members by 1-8 iden-tical or different substituents, preferably selected from halogen, hydroxy, methoxy, ethoxy, methyl, ethyl, cyano, azide, nitro, hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, 2- hydroxy-2-propyl, CF 3 , OCF3, SH, SCH3, SOCH3, SCF 3 , COOH, COOCH3, COCH3, CH=O, acetoxy, amino, mono- or dialkylamino totalling 1-4 carbon atoms inclusive, acetamido, N-methylacetamido, carboxamido, N-alkylated carboxamido containing 1-4 carbon atoms inclusive, hydroxyacetyl and hydroxyacetoxy; wherein for G- the optional second and third rings may be fused to the first ring and/or to one another or may be separate rings connected to one another and/or to the atom bearing G- by a single or double bond or by an intervening substituted or unsubstituted, linear or branched, saturated or unsaturated chain containing not more than 8 carbon atoms, not more than 8 halogens, and not more than 4 heteroatoms selected from oxygen, nitrogen, silicon, phosphorus and sulfur; and wherein for G* the first ring is singly or doubly bonded to P χ or to a component SUBST atom of the Sg chain connecting P χ and G^, and the optional second and third rings may be fused to the first ring or to one another or may be separate rings connected to one another and/or to the first ring by single or double bonds or by an intervening substituted or unsubstituted, linear or branched, saturated or unsaturated chain containing not more than 8 carbon atoms, not more than 8 halogens, and not more than 4 heteroatoms selected from oxygen, nitrogen, silicon, phosphorus and sulfur. The capping group E Q that terminates the connecting chain also may be selected from any of a surprisingly broad array of chemical groupings, and these chemical groupings can be composed of a far larger number of atoms than is found in the hydroxymethyl or 1-hydroxyethyl group. These chemical groupings may include, without limitation, hydrophobic entities such as alkyl, hydrogen, and halogenated alkyl, or may include, without limitation, quite hydrophilic moieties, such as hydroxy, thiol, carboxy and carboxy esters, amines, etc. It is well-known in the art that organic functional groups spanning a wide range of properties, from ionized and very hydrophilic to very hydrophobic, can be formed from multi-atom groupings of elements selected from carbon, hydrogen, halogen, oxygen, nitrogen, silicon, phosphorus, arsenic, boron and selenium. Indeed, for this invention the single restriction appears to be that S 0 E 0 taken together should not be hydroxymethyl or 1- hydroxyethyl bonded in the usual position in the parent compounds, since such compounds correspond to the skin-inflammatory and often tumor-promoting parent natural products. Thus, E Q may be a moiety E j , wherein E j is selected from =O, =S, =NH, =NORg wherein Rg is hydrogen or a C j -Cg normal or branched alkyl radical, =N-NH 2 , hydrogen, halogen, -OH, -SH, -NH 2 , ~NH-NH 2 , -N 3 , -CN, -NO, ~ NO 2 , --NHOH, -ONH 2 , or is selected from : T 2 T 2 „ s j T 5 T 5 - T 5" — T 1 -S--T 4 — S-T 4 I I I I o o SUBSTITUTE SHEET T 2' T 2' 1 ■ ■ 3 M 3 — T— P— T 3 — P— T 3 - {4 ' wherein T is selected from — O— , -S-, and -NH-; T-" is selected from =O, =S, and =N— R£, in which R£ may be hydrogen, hydroxy, cyano, or nitro; T^ is selected from =O and =S; T 3 , T*and T 4 are independently selected from -OH, -N^, -SH, -N3, -NH-NHg, and --NH--ORJ7, in which R£ may be hydrogen, C j _3 alkyl or C^. g acyl; T 3 may also be hydrogen or halogen; T -T 5 are independently selected from hydrogen and hydroxy; T 5 may also be halogen; R is selected from hydrogen, halogen, hydroxy, nitro, nitroso, cyano, azide, --NH . --NH--OH, -SH, --O--NH , ~ NH~NH , -T 1 -C(=T 2 )-T 3 , -C(=T 2 )~T 3 , -SiT 5 T 5 'τ 5 ", -T 1 -S(=O)(=T 2 )-T 4 , - S(=O)(=T 2 )-T 4 , -T 1 -P(-T 4 )-T 4 ', -P(-T 4 )-T 4, f -T1-P(=T 2 ')(-T 3 )-T 4 , and - P(=T 2 ')(~T 3 )-T 4 ; R| and R are individually selected from hydrogen, -C(=T 2 )- T , cyano, nitro, azide, halogen and a C j -C | 5 straight or branched chain, saturated, unsaturated and/or aromatic-containing alkyl moiety optionally containing not more than 10 halogen atoms and not more than 4 heteroatoms selected from oxygen, nitrogen and sulfur. Finally, if R£ is cyano or -C(=T 2 )~T 3 , then R or R may optionally be selected from ~SiT 5 T 5 'τ 5 ", ~T 1 -P(=T 2 ')(~T 3 )~T 4 , and -P(=T 2 ')(~T 3 )-T 4 ; and R£ and Rg are individually selected from hydrogen, halogen, cyano, nitro, - C(=T 2 )~T 3 , -T 1 ~C(=T )-T 3 , --CRJ;R R , ~SiT 5 T 5 T 5 ", -S(=O)(=T 2 )-T 4 , and ..P(=T 2 ')(-T 3 )-T 4 . In this invention, novel phorboids of the P j diterpene class may advantageously embody the general structure PJR, SUBSTITUTE SHEET wherein carbons (1 and 2) or (2 and 3) may be joined by a double bond; carbons (5 and 6) or (6 and 7) may be joined by a double bond; Si E j may be bonded to carbon 5, 6 or 7; R j ^i represents not more than 8 identical or different substituents bonded independently via single and/or double bonds to carbons 1, 2 and/or 3, which substituents may independently be halogen(s) and/or other groups, which halogens and groups taken together contain a total of not more than 30 carbon atoms, not more than 24 halogen atoms and not more than 9 heteroatoms selected from oxygen, nitrogen, silicon, phosphorus and sulfur; R^ represents not more than 6 identical or different substituents bonded independently via single and/or double bonds to carbons 5, 6 and/or 7, which substituents may independently be halogen(s) and/or other groups, which halogens and groups taken together contain not more than 12 carbon atoms, not more than 8 halogen atoms, and not more than 5 heteroatoms selected from oxygen, nitrogen, silicon, phosphorus and sulfur; and R^ represents not more than 10 identical or different substituents bonded independently via single or double bonds to carbons 9, 11, 12, 13 and/or 14, which substituents may independently be halogen(s) and/or other groups, the group or groups optionally completing 1-3 additional rings through bonds among themselves and/or 1-5 additional rings when taken together with A , A , a ring formed by A ~ and A^ together, and/or a bond to carbon atom 9, which halogen and groups taken together, include not more than 50 carbon atoms, not more than 24 halogen atoms, and not more than 15 heteroatoms selected from oxygen, nitrogen, silicon, phosphorus and sulfur. A preferred embodiment of P I R carries a substituted or unsubstituted cyclopropyl moiety, forming P j p wherein the R^ and R^ radicals may independently be hydrogen, halogen and/or other groups, which halogens and groups taken together contain a total of not more than 30 carbon atoms, not more than 24 halogen atoms and not more than 9 heteroatoms selected from oxygen, nitrogen, silicon, phosphorus and sulfur. In particularly preferred embodiments of P j p, carbon 2 carries a methyl group, J 1 is hydroxy, carbon 9 carries a hydroxy group in the alpha configuration, carbons 10 and 14 carry alpha hydrogens, carbon 11 carries a methyl group in the alpha configuration and R^ and R^ are both methyl, forming P j pp: In another preferred embodiment of PI R, an orthoester moiety is bonded to the 6- membered ring via one orthoester oxygen atom in the alpha configuration to carbon 9 and via two orthoester oxygen atoms in the alpha configuration to any two of carbons 12-14, forming Pi RR : SUBSTITUTE SHEET ( P 1IRPRD ) wherein ^ represents hydrogen, halogen or other group, the group optionally completing 1 additional ring to carbon 1, which group includes not more than 30 carbon atoms, not more than 16 halogen atoms, and not more than 9 heteroatoms selected from oxygen, nitrogen, silicon, phosphorus and sulfur. In a particularly preferred embodiment of P j RR, carbon 2 carries a methyl group, J is hydroxy, carbon 10 carries a hydrogen atom in the alpha configuration, carbon 11 carries a methyl group in the alpha configuration and carbon 13 carries an isopropenyl Novel phorboids of the P j diterpene class may also advantageously embody the general structure Pi j : wherein R ^ j represents not more than 8 identical or different substituents bonded independently via single and/or double bonds to carbons 1, 2 and/or 3, which substituents may independently be halogen(s) and/or other groups, which halogens and groups taken together contain a total of not more than 30 carbon atoms, not more than 24 halogen atoms and not more than 9 heteroatoms selected from oxygen, nitrogen, silicon, phosphorus and sulfur; R / jj represents not more than 6 identical or different substituents bonded independently via single and/or double bonds to carbons 5, 6 and/or 7, which substituents may independently be halogen(s) and/or other groups, which halogens and groups taken together contain not more than 12 carbon atoms, not more than 8 halogen atoms, and not more than 5 heteroatoms selected from oxygen, nitrogen, silicon, phosphorus and sulfur; carbon atom 9 may be unsubstituted or may carry a substituent defined as for RA2 above; and R^ represents not more than 10 identical or different substituents bonded independently via single or double bonds to carbons 9, 11, 12, 13 and/or 14, which substituents may independently be halogen(s) and/or other groups, the group or groups optionally completing 1-3 additional rings through bonds among themselves and/or 1-5 additional rings when taken together with A , A-", a ring formed by A- and A^ together, and/or a bond to carbon atom 9, which halogen and groups taken together, include not more than 50 carbon atoms, not more than 24 halogen atoms, and not more than 15 heteroatoms selected from oxygen, nitrogen, silicon, phosphorus and sulfur. In a preferred embodiment of P j j , carbons 13 and 14 of carry a substituted or unsubstituted cyclopropyl moiety, thus forming PJ N : SUBSTITUTE SHEET wherein the R^5I and R^6I radicals may independently be hydrogen, halogen and/or other groups, which halogens and groups taken together contain a total of not more than 30 carbon atoms, not more than 24 halogen atoms and not more than 9 heteroatoms selected from oxygen, nitrogen, silicon, phosphorus and sulfur. In especially preferred embodiments of Pi jj s j , carbon 2 carries a methyl group, J* is hydroxy, carbon.11 carries a methyl group in the alpha configuration, carbon 14 carries an alpha hydrogen and R^i and R^g j a e both methyl, forming PHNL' Among parent phorboids of the P2 class of indole/indene/benzofuran/benzothiophene derivatives, the novel compounds of this SUBSTITUTE invention may advantageously embody the general structure 2NN' wherein K β j represents 1-3 identical or different substituents located independently at carbons 5, 6, and/or 7, which substituents may independently be hydrogen, halogen and/or other groups which, taken together, contain not more than 40 carbon atoms, not more than 24 halogen atoms, and not more than 9 heteroatoms selected from oxygen, nitrogen, silicon, phosphorus, and sulfur, the groups being optionally connected to one another, to Kg and/or to Kg2 to form 1-3 additional carbocyclic or heterocyclic rings; and wherein K β 2 is hydrogen or a group which contains not more than 20 carbon atoms, not more than 24 halogen atoms, and not more than 6 heteroatoms selected from oxygen, nitrogen, silicon, phosphorus and sulfur, this group being optionally connected to B j or K to form an additional carbocyclic or heterocyclic ring. In a preferred embodiment of 2NN' ^1 anc * ^3 are hydr gen and K2 is -NH-, forming P 2NNN and K4 is hydrogen or other group containing not more than 20 carbon atoms, not more than 24 halogen atoms, and not more than 9 heteroatoms selected from oxygen, nitrogen, silicon, phosphorus and sulfur, the group being optionally connected to Kg to form an additional ring. Two particularly preferred embodiments of P2NNN com P r i se I*2L anc * ^2T' wherein P2L i s L ) wherein K β i» is hydrogen, halogen or other group which contains not more than 40 carbon atoms, not more than 24 halogen atoms, and not more than 9 heteroatoms selected from oxygen, nitrogen, silicon, phosphorus and sulfur, this group being optionally connected to K β 2 to form an additional ring; and wherein P2T is wherein a four-carbon saturated, unsaturated or aromatic ring connects positions 6 and 7 and substituents KJQ'^-13 mav independently be absent in favor of unsaturated linkages or may be hydrogen, halogen and/or other groups which, taken together, contain not more than 36 carbon atoms, not more than 24 halogen atoms, and not more than 9 heteroatoms selected from oxygen, nitrogen, silicon, phosphorus and sulfur. It will be appreciated that the many different permissible changes to the hydroxymethyl or 1-hydroxyethyl groups of the parent phorboids lead to diverse compounds with diverse biological properties, and different embodiments will be preferred for different utilities. If different protein kinase C isotypes and other proteins bearing phorboid-type binding sites have different biological functions, as has SUBSTITUTE SHEET been extensively hypothesized and to some extent demonstrated in biological experiments, then the novel comopunds of this invention with differing activity on different protein kinase C isotypes will obviously display a wide range of differing utilities. For example, a preferred set of compounds for anti-viral activity, including anti- retroviral and anti-Human Immunodeficiency Virus (HIV) activities, in human cells is generated by replacing the hydroxymethyl or 1-hydroxyethyl groups of parent phorboids with the following moieties: (i) dihalomethyl, trihalomethyl, — N3, -N^, -- CN, -COOH, -CH=CHCOOH, -CsCCOOH, -CSSH, -COSH, -SO 2 H, -SO3H, - P(=O)(R|)OH, ~P(=S)(R|)OH, -P(=O)(OR a )OH, -P(=S)(OR|)OH, ~CH=NOH, ~CH=NOCH 3 , ~CΗN(→O)CH 3 , -C(CH 3 )=NOH, -CH=CHR a , -CsC-R|, - CH 2 CsC-R a , -Si(CH3) OH, -Si(OH) 2 CH3, -SiCH 3 ) 2 F, -Si(CH 3 ) 2 Rl, - CH2Si(CH3)2R , or =CHR a , in which R is hydrogen or C j .12 linear or branched, saturated, unsaturated and/or aromatic hydrocarbon optionally substituted by not more than 16 halogens; or (ii) -CH2- or -CH(CH3)~, to either of which is bonded - R|, -N 3 , -NH2, -CN, -COOH, -COSH, -CSSH, -Si(CH3) 2 OH, ~Si(OH) CH 3 , - SiCH 3 ) 2 F, -SO 2 H, -SO3H, -PO3H2, -P(=O)(R|)OH, -P(=S)(R|)OH, - P(=O)(OR a )OH, -P(=S)(OR a )OH, the o-, m- or p-isomer of «M-C H 4 CH2"T3, the o-, m- or p-isomer of ~C 6 H 4 CH 2 -T3, -SR a , --SCH2CH2OH, -S(=O)~ CH 2 CH 2 OH, -S(CH 2 ) 3 OH, -S(CH 2 )4OH, -SCH2CH2SH, -M-C(=T 2 )-M'-R a except -OC=ONH 2 , --OCH 2 C(=O)CH3, -OCH 2 C(=NOH)CH 3 , the o-, m- or p- isomer of-M-C(=T2)-M , -C6H4-T3, or the Q , m- or p.-isomer of-M-C(=T 2 )-M'~ Preferred compounds for anti-viral use, for example, incorporate parent radicals selected from Pi pp, PIRRR. ^HN ' ^2L anc * ^2T' Dear i n g functionally diverse S χ E^ groups selected from (i) dihalomethyl, trihalomethyl, --N3, -NH2, -CN, -COOH, - CH=CHCOOH, -CsCCOOH, -CSSH, -COSH, -SO 2 H, -SO 3 H, -P(=O)(R a )OH, - P(=S)(R|)OH, -CH=NOH, -Si(CH 3 ) 2 OH, -Si(OH) 2 CH 3 , or (ii) -CH 2 - or - CH(CH 3 )~, to either of which is bonded ~R a , ~N 3 , -NH2, -CN, -COOH, -COSH, -CSSH, -Si(CH 3 ) OH, -Si(OH) 2 CH 3 , -SO 3 H, -PO 3 H 2 , ~P(=O)(R|)OH, the o-, m- or p-isomer of-M~C H CH2~T3, the o-, m- or p-isomer of ~C H4CH2-T3, ~SR a , -SCHgCHgOH, -S(=O)-CH2CH 2 OH, -S(CH 2 ) 3 OH, -S(CH 2 ) 4 OH, -SCH 2 CH 2 SH, the o-, m- or p-isomer of-M-C(-=T2)--M'-C6H4~T3, or the o^ m- or r-isomer of- in which R a is hydrogen or C l 2 linear or branched, saturated, unsaturated and/or aromatic hydrocarbon optionally substituted by not more than 16 halogens. The compounds of this invention have been found to possess valuable pharmacological properties. They block inflammation, block proliferation of cancer cells, and induce production of thrombolytic activity in human and veterinary medicine. These effects can be demonstrated, for example, by use of standard mouse ear inflammation tests by established agonists such as PMA and the ionophore A23187, by the inhibition of proliferation of human leukemic cells in culture via induction of differentiation, by assays of cytotoxicity against human cancer cells, by assays of inhibitory activity against acute and chronic HIV viral replication in human lymphocytes, and by measurement of fibrinolytic activity in cultured cells. These compounds also show selective effects as antagonists or protein kinase C in some cases, as noninflammatory agonists for protein kinase C in other cases, and as selective ligands for protein kinase C and/or for phorboid receptors. Thus, these compounds can be used as agents for the abrogation of pathophysiological conditions and disease states in applications such as anti- inflammatory, anti-psoriatic, anti-cancer, anti-ulcer, anti-hypertensive, anti-asthma, anti-arthritic, anti-autoimmune, anti-nociceptive, anti-secretory, anti-parasitic, anti- amoebic, anti-HIV replication, in prophylaxis against infection by any HIV form, and any other application in which pathological involvement of protein kinase C is found. The compounds of this invention can also be used in combination with other therapeutic agents, for example for use in the treatment of viral infections. Thus, a compound of this invention can be used in combination with a nucleoside analog such as azidothymidine or dideoxyinosine, a tetrahydroimidazo[4,5,l-jk][l,4]-benzodiazepin- 2(lH)-one derivative, other HIV reverse transcriptase inhibitors, HIV protease inhibitors, or HIV tat-gene function inhibitors for the prophylaxis against or treatment of HIV infections. A method for treating a mammal infected with a virus comprises administering to a mammal in need of such treatment an antivirally effective quantity of a composition comprising an acceptable pharmaceutical carrier and an antivirally active compound or compounds or a pharmaceutically acceptable salt thereof. Furthermore, the non-inflammatory agonists among the compounds of this invention may be used to achieve desired physiological results such as interferon release, interleukin induction, tumor necrosis factor production, immune system stimulation and/or reconstitution, insulin secretion, insulinomimetic activity, acceleration of wound healing, improvement in central nervous system functions such as memory and learning and abrogation of the symptoms or progress of Alzheimer's disease, and any other application for which desirable actions of protein kinase C are found. As phorboid receptor subtype- and/or protein kinase C substype-selective ligands, the compounds of this invention also have very valuable application as experimental agents for research into the role of protein kinase C and/or phorboid receptors in important biological processes and in human and veterinary diseases. Thus, their value extends to their use as pharmacological tools for in vitro and in vivo research, in a manner similar to the important roles that selection agonists and antagonists have SUBSTITUTE SH played in the studies of the mechanism of action of adrenergic, dopaminergic, opiate, benzodiaepine, cholinergic, and serotoninergic receptor systems, among others. In addition, the compounds can be used in in. vitro diagnostics (e.g., in an assay for 5 protein kinase C). They are also useful as intermediates in the production of other drugs, e.g., as described in the present invention. The compounds of this invention are generally administered to animals, including but not limited to fish, avians, and mammals including humans. The pharmacologically active compounds of this invention can be processed in 10 accordance with conventional methods of galenic pharmacy to produce medicinal agents for administration to patients, e.g., mammals including humans. The compounds of this invention can be employed in admixture with conventional excipients and carriers, i.e., pharmaceutically acceptable organic or inorganic carrier substances suitable for parenteral, enteral (e.g., oral) or topical application which do 15 not deleteriously react with the active compounds. Suitable pharmaceutically acceptable carriers include but are not limited to water, salt solutions, alcoholics, gum arabic, vegetable oils, benzyl alcohols, polyethylene glycols, gelatine, carbohydrates such as lactose, amylose or starch, magnesium stearate, talc, silicic acid, viscous paraffin, perfume oil, fatty acid esters, hydroxy methylcellulose, polyvinyl pyrrolidone, 20 etc. The pharmaceutical preparations can be sterilized and if desired mixed with auxiliary agents, e.g., lubricants, preservatives, stabilizers, wetting agents, emulsifiers, salts for influencing osmotic pressure, buffers, coloring, flavoring and/or aromatic substances and the like which do not deleteriously react with the active compounds. They can also be combined where desired with other active agents, e.g., enzyme 25 inhibitors, to reduce metabolic degradation. Such carriers do not include the following solvents when used alone: dimethylsulfoxide, acetone, or methanol or ethanol of greater than 80% concentration in water. For parenteral application, particularly suitable are injectable, sterile solutions, preferably oily or aqueous solutions, as well as suspensions, emulsions, or implants, 30 including suppositories. Ampoules are convenient unit dosages. For enteral application, particularly suitable are tablets, dragees, liquids, drops, suppositories, or capsules. A syrup, elixir, or the like can be used wherein a sweetened vehicle is employed. A preferred method of administration comprises oral dosing, with tablets, dragees, 35 liquids, drops, or capsules. For the oral route of administration, either compounds of this invention lacking functional groups destroyed by acid, or tablets or capsules which protect the active compound from upper gastrointestinal acidity, are preferred. Sustained or directed release compositions can be formulated, e.g., in liposomes or in compositions wherein the active compound is protected with differentially 40 degradable coatings, e.g., by microencapsulation, multiple coatings, absorption onto charcoal, entrapment in human serum albumin microspheres, etc. It is also possible to freeze-dry the new compounds and use the lyophilizates obtained, for example, for the preparation of products for injection. Another preferred route of administration comprises topical application, for which are employed nonsprayable forms, viscuous to semi-solid or solid forms comprising a carrier compatible with topical application and having a dynamic viscosity compatible with topical application, preferably greater than water. Suitable formulations include but are not limited to solutions, suspensions, emulsions, creams, ointments, powders, liniments,salves, aerosols, etc., which are, if desired, sterilized or mixed with auxiliary agents, e.g., preservatives, stabilizers, wetting agents, buffers or salts for influencing osmotic pressure, etc. For topical application, also suitable are sprayable aerosol preparations wherein the active ingredient, preferably in combination with a solid or liquid inert carrier material, is packaged in a squeeze bottle or in admixture with a pressurizied volatile, normally gaseous propellant, e.g., a freon. The compounds of this invention, admixed with appropriate carriers, may also be delivered to subjects by means of an externally connected or internally implanted pumping device to give a controlled and/or sustained release of the therapeutic mixture, or by means of a patch of natural or synthetic fabric and/or polymer impregnated with the compounds in a suitable carrier and affixed to the skin to achieve transdermal release and absorption of the active compounds. The compounds of this invention may also be modified by covalent attachment of metabolically modifiable groups, to form "prodrugs" which are released by cleavage in vivo of the metabolically removable groups. For example, amine, hydroxy and/or thiol groups present in many compounds of this invention may be converted to prodrugs by covalent attachment of acyl or aminoacyl moieties. Likewise, compounds of this invention containing carboxylic, sulfonic, phosphoric, phosphonic or related free acids, including those in which one or more oxygen atoms are replaced by sulfur, may be converted to prodrugs by formation of their esters or amides by covalent attachment of alcohols, amines, amino acids and the like. Compounds of this invention may also incorporate N-alkyldihydropyridine moieties, which become localized to the central nervous system after administration to the subject and subsequent metabolic modification of the N-alkyldihydropyridine group in the central nervous system. It wilkbe recognized by persons with ordinary skill in medicinal chemistry that conversion of alcohol-, amine-, thiol- or acid-containing compounds of this invention to prodrugs is preferably done by derivatization of such groups located in regions of the molecule having minimal steric hindrance, to permit access of metabolizing enzymes, other bioreactants or water. Such alcohol-, amine-, thiol- or acid-containing groups may be located in any of the parent, side-chain or capping-group moieties described above. A prodrug-type group such as the N-alkyldihydropyridine group, however, is preferably added to the parent moieties P j -Pg, etc., unless it is found for a given compound that the N-alkyldihydropyridine group and /or its metabolic pyridinium oxidation product has desirable bioactivity when located in the side chain or capping group of a compound of this invention. Generally, the compounds of this invention are dispensed in unit dosage form comprising 0.01 to 1000 mg in a pharmaceutically acceptable carrier per unit dosage. They are incorporated in topical formulations in concentrations of about 0.01 to 10 weight percent. It will be appreciated that the actual preferred amounts of active compound in a specific case will vary according to the specific compound being utilized, the particular compositions formulated, the mode of application, and the particular situs and organism being treated. Dosages for a given host can be determined using conventional considerations, e.g., by customary comparison of the differential activities of the subject compounds and of a known agent, e.g., by means of an appropriate, conventional pharmcological protocol. It will be appreciated that such starting materials from natural sources or from total or partial synthesis may be altered in very diverse ways, consistent with this invention, to obtain compounds with novel primary biological/medicinal activities resulting from, and controlled by, the specific new S 0 E 0 or S χ El group created; such properties include for example loss of skin inflammatory activity and appearance or retention of anti-inflammatory, anti-HIV, anti-leukemic and cytokine-induction activities. It is also possible to introduce an extremely wide variety of changes into either (i) the groups replacing the hydroxymethyl/l-hydroxyethyl group or (ii) the previously-described parent phorboid structures, to obtain new entities with improved secondary properties, such as, variously, hydrophobicity, water solubility, potency, oral availability, metabolic and chemical stability, reduced therapeutic side effects, and so on, using strategies and techniques widely recognized in the art of medicinal chemistry and pharmacology. Starting materials for the synthesis of the compounds of this invention may be obtained from any of a wide variety of natural sources, and the diterpene, indole alkaloid, diacylglycerol, diaminobenzyl alcohol and polyacetate compounds are available by total synthesis. Methods for generating phorboids modified in the parent portion and for obtaining hydroxymethyl/1-hydroxyethyl-modified phorboids»are discussed below, separately for each phorboid parent class. Compounds of this invention from the diterpenoid (P j ) class of phorboids may be obtained by semisynthetic procedures, starting from any of a variety of compounds from naturally occurring sources as described in the literature [see Naturally Occurring Phorbol Esters, ed. F.J. Evans, CRC Press, Boca Raton (1986), chapters 7, 8 and 9 and references cited therein]. Furthermore, these diterpene phorboids are available by total synthesis from common organic chemical starting materials. These syntheses provide a variety of approaches and associated flexibility in arriving at diverse functionalities on the parent nucleus and on the final S Q E 0 or S χ E χ side chain [see Paquette, L. et al., J. Am. Chem. Soc. 106, 1446-1454 (1984); Rigby, J. and Moore, T., J. Org. Chem. 55. 2959-2962 (1990); Wender, P. et al.. J. Am. Chem. Soc. 111. 8954-8957 (1989); Wender, P. et aL J, Am. Chem. Soc. Ill, 8957-8958 (1989); and Wender, P. and McDonald, F..J. Am. Chem. Soc. 112. 4956-4958 (1990)]. The means for modifying the hydroxymethyl group of diterpenoid phorboids to produce the compounds of this invention will be obvious to workers with ordinary skill in synthetic organic chemistry. Methods particularly suited to introduction of silicon- and phosphorus-containing functions are described below. In many diterpenoid phorboids the hydroxymethyl group may be modified without the necessity of protecting other functional groups in the molecule. In other cases, especially when strong nucleophiles or bases are used, other regions of the molecule must be suitably protected using methodologies widely practiced in synthetic organic chemistry. Frequently one or more oxygen atoms must be blocked before some types of chemical modifications may be accomplished on the hydroxymethyl group or on other portions of the diterpene parent. Some, but not the only, useful protecting groups for the oxygen atoms present as hydroxy groups are acyl, benzyl, trialkylsilane, benzyloxycarbonyl, 4'methoxyphenyldiphenylmethyl and trimethylsilylyethoxycarbonyl, which are variously stable to or removed under acidic, basic or reducing conditions or with fluoride ion reagents. Carbonyl functions may be protected by conversion to acetals or ketals, or by reduction to the alcohol level followed by protection with standard protecting groups for the hydroxy group. With or without such protection of non-hydroxymethyl portions of the parent diterpene the hydroxymethyl may, for example, be conveniently capped under very mild conditions by treatment with a substituted or unsubstituted alkyl, aryl, or aralkyl isocyanate, optionally containing silicon or phosphorus atoms in a variety of functional groups, in the presence of a catalyst such as dibutyltin dilaurate. The resulting compounds lack the toxic inflammatory activity of the phorboid from which they were derived, and have themselves anti-inflammatory utility. Illustrations are provided in the Examples below. Conversion of the hydroxy group to a halogen or pseudohalogen not only in itself provides active and useful compounds, but also permits the displacement of the resultant electrophile from the protected or in some cases, unprotected, parent nucleus by a very wide range of nucleophiles. Persons with ordinary skill in the art of organic synthesis will recognize that such nucleophiles may include, without limitation, reagents having carbon, hydrogen, oxygen, nitrogen, sulfur, phosphorus, silicon, arsenic, born, and/or selenium atoms in their structures. Particular examples would be reaction with ammonia, methylamine, the sodium salt of dimethylphosphine, trimethylphosphite, triphenylphosphine, potassium sulfite, trimethylsilylmethyl-metal salts, lithium trimethylsilylacetylide, sodium cyanide, N-methyl-2-hydroxyethyl amine, l[H]-tetrazole, or with the sodium salt of 2-mercaptoethanol, 3-mercaptoethanol, or of hydroxymethylphenol. Many variations may be executed, as described for nucleophilic displacement of electrophilic groups in organic molecules by standard textbooks of synthetic organic chemistry, such as J. March, Advanced Organic Chemistry. Third Edition, Wiley-Interscience, New York, 1985. As an illustration, 20- deoxy-20-chlorophorbol 12, 13-bis-diphenylphosphate yields 20-deoxy-20- (pentadecafluoro-[lH,lH]-octylthio)phorbol 12-butyrate 13-diphenylphosphate upon treatment with sodiopentadecafluoro-[lH,lH]-octylthiol. As another example, the 20- phosphonic acid derivative of 20-deoxy-resiniferonol 9,13,14-orthophenylacetate may be made by reacting the sodium salt of dibenzylphosphonate with 20-deoxy-20- bromoresiniferonol 9,13,14-orthophenylacetate to form 20-deoxy-20- dibenzylphosphonyl resiniferonol 9,13,14-orthophenylacetate dibenzylphosphonyl followed by catalytic hydrogenolysis of the benzyl ester groups to yield the free phosphonic acid derivative. By use of protecting groups or modifications of the diterpenoid parent using methods well-known in the art of synthetic chemistry, the hydroxy group of the hydroxymethyl moiety may be replaced by a metal and then reacted with an electrophile, effectively replacing the hydroxy with a group derived from the electrophile. The techniques for this replacement are obvious to workers with ordinary skill in organic synthesis, in that replacement of the hydroxymethyl hydroxy group by halogen in a suitably protected or modified diterpene permits strong and/or hard nucleophiles to be generated by the use of metals or strong bases, and persons with ordinary skill in the art of organic chemistry will recognize that such nucleophiles can be contacted with a very diverse range of electrophilic reagents having carbon, hydrogen, oxygen, nitrogen, sulfur, phosphorus, silicon, arsenic, boron and/or selenium atoms in their structures to obtain hydroxymethyl-modified diterpenes of widely varying structures. As one approach among many, the hydroxymethyl group of an appropriately protected diterpene may be converted to the 20-bromo derivative with methanesulfonyl bromide in dimethylformamide/pyridine. The resulting bromide may be modified by halogen-metal exchange using appropriately active metals or metal-containing reagents such as magnesium, zinc, alkali metals, metal alkyl reagents and so on, to obtain carbanionic character at the carbon atom previously bearing the hydroxy group, as shown in the following structures, which also illustrate typical protection of oxygen functions elsewhere in the molecule: SUBSTITUTE SHEET wherein Met isithe metal ion, PGi -PG 3 are typically selected from the list above and PG4 is typically 2',2'-propylidene or dialkyl- or diarylsilyl. PG3 may be unnecessary in 25 some cases (i.e. may be hydrogen or an anionic charge). The simultaneous presence or subsequent addition to the metal/anion-containing reaction of an electrophile such as, without limitation, an aldehyde, ketone, epoxide or oxetane then provides, after reacton and workup, compounds having one or more methylenes inserted between the original hydroxy group and the methylene to which it was attached. This methodology 30 is particularly advantageous for replacement of the hydroxy with a group containing silicon, phosphorous or other atoms by contacting the anionic metal derivative of the parent nucleus with electrophilic reagents having halogen or pseudohalogen groups, in addition to other functions chosen for biological specificity, bonded directly to the silicon orφhosphorus atoms, affording compounds with useful biological activity. 35 For those diterpene-type phorboids wherein the hydroxy of the hydroxymethyl group is allylic, such as phorbol, ingenol, and resiniferonol esters, the replacement of the hydroxy by chloro or preferably by bromo or iodo yields compounds that can be conveniently reacted with activated zinc in the presence of electrophiles such as, without limitation, aldehydes, ketones, epoxides, or oxetane; the resultant compounds 40 have one or more methylenes inserted between the original hydroxy group and the methylene to which it was attached, or, after an allylic rearrangement, a new functional group results at position 7 of the diterpene skeleton. An illustration of this would be the reaction of 20-deoxy-20-chlorophorbol 12-myristate 13-acetate with an excess of formaldehyde and an excess of zinc in the presence of tetrahydrofuran and saturated ammonium chloride solution with vigorous stirring for 24 hours. The resultant compound has the 6,7-double bond rearranged to the 6,20-position and bears a new hydroxymethyl group attached to position 7 instead of to position six as in the parent diterpene, and this compound, 12-beta-myristoyloxy 13-acetoxy-4,9-dihydroxy-7- hydroxymethyl- l,6(20)-tigliadien-3-one, has good anti-inflammatory activity. Alternatively, the hydroxy group on the hydroxymethyl of appropriately protected or modified diterpenoids may be oxidized to an aldehyde and then reacted via condensation or addition chemistries to provide a very wide variety of modified indolactams. Examples, without limitation, would be reactions with Wittig reagents; hydroxylamines; hydrazines; semicarbazides; ammonia, primary amines or secondary amines followed by sodium cyanoborohydride reduction to primary amines, secondary amines or tertiary amines, respectively; or Grignard reagents. Many variations may be executed as described in standard textbooks of synthetic organic chemistry, such as J. March, op cit. After completion of reactions in the hydroxymethyl region, an acetonide group protecting the 3-OH and 4-OH groups is removed with mild acid followed by reoxidation of the 3-OH to keto with sulfur trioxide-pyridine- dimethylsulfoxide. Trialkylsilane protecting groups PG^ and PG2 may then be removed with fluoride ion, preferably followed by derivatization of the now-free 12- and 13-OH's with acylating agents, isocyanates, alkyl- or aryl chloroformates or alkylating agents to establish hydrophobic groups in this region of the diterpene. Even a relatively base-sensitive compound such as a phorbol 12,13-diester may be oxidized to the 20-aldehyde with manganese dioxide and reacted directly with stabilized Wittig reagents such as methyl triphenylphosphoranylideneacetate, to yield a 20-deoxy-20-methoxycarbonylmethylidenephorbol 12,13-diester. Alternatively, a phorbol 12,13-diester may be selectively protected at the 4 and 9 hydroxy groups using trimethylsilyl trifluoromethanesulfonate, followed by reaction with manganese dioxide to obtain a protected aldehyde. The latter compound may be successfully treated with strong Wittig reagents such as the lithium salt of 2- hydroxyefchylidenetriphenylphosphorane, followed by deprotection with tetrabutylammonium fluoride to obtain the corresponding chain-extended, 20,21- didehydro-21,22-dihomophorbol diester. The hydroxymethyl group of suitable diterpene phorboids may be oxidized to the carboxylic acid level by methods well-known in the art or these carboxylic acids may be prepared by modifications of the total syntheses described in the literature cited above. Besides being useful examples of this invention themselves these acids permit the preparation of further modified diterpene phorboids. For example, this carboxylic group may be activated for condensation reactions by any of a number of well-known methods, e.g. by conversion to an acyl halide or to an active ester such as the N- succinimidyl ester. The resultant activated carboxyl may then be easily converted to simple or multifunctional ester, amide, or thioester derivatives by reaction with alcohols, amines, or thiols respectively, alone or in the presence of condensation catalysts. The use of the methods of total synthesis as described in the literature cited above permits specific modifications of the parent structures of the diterpenoids. By established techniques in the art of organic synthesis modified parent structures may be obtained which embody alterations at the hydroxymethyl group as well, and which have useful biological activity. This wide variety of modified diterpenoid structures may result from the use of modified starting materials, from modifications of one or more synthetic steps or from a combination of both. Starting materials for the synthesis of the compounds of this invention from the indolactam (P2) class of phorboids may be obtained from any of a variety of natural sources as described in the literature [T. Sugimura, Gann, 73 499-507 (1982), H. Fujiki and T. Sugimura, Advances in Cancer Research. 49. 223-264 (1987), K. Irie and K. Koshimizu, Mem. Coll. Agric. Kyoto Univ.. 132. 1-59 (1988) and references cited therein]. Furthermore, these indolactam phorboids are available by total synthesis from common organic chemical starting materials. These syntheses provide a considerable variety of approaches and associated flexibility in arriving at highly diverse functionalities on the parent nucleus and on the final S 0 E 0 or S χ E χ side chain, and include, but are not limited to, the procedures described by Y. Endo et al.. Tetrahedron. 42, 5905-5924 (1986), S. de Laszlo et ah, J. Chem. Soc. Chem. Comm.. 344-346 (1986), S. Nakatsuka et al.. Tetrahedron Letters. 27, 5735-5738 (1986) and Tetrahedron Letters. 28, 3671-3674 (1987), H. Muratake and M. Natsume, Tetrahedron Letters. 28, 2265-2268 (1987), M. Mascal and C. Moody. T. Chem. Soc. Chem. Comm.. 589-590 ( 1988); A. Kozikowski et ah, J. Am. Chem. Soc. 111. 6228-6234 (1989), and T. Kogan et aL, Tetrahedron. 46, 6623-6632 (1990) and references therein. Given indolactams containing hydroxymethyl groups, the means for modifying the hydroxymethyl group to produce the compounds of this invention will be obvious to workers with ordinary skill in synthetic organic chemistry. Methods particularly suited to introduction of silicon- and phosphorus-containing functions are described below. In some cases, the hydroxymethyl group may be modified once other regions of the molecule have been suitably protected using methodologies widely practiced in synthetic organic chemistry. In some specific cases the indole nitrogen must be blocked before some types of chemical modifications may be accomplished on the hydroxymethyl group or on other portions of the indolactam parent. Some, but not the only, useful protecting groups for the indole nitrogen are t-butoxycarbonyl, acetyl, benzyl, trimethylsilylyethoxymethylene, benzyloxycarbonyl and benzenesulfonyl, which are variously stable to or removed under acidic, basic or reducing conditions or 5 with fluoride ion reagents. With or without such protection the hydroxymethyl may, for example, be conveniently capped under very mild conditions by the treatment with a substituted or unsubstituted alkyl, aryl, or aralkyl isocyanate, optionally containing silicon or phosphorus atoms in a variety of functional groups, in the presence of a catalyst such as dibutyltin dilaurate. The resulting compounds lack the toxic 10 inflammatory activity of the phorboid from which they were derived, and have themselves anti-inflammatory utility. As an illustration, treatment of (-)-l-[2'- (triphenyloctylindolactam V with methylisocyanate in the presence of dibutyltin dilaurate and 4-dimethylaminopyridine in tetrahydrofuran affords 14-O-(N- methyl)carbamoyl-7-octyl-(9S, 12S)-indolactam V. 15 Conversion of the hydroxy group to a halogen or pseudohalogen not only in itself provides active and useful compounds, but also permits the displacement of the resultant electrophile from the protected or in some cases, unprotected, parent nucleus by a very wide range of nucleophiles. Persons with ordinary skill in the art of organic synthesis will recognize that such nucleophiles may include, without limitation, 20 reagents having carbon, hydrogen, oxygen, nitrogen, sulfur, phosphorus, silicon, arsenic, born, and/or selenium atoms in their structures. Particular examples would be reaction with ammonia, methylamine, the sodium salt of dimethylphosphine, trimethylphosphite, triphenylphosphine, potassium sulfite, trimethylsilylmethyl-metal salts, lithium trimethylsilylacetylide, sodium cyanide, N-methyl-2-hydroxyethyl amine, 25 l[H]-tetrazole, or with the sodium salt of 2-mercaptoethanol, 3-mercaptoethanol, or of hydroxymethylphenol. Many variations may be executed, as described in standard textbooks of synthetic organic chemistry, such as J. March, Advanced Organic Chemistry. Third Edition, Wiley-Interscience, New York, 1985. As an illustration, 14- O-methanesulfonyl-1-trimethylsilylmethylindolactam V yields 14-deoxy-14- 30 (pentadecafluoro-[lH,lH]-octylthio)-l-trimethylsilylmethylindolactam V upon treatment with sodiopentadecafluoro-[lH,lH]-octylthiol. In a similar manner 14- deoxy- 14-(pentadecafluoro-[ 1 H, 1 H]-octylthio)-6,7-tetramethyleneindolactam V is prepared. See Y. Endo et al.. Tetrahedron. 42. 5905-5924 (1986) for a synthesis of 6,7- tetramethyleneindolactam V. As a further illustration, treatment of 14-O- 35 methanesulfonyl-7-[2'-(2"-diphenylphosphonylethyl)aminoethyl]-indolactam V with the sodium salt of 4-t-butyldimethylsilyloxy-2-phenylphenol followed by treatment of the product with tetrabutylammonium fluoride in tetrahydrofuran affords 14-O-(4'- hydroxy-2'-phenyl)phenyl-7-[2'-(2"-diphenylphosphonylethyl)aminoethyl]-indolactam V. In a similar manner 14-O-(5'-hydroxy- -naphthyl)-7-[ ,l'-dimethyl-3'- 40 (hexyldimethylsilyl)propyl]-octylindolactam V, 14-O-(3'-hydroxy-5'-benzyloxy)phenyl- 7-octylindolactam V, 14-O-(4'-hydroxy-2'-phenyl)phenyI-6,7-tetramethyleneindolactam V, 14-O-(5'-hydroxy- -naphthyl)-6,7-tetramethyleneindolactam V, 14-O-(3'-hydroxy- 5'-benzyloxy)phenyl-6,7-tetramethyleneindolactam V are prepared. As a further illustration, treatment of 14-O-methanesulfonyl-7-octylindolactam V with sodium sulfite in methanol provides 14-deoxy-7-octylindolactam V 14-sulfonic acid. In a similar manner 14-deoxy-6,7-tetramethyleneindolactam V 14-sulfonic acid is prepared. As another example, the 14-phosphonic acid derivative of 14-deoxy-6,7- tetramethyleneindolactam V may be made by reacting the sodium salt of dibenzylphosphonate with 14-O-methanesulfonyl-7-octylindolactam V to form 14- deoxy-14-dibenzylphosphonyl-6,7-tetramethyleneindolactam V followed by catalytic hydrogenolysis of the benzyl ester groups to yield the free phosphonic acid. By use of protecting groups or modifications of the indolactam parent by methods well-known in the art of synthetic chemistry, the hydroxy group of the hydroxymethyl moiety may be replaced by a metal and then reacted with an electrophile, effectively replacing the hydroxy with a group derived from the electrophile. The techniques for this replacement are obvious to workers with ordinary skill in organic synthesis, in that replacement of the hydroxymethyl hydroxy group by halogen in a suitably protected or modified indolactam permits strong and/or hard nucleophiles to be generated by the use of metals or strong bases, and persons with ordinary skill in the art of organic chemistry will recognize that such nucleophiles can be contacted with a very diverse range of electrophilic reagents having carbon, hydrogen, oxygen, nitrogen, sulfur, phosphorus, silicon, arsenic, boron and/or selenium atoms in their structures to obtain hydroxymethyl-modified indolactams of widely varying structures. As one approach among many, the 14-O-methanesulfonyl derivative of an appropriate indolactam may be converted to an iodo compound with sodium iodide in acetone. The resulting iodide may be modified by halogen-metal exchange using appropriately active metals or metal-containing reagents such as magnesium, zinc, alkali metals, metal alkyl reagents and so on, to obtain carbanionic character at the carbon atom previously bearing the hydroxy group, as UBSTITUTE SHEET wherein Met is the metal ion, PG5 may be one of the indole nitrogen protecting groups listed above, and PGg may be unnecessary (i.e. may be hydrogen or an anionic charge), may be benzyl (removable by hydrogenolysis) or may be a stable group, such as methyl or ethyl, intended to remain in the final bioactive synthetic product. The simultaneous presence or subsequent addition to the reaction of an electrophile such as, without limitation, an aldehyde, ketone, epoxide or oxetane then provides, after reacton and workup, compounds having one or more methylenes inserted between the original hydroxy group and the methylene to which it was attached. This methodology is particularly advantageous for replacement of the hydroxy with a group containing silicon, phosphorous or other atoms by contacting the anionic metal derivative of the parent nucleus with electrophilic reagents having halogen or pseudohalogen groups, in addition to other functions chosen for biological specificity, bonded directly to the silicon or phosphorus atoms, affording compounds with useful biological activity. Alternatively, the hydroxy group on the hydroxymethyl of appropriately protected or modified indolactams may be oxidized to an aldehyde and then reacted via condensation or addition chemistries to provide a very wide variety of modified indolactams. Examples, without limitation, would be reactions with Wittig reagents, hydroxylamines, or Grignard reagents. Many variations may be executed as described in standard textbooks of synthetic organic chemistry, such as J. March, op cit. As an illustration, the aldehyde, 14-deoxy-14-oxo-7-octylindolactam V, may be prepared by oxidation of the parent hydroxymethyl compound with periodinane among other oxidizing agents. This aldehyde may be treated with O-(4- mercaptophenyl)hydroxylamine hydrochloride in ethanol to afford the O-(4- mercaptophenyl)oxime. This aldehyde may also be treated with N -(3- methoxyphenyl)semicarbazide to afford the corresponding N -(3- methoxyphenyl)semicarbazone. The O-(4-mercaptophenyl)hydroxylamine hydrochloride may be prepared from O-(4-nitrophenyl)hydroxylamine hydrochloride [A. Hirsch et aL, J- ed. Chem.. 20, 1546-1551 (1977)] in ways obvious to one with ordinary skill in the art of organic synthesis. These aldehydes may also be obtained by reduction of appropriate carboxylic acid derivatives by application of well-known techniques. As an illustration, 9- deshydroxymethyl-9-carbomethoxy-6,7-tetramethyleneindolactam V (prepared as described elow) may be reduced to the aldehyde, 14-deoxy-14-oxo-6,7- tetramethyleneindolactam V, by any of several reagents, for example diisobutylaluminum hydride. This aldehyde may be further modified to afford the O- (4-mercaptophenyl)oxime and the N -(3-methoxyphenyl)semicarbazone in the manner described above. The hydroxymethyl group of suitable indolactam phorboids may be oxidized to the carboxylic acid level by methods well-known in the art or these carboxylic acids may be prepared by modifications of the total syntheses described in the literature cited above. Besides being useful examples of this invention themselves these acids permit the preparation of further modified indolactams. For example, this carboxylic group may be activated for condensation reactions by any of a number of well-known methods, e.g. by conversion to an acyl halide or to an active ester such as the N- succinimidyl ester. The resultant activated carboxyl may then be easily converted to simple or multifunctional ester, amide, or thioester derivatives by reaction with alcohols, amines, or thiols respectively, alone or in the presence of condensation catalysts. As an illustration, rac-9-deshydroxymethyl-9-carboxyindolactam V (obtained as described below) may be treated with N-hydroxysuccinimide and dicyclohexylcarbodiimide in acetonitrile. After purification, the resulting N- succinimidyl ester may be treated with 3-amino-l,2-propandiol and 4- dimethylaminopyridine in methylene chloride/tetrahydrofuran to afford rac-9- deshydroxymethyl-9-[N-(2',3'-dihydroxy)propyl]carboxamidoindolactam V. The stereoisomers may be obtained separately either by using optically active starting materials or by separation from the mixture by chromatography on an enantioselective column packing [D. Armstrong, Analytical Chem.. 59. 84-91 A (1987)]. The total syntheses described in the literature cited above are also amenable to extensive adaptations so as to provide a wide variety of modifications in the parent structures of the indolactam group. By established techniques in the art of organic synthesis modified parent structures may be obtained which embody alterations at the hydroxymethyl group and which have useful biological activity. This extremely wide variety of modified indolactam structures may result from the use of modified starting materials, from modifications of one or more synthetic steps or from a combination of both. As an illustration, 9-deshydroxymethyl-9-carboxy-6,7-tetramethyleneindolactam V may be prepared from 4-nitro-6,7-tetramethylenegramine (Y. Endo et aL, op cit.) by the application of several routes obvious to workers with ordinary skill in organic synthesis. For example, methyl α-nitro-4-amino-6,7-tetramethyleneindole-3 acetate is prepared from 4-nitro-6,7-tetramethylenegramine in the manner described by T. Masuda et al.. Agric Biol. Chem.. 53, 2257-2260 (1989). Alkylation of the amino group of this compound with benzyl D-α-trifluoromethylsulfonyloxyisovalerate in the manner described by T. Kogan et aL, op cit.. affords an optically active intermediate which, after removal of the benzyl ester and reduction of the nitro group, is lactamized in the manner of T. Masuda et aL, op cit.. and methylated by treatment with formaldehyde/sodium cyanoborohydride to afford 9-deshydroxymethyl-9- carbomethoxy-6,7-tetramethylene-9S,12S-indolactam V. Hydrolysis with methanolic sodium hydroxide affords 9-deshydroxymethyl-9-carboxy-6,7-tetramethylene-9S,12S- indolactam V. To further illustrate the synthesis of the compounds of this invention, the modified indolactam, 1 ,2,4,5,6,8-hexahydro-5-methyl-2-( 1 -methylethyl)-3H— pyrrolo(4,3,2-gh)-l,4-benzodiazonin-3-one, may be prepared from N-BOC-4- nitrotryptophanol [Y. Endo et al.. Tetrahedron. 42. 5905-5924 (1986)] by the 5 application of several routes obvious to workers with ordinary skill in synthetic chemistry. For example, preparation of N-BOC-4-nitrodeoxytryptophanol may be accomplished by reduction of the phenylselenium derivative with triphenyltinhydride [D. Clive et al^ Chemical Communications. 41-42 (1978)] or by reduction of the mesylate derivative with lithium triethylborohydride [R.W. Holder and M.G. Matturro, 10 J. Org. Chem.. 42. 2166- 168 ( 1977)] or by several other routes. From the deoxy derivative the synthesis could proceed in the manner described by Y. Endo et al^ loc cit., for the hydroxy derivative. Specifically, the resulting substituted indolylvaline methyl ester is hydrolysed and the resulting acid is converted to the N-succimidyl ester. Upon cleavage of the BOC group under acidic conditions cyclization to the lactam 15 occurs directly to provide all four stereoisomers, i.e., 2R,5R-, 2R.5S-, 2S.5S-, and 2S,5R- l,2,4,5,6,8-hexahydro-5-methyl-2-(l-methylethyl)-3H-pyrrolo (4,3,2-gh)-l,4- benzodiazonin-3-one. These stereo-isomers may be obtained separately either by beginning the synthesis with optically active N-BOC-4-nitrotrytophanol or by separation from the mixture by chromatography on an enantioselective column 20 packing [D. Armstrong, Analytical Chem.. 59. 84-91A (1987)]. Similarly, the further modified indolactam, l-(l-oxobutyl)-l,2,4,5,6,8-hexahydro-5-methyl-3H-pyrrolo(4,3,2- gh)-l,4-benzodiazonin-3-one, may be prepared. Specifically, hydrogenation of N-BOC- 4-nitrodeoxytrytophanol over palladium on carbon will provide N(2')-BOC-4- aminodeoxytrytophanol. Alkylation of this compound with methyl bromoacetate 25 affords N-[3-(N-BOC-2-aminopropyl)-4-indolyl]-glycine methyl ester [Y. Endo, et al.. Chem. Pharm. Bull. 30. 3457-3460 (1982)]. Acylation of this material with butanoyl chloride in the presence of potassium carbonate or pyridine will provide N-butanoyl- N-[3-(N-BOC-2-aminopropyl)-4-indoIyl]glycine methyl ester. This latter material may be converted to l-(l-oxobutyl)-l,2,4,5,6,8-hexahydro-5-methyl-3H-pyrrolo(4,3,2-gh)- 30 l,4-benzodiazonin-3-one by application of the methods of Y. Endo, et al^ loc cit. (1986). The enantiomers, 5R- and 5S-, may be obtained separately by beginning with optically active materials as described above or by separation at the final stage by chromatography also as described above. Beyond the extensive changes in the hydroxymethyl group of indolactam and 35 related P2~type parent phorboids described above, the present invention also discloses broad and diverse alterations which are accomodated in the non-hydroxymethyl regions of the parent P2*type phorboids. Such modifications of the indolactam parents can be carried out before, after or in alternating fashion with respect to construction of the hydroxymethyl modifications, depending on obvious considerations of chemical 40 stability of the various functional groups in intermediates being subjected to chemical modifications. It is obvious to one skilled in the art that many modified indolactam parents may be obtained by carrying a modification through the de novo synthsis as described in the literature cited above. As an illustration, 7-alkylindolactam Vs containing a wide variety of alkyl groups may be prepared by application of the method of A. Kozikowski et al., op cit.. to a variety of alkyl substituted isoxazolines. As a further illustration, the modified indolactam, l-( -octyl)-l,2,4,5,6,8-hexahydro-5-hydroxymethyl-3H- pyrrolo[4,3,2-gh]-l,4-benzodiazonin-3-one (13-N-octylindolactam G), may be prepared. 0 Alkylation of 4-aminoindole with methyl bromoacetate followed by acylation with octanoyl chloride in the presence of pyridine affords N-octanoyl-N-(4-indolyl)glycine methyl ester. This are converted to 13-N-octylindolactam G by the method described by A. Kozikowski et aL, op cit. The enantiomers are obtained separately by silica gel chromatography of the 14-O-[N-(S)-(l'-naphthyl)ethyl]carbamates followed by 5 reduction with trichlorosilane-triethylamine. Further modifications of this material to produce hydroxymethyl modified embodiments of this invention are carried out by the preparation of l-N-(t-butyloxycarbonyl)- 13-N-octylindolactam G, according to the method of Y. Endo et aL, Tetrahedron. 43, 2241-2247 (1987). Then, 14-O- methanesulfonyl-l-N-(t-butyloxycarbonyl)-13-N-octylindolactam G may be prepared by 0 treatment of the above indolactam with methanesulfonyl chloride. Treatment of this material with a variety of nucleophiles as described above followed by removal of the t- butyloxycarbonyl group by treatment with acid, for example trifluoroacetic acid in methylene chloride, affords a very wide variety of hydroxymethyl-modified derivatives. 14-Deoxy-14-(2'-hydroxyethylthio)-13-N-octylindolactam G and 14-deoxy-14- 5 (pentadecafluoro-[lH,lH]-octylthio)-13-N-octylindolactam G are specific illustrations of the types of useful compounds which may be prepared by application of these approaches. As a further illustration, 1,2-tetramethyleneindolactam V may be prepared. One of the many preparations of this parent uses 2-carbethoxy-4-nitroindole, which is a 0 side-product from the preparation of 4-nitroindole, as the starting material for transformation to 4-amino-l,2-tetramethyleneindole. Alkylation of the amino group of this compound with benzyl D-α-trifluoromethylsulfonyloxyisovalerate in the manner described by T. Kogan et al., op cit.. affords N-(l,2-tetramethyleneindol-4-yl)valine benzyl ester as a single enantiomer. This material may then be converted to 1,2- 5 tetramethyleneindolactam V by the methods described by A. Kozikowski et aL, op cit. Further modifications of this material to produce hydroxymethyl modified embodiments of this invention may be carried out by the techniques discussed above. As specific examples, 14-deoxy-14-(2'-hydroxyethylthio)- 1,2-tetramethyleneindolactam V and 14-deoxy- 14-(pentadecafluoro-[ 1 H, 1 H]-octylthio)- 1 ,2-tetramethyleneindolactam 0 V are prepared from 14-O-methanesulfonyl-l,2-tetramethyleneindolactam V. Further synthetic elaborations may be effected at the end or near the end of the preparation of the modified indolactam-parent or of the hydroxymethyl-modified indolactam. As one of many possible illustrations, 7-(2'-methylbut-3'-en-2'- yl)indolactam V (pendolmycin), which may be prepared by the method of Kozikowski et aL, op cit.. or by the method of Okabe et aL, Tetrahedron, 46, 5113-5120 (1990), or a derivative of pendolmycin, may be hydroborated. The resulting trialkylborane, or haloborane, may be converted into other functional groups including but not limited to hydroxy, carbonyl, alkyl, amino and halo, all by well-known methods such as those referenced by A. Pelter et aL, Borane Reagents, Academic Press, London, 1988. In a specific illustration, t-butyldimethylsilyl ether of pendolmycin may be prepared by treatment of a dimethylformamide solution of pendolmycin and imidazole (1:10 molar ratio) with t-butyldimethylchlorosilane. Treatment of this ether with 9- borabicyclo[3.3.1]nonane (9-BBN) affords the trialkylborane at the terminal carbon of the former terminal olefin, the oxidation of which with hydrogen peroxide in sodium hydroxide affords the primary alcohol. Acetylation of this alcohol with acetic anhydride in pyridine and removal of the silyl ether with tetrbutylammonium fluoride in tetrahydrofuran provides 7-(2'-methyl-4'-acetoxybutan-2'-yl)indolactam V. This may then be converted to 14-deoxy-14-(2"-hydroxyethylthio)-7-(2'-methyl-4'-hyroxybutan- 2'-yl)indolactam V or many other hydroxymethyl modified derivatives by the methods discussed above followed by treatment with sodium hydroxide in methanol to hydrolyze the acetate, yielding a hydroxy group amenable to a wide range of further transformations, preferably to establish a hydrophobic moiety in that position of the molecule. Similarly, compounds containing silicon and phosphorus may be obtained by adding reagents having Si-H or P-H bonds across the double bond of pendolmycin, for example, under the influence of chloroplatinic acid or light/peroxide catalysis, respectively. Such means for introducing silicon or phosphorus-containing groups may also be applied to structures having vinyl groups elsewhere in the molecule. For example, diethylphosphine may be added across the double bond of (-)-9- deshydroxymethyl-9-vinyl-7-octylindolactam V in a reaction promoted by light and peroxide catalysis to obtain 14-deoxy-14-diethylphosphinylmethyl-7-octylindolactam V. An illustration of the modification of the parent group after the introduction of appropriate hydroxymethyl modifications is the preparation of 14-deoxy-14- (pentadecafluoro-[ 1 H, 1 H]-octylthio)-7-[2'-methyl-4'-(N-octanoyl-N-ethyl)aminobutan- 2'-yl]indolactam V. Hydroboration of 14-deoxy-14-(pentadecafluoro-[lH,lH]- octylthio)pendolmycin, prepared in the manner discussed above from 14- methanesulfonylpendolmycin, with dichloroborane-dimethylsulfide in the presence of boron trifluoride provides 14-deoxy-14-(pentadecafluoro-[lH,lH]-octylthio)-7-(2'- methyl-4'-dichloroboranylbutan-2'-yl)indolactam V which upon treatment with ethylazide affords 14-deoxy-14-(pentadecafluoro-[lH, lH]-octylthio)-7-(2'-methyl-4'- ethylaminobutan-2'-yl)indolactam V, itself amenable to further reactions, for example acylation with octanoyl chloride to yield the more hydrophobic 14-deoxy-14- (pentadecafluoro-[lH,lH]-octylthio)-7-[2'-methyl-4'-N-octanoyl-N-ethyl)aminobutan- 2'-yl]indolactam V. The application of established techniques in the art of synthetic chemistry to naturally derived or to synthetically derived parents of the indolactam group also permits the obtainment of specifically modified parents of that class. These modified parents may then be further modified at the hydroxymethyl group by the methods discussed above. To illustrate this, 14-O-t-butlydimethylsilylindolactam V [Y. Endo et aL, Tetrahedron, 43, 2241-2247 (1987)] may be treated with sodium hydride in dimethylformamide followed by phosgene. The reactive chloroformamide so formed is quenched with perfluoroheptylmethanol to afford, after removal of the silyl ether, 1-N- (pentadecafluoro-[lH,lH]-octyloxy)carbonylindolactam V. By application of methods discussed above a variety of hydroxymethyl modified derivatives may be prepared as specifically illustrated by 14-deoxy-14-(2'-hydroxyethylthio)-l-N-(pentadecafluoro- [lH,lH]-octyloxy)carbonylindolactam V and by 14-deoxy-14-(pentadecafluoro- [ 1 H, lH]-octylthio)- l-N-(pentadecafluoro-[ 1 H, 1 H]-octyloxy)carbonylindolactam V. As a further illustration, 14-O-acetylindolactam V [K. Irie and K. Koshimizu, Mem. Coll. Agric, Kyoto Univ.. 132, 1-59 (1988)] may be alkylated with ethyl acrylate in the presence of sodium hydride to afford 14-O-acetoxy-l-N-(2'-carboethoxy)indolactam V. Treatment of this material with aluminum chloride in nitrobenzene followed by reduction of the purified product with lithium aluminum hydride-aluminum chloride in tetrahydrofuran provides 1,7-trimethyleneindolactam V. By application of methods discussed above a variety of hydroxymethyl modified derivatives may be prepared as specifically illustrated by 14-deoxy-14-(2'-hydroxyethylthio)- 1,7- trimethyleneindolactam V and by 14-deoxy-14-(pentadecafluoro-[lH,lH]-octylthio)- 1,7-trimethyleneindolactam V. Such specifically modified ^parents of the indolactam class may also be further modified at positions other than the hydroxymethyl group either before or after the modifications of hydroxymethyl group to produce embodiments of this invention. The means for accomplishing these modifications are obvious to someone with ordianry skill in organic synthesis. As an illustration, 7-(2'-aminoethyl)indolactam V may be prepared from indolactam V by methods similar to those described by K. Irie and K. Koshimizu, op cit. N-derivatization of this compound with pentadecafluoro-[lH,lH]- octyl isocyanate, 3-trimethylsilylpropanoyl chloride or 3- diphenyloxophosphinylpropanoyl chloride yields 7-[2'-(N'-pentadecafluoro-[lH,lH]- octylureido)ethyl]indolactam V, 7-[2'-(N-(3"- trimethylsilylpropanoyl)amino)ethyl]indolactam V or 7-[2'-(N-(3"- diphenyloxophosphinylpropanoyl)amino)ethyl]indolactam V respectively. By application of methods discussed above a variety of hydroxymethyl modified derivatives may be prepared as specifically illustrated by 14-deoxy-14-azido-7-[2'-(N'- pentadecafluoro-[lH,lH]-octylureido)ethyl]indolactam V, 14-deoxy-14-(2'- hydroxyethoxy)-7-[2'-(N-(3"-trimethylsilylpropanoyl)amino)ethyI]indolactam V, 14-O- [ 1 '(5'-hydroxynaphthyl)]-7-[2'-(N-(3"- diphenyloxophosphinylpropanoyl)amino)ethyl]indolactam V, 14-deoxy- 14-mercapto-7- [2'-(N'-pentadecafluoro-[lH,lH]-octylureido)ethyl]indolactam V, 14-deoxy-14- (pentadecafluoro-[ 1 H, 1 H]-octylthio)-7-[2'-(N-(3"- trimethyIsilylpropanoyl)amino)ethyl]indolactam V, and 14-deoxy-7-[2'-(N-(3"- diphenyloxophosphinylpropanoyl)amino)ethyl]indolactam V 14-sulfonic acid. As a further illustration, 14-O-acetyl-2-formyl-7-ethylindolactam V may be prepared by the treatment of 14-O-acetyl-7-ethylindolactam V with dichloromethyl methyl ether-titanium tetrachloride [K. Irie et aL, Int. J. Cancer. 43 513-519 (1989)]. Condensation with nitromethane followed by reduction of the nitrovinyl derivative with lithium aluminum hydride-aluminum chloride affords 2-(2'-aminoethyl)-7- ethylindolactam V. Derivatization of this compound with pentadecafluoro-[lH,lH]- octyl isocyanate, trimethylsilylpropanoyl chloride or 3- diphenyloxophosphinylpropanoyl chloride yields 7-ethyl-2-[2'-(N'-pentadecafluoro- [lH,lH]-octylureido)ethyl]indolactam V, 7-ethyl-2-[2'-(N-(3"- trimethylsilylpropanoyl)amino)ethyl]indolactam V or 7-ethyl-2-[2'-(N-(3"- diphenyloxophosphinylpropanoyl)amino)ethyl]indolactam V respectively. By application of methods discussed above a variety of hydroxymethyl modified derivatives may be prepared. Many parent phorboids of the diaminobenzyl alcohol (P3) class are available via total synthesis [see, for example, Wender, P. et aL, Proc Nat. Acad. Sci. 83, 4214-4218, 1986). Given the ready availability of a wide variety of precursors for phorboids of this class and for hydroxymethyl-modified members of that class, the means for producing the P -based compounds of this invention will be obvious to workers with ordinary skill in synthetic organic chemistry. For example, 4-carboxy-6-(N-decanoylamino)indole may be converted to its N- hydroxysuccinimide ester by reaction with one equivalent of dicyclohexylcarbodiimide and one equivalent of N-hydroxysuccinimide in acetonitrile/ tetrahydrofuran/methylene chloride suspension. The product N-hydroxysuccinimide ester is purified and then reacted with 3-amino-l,2-propanediol in tetrahydrofuran to obtain 4-(N-2,3-dihydroxypropylcarboxamido)-6-(N-decanoylamino)indole. Given the ready availability of a wide variety of precursors for phorboids of the diacylglycerol (P4) class and for hydroxymethyl-modified members of that class, the means for producing compounds of this invention based on the P4 parent phorboid class will be obvious to workers with ordinary skill in synthetic organic chemistry. In some cases these precursors will be available with suitable blocking groups in place or they may be put in place using well understood techniques or blocking groups are not needed. An illustration of the preparation of compounds of this invention is the preparation of 3R-3-carboxy-l,6-dioxo-2,5-dioxacyclotetracosane. Diesterification of readily available D-glyceric acid with 9-decynoyl chloride in the presence of pyridine affords 2,3-O,O-didecynoyl-D-glyceric acid. Treatment of this material with cupric acetate/pyridine affords the material coupled at the acetylenic termini, the catalytic hydrogenation of which affords 3R-3-carboxy-l,6-dioxo-2,5-dioxacyclotetracosane. In similar and related manner 2R-2,3-octanoyloxypropionic acid and 4R-4-carboxy-2,7- dioxo-3,6-dioxa-l,8-diazacyclocosane may be prepared. Furthermore, the same acylation with terminal acetylenic carboxylic acids followed by cyclization and reduction may be applied to l-chloro-2,3-dihydroxypropane, preceded or followed by displacement of the chloro leaving group with any of the nucleophilic type of reagents described above, to yield, after an appropriate sequence of protection-deprotection of chemically sensitive moieties in the intermediates, novel and useful hydroxymethyl- modified phorboids of the diacylglycerol class. Compounds of the polyacetate (Pg) class of phorboids may be obtained by semisynthetic modification of starting compounds purified from natural sources [see Mynderse, J. et aL, Science 196. 538-540 (1977) and references cited therein] or by adaptations and modifications of the intermediates or final products of total syntheses of the polyacetates [see Park, P. et al.. J. Am. Chem. Soc. 109. 6205-6207 (1987); Ireland, R. et al.. J. Am. Chem. Soc. 110. 5768-5779 (1988); and Nakamura, H. et aL, Proc. Nat. Acad. Sci. 8 9672-9676 (1989)]. This invention is illustrated further by the following examples. (This space was intentionally left blank.) SUBSTITUTE SHEET EXAMPLE 1 20-Deoxy-20-(2-hydroxyethylthio)phorbol 12.13-Dibutyrate One gram of sodium metal was dissolved in 50 ml methanol, and 0.044 ml of this solution was placed in a test tube. Then 2.63 grams distilled 2-mercaptoethanol was dissolved in 50 ml acetonitrile, and 0.044 ml of this solution was added to the test tube. Then 20 mg 20-deoxy-20-chlorophorbol 12,13-dibutyrate were dissolved in 0.25 ml acetonitrile in a capped, nitrogen-flushed test tube. This latter solution was then rapidly treated with the methoxide/mercaptoethanol solution. An immediate precipitate formed. After 7 minutes, the reaction was freed of solvent and treated with 1 ml water and 1 drop acetic acid. This residue was partitioned between water and ethyl acetate, followed by drying of the organic phase over sodium sulfate. Silica gel preparative liquid chromatography using hexane/ethyl acetate mixtures yielded 9.5 mg of 20-deoxy-20-(2-hydroxyethylthio)phorbol 12,13-dibutyrate, which could not be crystallized. EXAMPLE 2 20-Deoxy-20-(2-hydroxyethylthio)phorbol 12-Butyrate Further preparative liquid chromatography of the reaction mixture from Example 1 using hexane/ethyl acetate on siliza gel yielded 5.7 mg 20-deoxy-20-(2- hydroxyethylthio)phorbol 12-butyrate, the latter being the more polar compound. This compound could not be crystallized. EXAMPLE 3 20-Deoxy-20-(2-hydroxyethylthio)phorbol 12-Myristate 13-Acetate To 0.1 gram 20-deoxy-20-chlorophorbol 12-myristate 13-acetate in 1 ml acetonitrile was added 0.5 ml of a solution of 246 mg 2-mercaptoethanol and 436 mg 2,4,6- collidine in 10 ml acetonitrile, followed by 50 mg diisopropylethylamine in 0.2 ml acetonitrile and 0.1 ml t-butyl methyl ether. Ten minutes later the reaction was treated with 0.107 mmoles sodium methoxide and 0.225 mmoles 2-mercaptoethanol in 0.25 ml methanol. Five minutes later the proportion of sodium methoxide/mercaptoethanol was doubled. After 10 minutes the reaction was stopped by addition of 2 drops acetic acid and 0.5 ml water. The organics were extracted into ethyl acetate, washed once with water, and dried over sodium sulfate. After solvent removal, the crude residue was purified by preparative liquid chromatograhpy on silica gel using hexane/ethyl acetate 60/40. The product was 87 mg 20-deoxy-20-(2-hydroxyethylthio)-phorbol 12- myristate 13-acetate in high purity. The compound did not crystallize. EXAMPLE 4 20-Deoxy-20-(2-hydroxyethylthio)phorbol 12-Myristate Twenty-five mg of 20-deoxy-20-chlorophorbol 12-myristate 13-acetate was dissolved in 0.2 ml ethylene glycol and 0.2 ml acetonitrile. This solution was treated with 0.13 ml of a solution of 200 mg sodium metal in 20 ml ethylene glycol over a period of 40 minutes. The reaction was partitioned between water and ethyl acetate, and the separated organics were dried over sodium sulfate. After removal of the ethyl acetate, the crude 20-deoxy-20-chlorophorbol 12-myristate was dissolved in 0.8 ml acetonitrile and treated with 0.18 ml of a solution of 0.31 ml 2-mercaptoethanol, 0.5 ml acetonitrile, and 0.5 ml of 1% sodium in methanol. After 40 minutes, an additional 0.04 ml of 1% sodium in methanol was added. Ten minuted later the reaction was stopped with 1 drop of acetic acid. After removal of the solvents in a stream of nitrogen, the residue was partitioned between ethyl acetate and pH 8 potassium phosphate. The organics were dried over sodium sulfate and freed of solvent prior to preparative liquid chromatographic purification using silica gel and hexane/ethyl acetate 45/55. The product, 37 mg of 20-deoxy-20-(2-hydroxyethylthio)phorbol 12- myristate, could not be crystallized. EXAMPLE 5 20-Deoxy-20-r(2-hydroxyethyl)methylamino1phorbol 12-Myristate 13-Acetate 25 mg 20-deoxy-20-chlorophorbol 12-myristate 13-acetate was dissolved in 0.4 ml acetonitrile. To this was added 0.1 ml of a solution of 29.6 mg 2-(methylamino)ethanol in 1 ml acetonitrile. After 70 minutes and additional 0.1 ml of the same amine solution was added. After an additional 70 minutes, 0.2 ml more amine solution was added. After 6.6 hours of total reaction time, the reaction was diluted with 4 ml methylene chloride and subjected to preparative liquid chromatography on silica gel using methylene chloride/methanol 92/8 followed by repurification on silica gel using methylene chloride/methanol 96/4. The product, 20-deoxy-20-[(2- hydroxyethyl)methylamino]phorbol 12-myristate 13-acetate, 14 mg, could not be crystallized. SUBSTITUTE SHEET EXAMPLES 6. 7. and 8 20-Deoxy-20-fluorophorbol 12.13-Bis(2'.4'-difluorophenylacetate). 12-beta.l3-Bis-(2'.4'- difluorophenylacetoxy)-4,9-dihydroxy-l, 6(20),7-tigliatrien-3-one and 12-beta,13- Bis(2 , ,4'-difluorophenylacetoxy)-4,9-dihydroxy-7-fluoro-l,6(20)-tigliaden-3-one 100 mg of phorbol 12,13-bis(2',4 , -difluorophenylacetate) were dissolved in 1.5 ml methylene chloride and the solution was set at 0°C. Then 26.2 mg diethylaminosulfur trifluoride in 0.5 ml methylene chloride were added dropwise during 1 minute. After 40 minutes, 0.2 ml more diethylaminosulfur trifluoride was added. After 10 more more minutes, the reaction was shaken with 2 ml pH 8 potassium phosphate buffer, after which the organics were separated and dried over sodium sulfate. The reaction was repeated twice more, and the combined reaction products were freed of solvent, taken up in 10 ml ethyl acetate, and sucked through a funnel containing a layer of silica at the bottom, a layer of sodium sulfate in the middle and sodium chloride at the top. After washing the funnel contents with 50 ml ethyl acetate the combined eluants were freed of solvent and repeatedly chromatographed on silica preparative liquid chromatography columns using hexane/ethyl acetate 85/15 solvent mixtures. The products were 20-deoxy-20-fluorophorbol 12,13-bis(2',4'-difluorophenylacetate), 40 mg; 12-beta,13-bis-(2',4'-difluorophenylacetoxy)-4,9-dihydroxy-l, 6(20),7-tigliatrien-3- one, 25 mg; and 12-beta,13-bis(2',4'-difluorophenylacetoxy)-4,9-dihydroxy-7-fluoro- l,6(20)-tigliaden-3-one, 40 mg; none of which could be crystallized. EXAMPLE 9 4-Carboxy-6-(N-decanoylamino)indole Five hundred-fifteen mg of 4-carbomethoxy-6-(N-decanoylamino)indole [prepared by the method of Wender et al.. PNAS. 83. 4214-4218 (1986)] was dissolved in 60 mL of tetrahydrofuran. This solution was treated with 3 mL of a IN KOH solution in water and also with 5 mL of methanol. The mixture was heated at 80°C for 32 h. During this period another 2.5 mL of IN KOH was added in two portions. After cooling the mixture was concentrated in vacuo. The mixture was then diluted with water and acidified with concentrated hydrochloric acid. The mixture was then extracted with methylene chloride. The organic layers were dried over sodium sulfate and concentrated to afford 300 mg of 4-carboxy-6-(N-decanoylamino)indole (60% yield), mp 248-50°C. SUBSTITUTE SHEET EXAMPLE 10 4-Carboxy-6-(N-decanoylamino)indoIe N-succinimidyl ester A suspension of 470 mg of 4-carboxy-6-(N-decanoylamino)indole and 427 mg of N- hydroxysuccinimide in 100 mL of acetonitrile, 10 mL of methylene chloride and 10 mL of tetrahydrofuran was prepared. This suspension was stirred vigorously by a magnetic stirring bar as a solution of 540 mg of dicyclohexylcarbodiimide in 20 mL of acetonitrile was slowly added over a period of 1 h. The mixture was stirred vigorously for 72 h. It was then concentrated in vacuo and diluted with ethyl acetate. The resulting mixture was filtered to remove the copious precipitate. The filtrate was washed with water, dried over sodium sulfate and concentrated. Treatment of the resulting mixture with hexane/ethyl acetate 50:50 followed by filtration afforded 600 mg of 4-carboxy-6-(N-decanoylamino)indole N-succinimidyl ester, mp 154-5°C. EXAMPLE 11 4-(N-2,3-Dihydroxypropylcarboxamido)-6-(N-decanoylamino)indole To a solution of 89 mg of 3-amino-l,2-propanediol in 20 mL of tetrahydrofuran was added 136 mg of 4-carboxy-6-(N-decanoylamino)indole N-succinimidyl ester. The solution was stirred for 48 h. After concentration in vacuo the mixture was purified by preparative liquid chromatography using silica gel and methylene chloride/methanol 92:8. The product, 135 mg of 4-(N-2,3-dihydroxypropyIcarboxamido)-6-(N- decanoylamino)indole, was recrystalized from methanolmethylene chloride, mp 139- 41°C. EXAMPLE 12 4-(N-2-Mercaptoethylcarboxamido)-6-(N-decanoylamino indole and 4-(S-2- Aminoethylthiolcarboxy)-6-(N-decanoylamino indole To a solution of 113 mg of triethylamine in 20 mL of tetrahydrofuran was added, first, 86 mg of 2-aminoethanethiol hydrochloride and, then, 139 mg of 4-carboxy-6-(N- decanoylamino)indole N-succinimidyl ester. The solution was stirred for 48 h and then concentrated in vacuo. Purification by liquid chromatography using silica gel and methylene chloride/methanol 96:4 afforded two products. The earlier eluting product, 23 mg of 4-(N-2-mercaptoethylcarboxamido)-6-(N-decanoylamino)indole, decomposed at 200-5°C. The later eluting product, 22 mg of 4-(S-2-aminoethylthiolcarboxy)-6-(N- decanoylamino)indole, was recrystalized from methanol, mp 192-3°C. EXAMPLE 13 4-(2-Hydroxymethylpiperidinocarbonyl)-6-(N-decanoylamino)indole To a solution of 145 mg of 4-carboxy-6-(N-decylamino)-indole N-hydroxysuccinimidyl ester in 20 mL of tetrahydrofuran was added 103 mg or piperidinemethanol. The solution was heated at reflux for 5 days, at which time another 100 mg of piperidinemethanol was added and heating continued for another day. The solution was then concentrated in vacuo and purified by liquid chromatography using silica gel and methylene chloride/isopropyl alcohol (93:7). In this manner 21 mg of 4-(2- hydroxymethylpiperidinocarbonyl)-6-(N-decanoylamino)indole was obtained, M.P. 126-129°C. EXAMPLE 14 Phorbol 12-Myristate 13-Acetate 20-Methylcarbamate One hundred milligrams of phorbol 12-myristate 13-acetate was dissolved in 1 ml tetrahydrofuran. To this solution was added 11.5 microliters of methyl isocyanate, followed immediately by 20 microliters of a 10% by weight solution of dibutyltin dilaurate in tetrahydrofuran. After three hours an additional 11.5 microliters of methyl isocyanate was added. Sixteen hours later 30 microliters of the reaction solution was applied to a silica gel TLC plate and developed with hexanes/ ethyl acetate 46/54. The band at Rf 0.4 was scraped off and the product was eluted from the silica with acetone. Removal of the solvent in a stream of nitrogen gave 2.8 mg of phorbol 12-myristate 13-acetate 20-methylcarbamate as a glassy solid for spectroscopic analysis and bioassay. EXAMPLE 15 12-beta-Myristoyloxy-13-acetoxy-4.9-dihydroxy-7-hydroxymethyl-1.6(20)-tigliadien-3- one Ninety-eight mg of 20-deoxy-20-chlorophorbol 12-myristate 13-acetate was dissolved in 0.5 ml tetrahydrofuran. To this was added 0.15 ml saturated aqueous ammonium chloride, 0.15 ml 37% formalin solution, and 50 mg zinc dust (less than 325 mesh). The reaction was capped and shaken vigorously for 24 hours. At the end of this time the reaction was partitioned between pH8 phosphate buffer and ethyl acetate. The ethyl acetate phase was reduced to a volume of 2 ml under a stream of nitrogen and 0.125 ml was applied to a silica gel TLC plate and developed with hexanes/ethyl acetate 46/54. The band at Rf 0.45 was scraped off and the product was eluted from the silica powder with acetone. Removal of the acetone yielded 3.0 mg of 12-beta-myristoyloxy- 13-acetoxy-4,9-dihydroxy-7-hydroxymethyl-l,6(20)-tigliadien-3-one as a glassy solid for spectroscopic analysis and bioassay. EXAMPLE 16 A stock solution of 300 pmoles of the standard inflammatory compound phorbol 12- myristate 13-acetate per 0.005 ml acetone was prepared. This solution was used to prepare four-fold dilutions of 20-deoxy-20-(2-hydroxyethylthio)-phorbol 12-myristate 13-acetate, prepared as in Example 3, covering concentrations of the latter ranging from 4 to 64,000 pmoles per 0.005 ml. These solutions were used to demonstrate the anti-inflammatory activity of the latter compound by application of 0.005 ml to the insides of the right ears of mice, followed by the observation of ear inflammation/erythema during a 1-48 hour period. Inhibition of the phorbol 12- myristate 13-acetate induced inflammation was observed at the medium and higher concentrations of the inhibitor. In a like manner, the anti-inflammatory activities of the following other compounds are demonstrated: (i) phorbol 12-myristate; (ii) phorbol 12,13-diacetate; (iii) 20-deoxy-20-chlorophorbol 12-myristate 13-acetate; (iv) 20-deoxy-20-(2-hydroxyethylthio)phorbol 12,13-dibutyrate; (v) 20-deoxy-20-(2-hydroxyethylthio)phorbol 12-myristate 13-acetate; (vi) 20-deoxy-20-[(2-hydroxyethyl)methylamino]phorbol 12-myristate 13- acetate; (vii) 20-deoxy-20-fluorophorbol 12, 13-bis(2\4'-difluorophenylacetate; (viii) 12-beta,13-bis(2',4'-difluorophenylacetoxy)-4,9-dihydroxy-l,6(20),7- tigliatrien-3-one; (ix) 12-beta,13-bis(2',4'-difluorophenylacetoxy)-4,9-dihydroxy-7-fluoro-l,6(20)- tigliadien-3-one; (x) 12-beta-myristoyloxy 13-acetoxy-4,9-dihydroxy-7-hydroxymethyl-l,6(20)- tigliadien-3-one; and (xi) phorbol 12-myristate 13-acetate 20-methylcarbamate. (xϋ) 20-deshydoxy-20-carboxyphorbol 12,13-didecanoate; (xiii) 20-deshydoxy-20-carboxyphorbol 12-octyldimethylsilylacetate 13-(2',4'- difluorophenylacetate; (xiv) 20-deshydoxy-20-carboxyresiniferonol 9, 13, 14-orthophenylacetate; (xv) 20-deshydoxy-20-carboxyingenol 3-benzoate; (xvi) 6-deshydroxymethyl-20-carboxymethylidenephorboI 12,13-bis(2\4'- difluorophenylacetate; (xvii) -7-octyl-[9S,12S]-indolactam V 14-O-(N'-methylcarbamate); (xviii) (-)-l-(2'-triphenylphosphonium)ethyl-7-octylindolactam V 14-O-(N'- methylcarbamate); (xix) 9-deshydroxymethyl-9-carboxyindolactam V; (xx) (-)-14-deoxy-14-(3'-hydroxypropylthio)-7-octylindolactam V; (xxi) 20-deoxy-20-dimethylphosphinylphorbol 12-myristate 13-acetate; and (xxii) 20-deoxy-20-dimethylphosphonylphorbol 12-myristate 13-acetate. EXAMPLE 17 9-Deshydroxymethyl-9-carboxyindolactam V A solution of 60 g of 4-nitrogramine .B. Hester. J. Org. Chem.. 29, 1158 (1964)] and 54 g of ethyl nitroacetate in 1.2 L of chlorobenzene was heated at 100°C for 1.5 h. After cooling the mixture was filtered, washed with cold methylene chloride and dried in vacuo to afford 58.9 g of ethyl 3-(4-nitro-2-indolyl)-2-nitropropionate as a yellow solid: mp 159-160.5°C. Another 11 g may be recovered from the filtrate by dilution with hexane, preparative liquid chromatography [silica; methylene chloride/ethyl acetate (90:10)] and recrystalization from methanol. The structure was confirmed by NMR. To a solution of 7.29 g of ethyl 3-(4-nitro-2-indoIyl)-2-nitropropionate in 100 mL of tetrahydrofuran and 100 mL of ethanol was added 721 mg of 10% Pd on carbon. The resulting mixture was shaken in a Parr apparatus under about 50 psi hydrogen. After 70 min the mixture was filtered through celite and washed with ethanol. The filtrate was concentrated in vacuo. After purification by preparative liquid chromatography [silica; hexane/tetrahydrofuran (60:40)] 5.5 g of ethyl 3-(4-amino-2-indolyl)-2- nitropropionate was obtained as an off-white solid, mp 110-112°C. The structure was confirmed by NMR. To a mixture prepared by treatment of 8.6 g of the sodium salt of 3-methyI-2- oxobutanoic acid in 40 mL of dimethylformamide with 63 mmole of hydrogen chloride in 17 mL of dimethylformamide was added 10 g of ethyl 3-(4-amino-2-indolyl)-2- nitropropionate in 45 mL of N,N-dimethylformamide. After the resulting mixture had been cooled in an ice water bath, a solution of 6 g of sodium cyanoborohydride in 45 mL of N,N-dimethylformamide was added over 15 min. After the addition was complete, the mixture was allowed to warm to room temperature over a period of 30 min, at which time 200 mL of water was added and the mixture acidified with 2N hydrochloric acid. This solution was extracted with ethyl acetate. The organic layers were combined, washed with brine, dried over sodium sulfate and concentrated in vacuo and at a temperature only slightly above ambient to afford a crude mixture containing N-[4-[3-(2'-nitro-2'-carboethoxy)ethyl]indolyl]valine. To a cooled solution of this crude residue and 7.2 g of N-hydroxysuccinimide in 250 mL of acetonitrile was added 15.5 g of dicyclohexylcarbodiimide in 35 mL of acetonitrile. After 40 min, 2.7 mL of glacial acetic acid was added. After another 20 min the mixture was filtered and washed with ethyl acetate. The filtrates were washed with water and brine, dried over sodium sulfate and concentrated in vacuo to afford crude N-[4-[3-(2'-nitro-2'-carboethoxy)ethyl]indolyl]valine N-succinimidyl ester. After combination with another batch and purification by preparative liquid chromatography [silica; hexane/tetrahydrofuran (57:43)], 24.4 g (91% yield) of the ester was obtained as a gum. The structure was confirmed by NMR and mass spectra. To a solution of 3.75 g of N-[4-[3-(2'-nitro-2'-carboethoxy)ethyl]indolyl]valine N- succinimidyl ester in 200 mL of methanol was added 11.5 mL of a slurry of Raney nickel. This mixture was shaken on a Parr apparatus under about 50 psi of hydrogen for 35 min. The supernatant was removed by decantation and concentrated in vacuo. Several such crude mixtures were combined and purified by preparative liquid chromatography [silica; hexane/tetrahydrofuran (60:40)] to afford 3.23 g (31% yield) of N-desmethyl-9-deshydroxymethyl-9-carboethoxyindolactam V, mp 195-5°C (decomp), and 2.13 g (20.5% yield) of N-desmethyl-9-deshydroxymethyl-9-carboethoxy-epi- indolactam V, mp 206-8°C (decomp). The structures of these compounds were confirmed by NMR and mass spectra and by conversion to the known indolactam V and epi-indolactam V respectively. To a solution of 204 mg of N-desmethyl-9-deshydroxymethyl-9-carboethoxyindolactam V in 20 mL of acetonitrile containing 1.5 mL of water was added 400 μL of 37% aqueous formaldehyde. After 20 min, 182 mg of sodium cyanoborohydride was added. After the mixture had stirred at room temperature for 3 hours, phosphate buffer (pH 2) was added. The mixture was then concentrated in vacuo before rediluting with water and extracting with ethyl acetate. The organic layer was dried over sodium sulfate, filtered and concentrated in vacuo. The resulting solid was purified by preparative liquid chromatography [silica; hexane/tetrahydrofuran, (60:40)] to afford 167 mg of 9-deshydroxymethyl-9-carboethoxyindolactam V. The structure was confirmed by NMR and mass spectra. To a solution of 160 mg of 9-deshydroxymethyl-9-carboethoxyindolactam V in 23 mL of methanol was added 2.3 mL of 2N sodium hydroxide. After one hour 2N hydrochloric acid was added until the mixture was acidic whereupon it was concentrated to a small volume in vacuo. The residue was then diluted with water and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, filtered and concentrated in vacuo to afford 137 mg of 9-deshydroxymethyl-9- carboxyindolactam V as a white solid. EXAMPLE 18 9-Deshydroxymethyl-9-carboxy-epi-indolactam V A solution of 10 mg of N-desmethyl-9-deshydroxymethyl-9-carboethoxy-epi-indolactam V in 1 mL of acetonitrile containing 90 μL of water was added 20 μh of 37% aqueous formaldehyde. After 15 min 9 mg of sodium cyanoborohydride was added. After the mixture had stirred at room temperature for 3.5 hours, phosphate buffer (pH 2) was added and the mixture further diluted with water and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, filtered and concentrated in vacuo to afford crude 9-deshydroxymethyl-9-carboethoxy-epi-indolactam V. To a solution of 9-deshydroxymethyl-9-carboethoxy-epi-indolactam V in 2 mL of methanol was added 150 μL of 2N sodium hydroxide. After 50 min 2N hydrochloric acid was added until the mixture was acidic whereupon it was then diluted with water and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, filtered and concentrated in vacuo to afford a residue of 9-deshydroxymethyl-9- carboxy-epi-indolactam V. The structure was confirmed by conversion to 9- deshydroxymethyl-9-carbomethoxy-epi-indolactam V by treatment with a solution of diazomethane in ether. EXAMPLE 19 9-Deshydroxymethyl-9-carboxyindolactam V N-succinimidyl ester To a solution of 137 mg of 9-deshydroxymethyl-9-carboxyindolactam V and 66 mg of N-hydroxysuccinimide in 7 mL of acetonitrile was added 119 mg of dicyclohexylcarbodiimide in 3 mL of acetonitrile. After about one hour the reaction mixture was filtered and then concentrated in vacuo. Purification by preparative liquid chromatography [silica; hexane/tetrahydrofuran, (70:30)] afforded 136 mg of 9- deshydroxymethyl-9-carboxyindolactam V N-succinimidyl ester. EXAMPLE 20 9-Deshydroxymethyl-9-rN-(2'.3'-dihydroxy)propyll-carboxamidoindolactam V To 11 mg of 3-amino-l,2-propandiol and 1 mg of 4-dimethylaminopyridine was added 25 mg of 9-deshydroxymethyl-9-carboxyindolactam V N-succinimidyl ester in 250 μL of methylene chloride and 0.4 mL tetrahydrofuran. After 5 hr the mixture was concentrated in vacuo. After preparative liquid chromatography [silica; methylene chloride/isopropyl alcohol, (85:15); followed by ODS silica; acetonitrile/water, (33:67)], 10.5 mg of 9-deshydroxymethyl-9-[N-(2',3'-dihydroxy)propyl]-carboxamidoindolactam V and 3.4 mg of 9-deshydroxymethyl-9-[N-(2',3'-dihydroxy)propyl]-carboxamido-ιerji- indolactam V were obtained. The structures of these compounds were confirmed by mass spectra. EXAMPLE 21 9-Deshydroxymethyl-9-(2',3'-dihydroxy)carboxypropylindolactam V To 30 mg of glycerol and 1 mg of 4-dimethylaminopyridine was added 25 mg of 9- deshydroxymethyl-9-carboxyindolactam V N-succinimidyl ester in 250 μL of methylene chloride and 0.4 mL tetrahydrofuran. After 20 hr the mixture was concentrated in vacuo. After preparative liquid chromatography [silica; methylene chloride/isopropyl alcohol, (91:9); followed by ODS silica; acetonitrile/water, (36:64)] 13.3 mg of 9- deshydroxymethyl-9-(2',3'-dihydroxy)carboxypropylindoIactam V and 1.2 mg of 9- deshydroxymethyl-9-(2',3 , -dihydroxy)carboxypropyl-epi-indolactam V were obtained. The structures of these compounds were confirmed by mass spectra. EXAMPLE 22 9-Deshydroxymethyl-9-rN- ( 2'-glucosyl)1-carboxamidoindolactam V To 29 mg of 2-glucosamine hydrochloride, 19 mg of triethylamine and 1 mg of 4- dimethylaminopyridine was added 25 mg of 9-deshydroxymethyl-9-carboxyindolactam V N-succinimidyl ester in 250 μL of methylene chloride and 0.4 mL tetrahydrofuran. After 7.5 hr the mixture was concentrated in vacuo. After preparative liquid chromatography [silica; methylene chloride/methanol, (80:20); followed by ODS silica; acetonitrile/water (1.2% triethylamine), (21:79)], 12.4 mg of 9-deshydroxymethyl-9-[N- (2'-glucosyl)]-carboxamidoindolactam V and 2.4 mg of 9-deshydroxymethyl-9-[N-(2'- glucosyl)]-carboxamido-epj-indolactam V were obtained. EXAMPLE 23 In a similar manner the following compounds are prepared: (i) 9-deshydroxymethyl-9-[N-(2'-carboxy)ethyl)]carboxamidoindolactam V; (ii) 9-deshydroxymethyl-9-[N-(2'-hydroxy)ethyl)]carboxamidoindolactam V; (iii) 9-deshydroxymethyI-9-[S-(2'-hydroxy)ethyl)]thiacarboxyindolactam V; (iv) 9-deshydroxymethyl-9-(2'-hydroxy)carboxyethylindolactam V; (v) 9-deshydroxymethyl-9-[N-(2\3'-dihydroxy)propyl]-carboxamido-7- octylindolactam V; (vi) 9-deshydroxymethyl-9-[N-(2'-carboxy)ethyl)]carboxamido-7-octylindolactam V; (vii) 9-deshydroxymethyl-9-[N-(2'-hydroxy)ethyl)]carboxamido-7- octylindolactam V; (viii) 9-deshydroxymethyl-9-[S-(2'-hydroxy)ethyl)]thiacarboxy-7-octylindolactam V; (ix) 9-deshydroxymethyl-9-(2'-hydroxy)carboxyethyl-7-octylindolactam V; (x) 9-deshydroxymethyl-9-fN-(2',3'-dihydroxy)propyll-carboxamido-7-octyl-epi- indolactam V; (xi) 9-deshydroxymethyl-9-[N-(2'-carboxy)ethyl)]carboxamido-7-octyl-epi- indolactam V; (xii) 9-deshydroxymethyl-9-[N-(2'-hydroxy)ethyl)]carboxamido-7-octyl-epi- indolactam V; (xiii) 9-deshydroxymethyl-9-[S-(2'-hydroxy)ethyl)]thiacarboxy-7-octyl-epi- indolactam V; (xiv) 9-deshydroxymethyl-9-(2'-hydroxy)carboxyethyl-7-octyl-epi-indolactam V; (xv) 9-deshydroxymethyl-9-[N-(2',3'-dihydroxy)propyl]-carboxamido-6,7- tetramethyleneindolactam V; (xvi) 9-deshydroxymethyl-9-[N-(2'-carboxy)ethyl)]carboxamido-6,7- tetramethyleneindolactam V; (xvii) 9-deshydroxymethyl-9-[N-(2'-hydroxy)ethyl)]carboxamido-6,7- tetramethyleneindolactam V; (xviii) 9-deshydroxymethyl-9-[S-(2'-hydroxy)ethyl)]thiacarboxy-6,7- tetramethyleneindolactam V; (xix) 9-deshydroxymethyl-9-(2'-hydroxy)carboxyethyl-6,7- tetramethyleneindolactam V; (xx) 9-deshydroxymethyl-9-[N-(2\3'-dihydroxy)propyl]-carboxamido-7-octyl-12- desisopropyl- 12-benzylindolactam V; (xxi) 9-deshydroxymethyl-9-[N-(2'-carboxy)ethyl)]carboxamido-7-octyl- 12- desisopropyl-12-benzylindolactam V; (xxii) 9-deshydroxymethyl-9-[N-(2'-hydroxy)ethyl)]carboxamido-7-octyl-12- desisopropyl- 12-benzylindolactam V; (xxiii) 9-deshydroxymethyl-9-[S-(2'-hydroxy)ethyl)]thiacarboxy-7-octyl-12- desisopropyl-12-benzylindolactam V; and (xxiv) 9-deshydroxymethyl-9-(2'-hydroxy)carboxyethyl-7-octyl-12-desisopropyl- 12-benzylindolactam V. EXAMPLE 24 14-O-rN-(S)-(r-Naphthyl)ethyllcarbamoyl-7-octyl-(9S:12S)-indolactam V and 14-O-fN- (S 1 , -Naphthyl)ethvncarbamoyl-7-octyl-(9R.12R)-indolactam V To a solution of 139 mg of racemic 7-octylindolactam V [prepared as in K. Irie, et al., Agric Biol. Chem., 50, 2679 (1986)] in 15 mL of anhydrous tetrahydrofuran was added 56 mg of dibutyltin dilaurate and 48 mg of 4-dimethylaminopyridine in 3 mL of tetrahydrofuran. To this solution was added 445 mg of (S)-l-(l-napthyl)ethyl isocyanate in two portions over a two day period. The mixture was then concentrated in vacuo and the residue partitioned between water and ethyl acetate. The organic layer was dried over sodium sulfate and concentrated in vacuo. After preparative liquid chromatography [silica; hexane/tetrahydrofuran (75:25)], 200 mg of a mixture of diastereomers was obtained. Repetitive chromatography of this mixture [wet silica; hexane/wet ethyl acetate (65:35)] afforded 87 mg of pure 14-O-[N-(S)-(l'- naphthyl).ethyl]carbamoyl-7-octyl-(9S,12S)-indolactam V and 96 mg of pure 14-O-[N- (S)-(l'-naphthyl)ethyl]carbamoyl-7-octyl-(9R,12R)-indolactam V. The structures of these compounds were confirmed by reduction to the known (-)-7-octylindolactam V and (+)-7-octylindolactam V respectively. EXAMPLE 25 14-O-rN-(R)-(r-Naphthyl)ethyllcarbamoyl-(9S.12S)-indolactam V and 14-Q-ΓN-(R)-(1'- Naphthyl)ethyllcarbamoyl-(9R.12R)-indolactam V To a solution of 2.3 g of racemic indolactam V in 80 mL of anhydrous tetrahydrofuran with 569 mg of dibutyltin dilaurate and 560 mg of 4-dimethylaminopyridine was added 2.4 g of (R)-l-(l-napthyl)ethyl isocyanate. After stirring at room temperature for 24 hr, the mixture was concentrated in vacuo and the residue partitioned between water and ethyl acetate. The organic layer was dried over sodium sulfate and concentrated in vacuo. After preparative liquid chromatography [silica; hexane/tetrahydrofuran (55:45)], 3.65 g of a mixture of diastereomers was obtained. Repetitive chromatography of this mixture [wet silica; hexane/wet ethyl acetate (65:35)] afforded 1.92 g of 14-O-[N-(R)-(l'-naphthyl)ethyl]carbamoyI-(9R,12R)-indolactam V and 1.77 g of 14-O-[N-(R)-( -naphthyl)ethyl]carbamoyl-(9S,12S)-indolactam V. The structures of these compounds were confirmed by NMR, by comparison with a sample of 14-O-[N- (R)-( -naphthyl)ethyl]carbamoyl-(9S,12S)-indolactam V prepared from authentic (-)- indolactam V, and by reduction to the known (+)-indolactam V and (-)-indolactam V respectively. EXAMPLE 26 14-O-(N-Methylkarbamoyl-7-octyl-(9S.12S.-indoIactam V A solution of 3 mg of dibutyltin dilaurate and 2 mg of 4-dimethylaminopyridine in 0.5 mL of anhydrous tetrahydrofuran was added to 5 mg of (-)-7-octylindolactam V. Then 5 μL of methylisocyanate was added. After four hours at room temperature the mixture was concentrated under nitrogen and purified by preparative liquid chromatography [silica; hexane/tetrahydrofuran (70:30)] to afford 5 mg of 14-O-(N- methyl)carbamoyl-7-octyl-(9S, 12S)-indolactam V. EXAMPLE 27 rac-14-O-(N-Methyl)carbamoylindolactam V To a solution of 105 mg of racemic indolactam V, 41 mg of 4-dimethylaminopyridine, and 57 mg of dibutyltin dilaurate in 18 mL of anhydrous tetrahydrofuran was added 150 μL of methylisocyanate in two portions over 1.5 hr. One hour after the final SUBSTITUTE SHEET addition the mixture was concentrated in vacuo and the residue purified by recrystalization from tetrahydrofuran with hexane to afford 100 mg of rac-14-O-(N- methyl)carbamoylindolactam V, mp 184-185°C. EXAMPLE 28 In a similar manner the following compounds are prepared: (i) 14-O-(N-ethyl)carbamoylindolactam V; (ii) 14-O-(N-methyl)thiocarbamoylindolactam V; (iii) 14-O-(N-benzyl)carbamoylindolactam V; (iv) 14-O-(N-ethyl)carbamoyl-7-octylindolactam V; (v) 14-O-(N-methyl)thiocarbamoyl-7-octylindolactam V; (vi) 14-O-(N-benzyl)carbamoyl-7-octylindolactam V; (vii) 14-O-(N-methyl)carbamoyl-7-octyl-epi-indolactam V; (viii) 14-O-(N-ethyl)carbamoyl-7-octyl-epi-indolactam V; (ix) 14-O-(N-methyl)thiocarbamoyl-7-octyl-epi-indolactam V; (x) 14-O-(N-benzyl)carbamoyl-7-octyl-epi-indolactam V; (xi) 14-O-(N-methyl)carbamoyl-6,7-tetramethyleneindolactam V; (xϋ) 14-O-(N-ethyl)carbamoyl-6,7-tetramethyleneindolactam V; (xiii) 14-O-(N-methyl)thiocarbamoyl-6,7-tetramethyleneindolactam V; (xiv) 14-O-(N-benzyl)carbamoyl-6,7-tetramethyleneindolactam V; (xv) 14-O-(N-methyl)carbamoyl-7-octyl-12-desisopropyl-12-benzylindolactam V; (xvi) 14-O-(N-ethyl)carbamoyl-7-octyl- 12-desisopropyl- 12-benzylindolactam V; (xvii) 14-O-(N-methyl)thiocarbamoyl-7-octyl- 12-desisopropyl- 12- benzylindolactam V; (xviii) 14-O-(N-benzyl)carbamoyl-7-octyl- 12-desisopropyl- 12-benzylindolactam V; (xix) 14-O-(N-ethyl)carbamoylteleocidin B; (xx) 14-O-(N-methyl)thk)carbamoylteleocidin B; and (xxi) 14-O-(N-benzyl)carbamoylteleocidin B. EXAMPLE 29 rac-14-O- ( N-Methyl)carbamoyl-l-N-diphenylphosphoryl-indolactam V To 12 mg of rac-14-O-(N-methyl)carbamoylindolactam V in 500 μL of anhydrous tetrahydrofuran was added approximately 2 mg of sodium hydride (50% dispersion in oil) followed by 30 μL of diphenyl chlorophosphate in two portions. After 2-3 hours, SUBSTITUTE SHEET thin layer chromatographic analysis [silica; methylene chloride/methanol (95:5)] showed that the starting rac-14-O-(N-methyl)carbamoylindolactam V had been converted to rac-14-O-(N-methyl)carbamoyl-l-N-diphenylphosphoryl-indolactam V with R f =0.43. EXAMPLE 30 rac-14-O-(N-Methyl)carbamoyl-l-N-(2-triphenylphosphonium)-ethylindolactam V. Methanesulfonate salt To 16 mg of rac- 14-O-(N-methyl)carbamoyIindolactam V in 0.75 mL of N,N- dimethylformamide in an ice-water bath was added 8 mg of sodium hydride (60% dispersion in oil). After about 10 min this solution was added to 20 mg of 2- methanesulfonyloxyethyltriphenylphosphonium bromide (prepared from 2- hydroxyethyltriphenylphosphonium bromide). After 1 hr this mixture was concentrated in vacuo. The residue was partioned between ethyl acetate and phosphate buffer (pH 2). The organic layer was dried over sodium sulfate and concentrated in vacuo. The crude mixture was taken up in methanol, treated with a small amount of methansulfonic acid in methanol and reconcentrated. Thin layer chromatographic analysis [silica; methylene chloride/methanol (90:10)] showed that the starting rac- 14-O-(N-methyl)carbamoylindolactam V had been converted to r,ac-14-O-(N-methyl)carbamoyl-l-N-(2-triphenylphosphonium)ethylindolactam V, methanesulfonate salt, with Rf=0.57. EXAMPLE 31 In a similar manner the following compounds are prepared; (i) 14-O-(N-methyl)thiocarbamoyl-I-N-(2- triphenylphosphonium)ethylindolactam V, methanesulfonate salt; (ii) 14-O-(N-benzyl)carbamoyI-l-N-(2-triphenylphosphonium)ethylindolactam V, methanesulfonate salt; (iii) 14-O-(N-methyl)thiocarbamoyl-l-N-(2-triphenylphosphonium)ethyl-epi- indolactam V, methanesulfonate salt; (iv) 14-O-(N-benzyl)carbamoyl-l-N-(2-triphenylphosphonium)ethyl-epi- indolactam V, methanesulfonate salt; (v) 14-O-(N-methyl)carbamoyl-l-N-(2-triphenylphosphonium)ethyl-epi- indolactam V, methanesulfonate salt; (vi) 14-O-(N-methyl)carbamoyl-l-N-(2-triphenylphosphonium)ethyl- 12- desisopropyl- 12-benzylindolactam V, methanesulfonate salt; (vii) 14-O-(N-methyl)thiocarbamoyl-l-N-(2-triphεnylphosphonium)ethyl-12- desisopropyl- 12-benzylindolactam V, methanesulfonate salt; and (viii) 14-O-(N-benzyl)carbamoyl-l-N-(2-triphenylphosphonium)ethyl-12- desisopropyl- 12-benzylindolactam V, methanesulfonate salt. EXAMPLE 32 rac-14-O-(N-Methyl)carbamoyl-l-N-trimethylsilymethyl-indolactam V To 16 mg of rac-14-O-(N-methyl)carbamoylindolactam V in 0.75 mL of N,N- dimethylformamide in an ice-water bath was added 8 mg of sodium hydride (60% dispersion in oil). After about 10 min, 20 μL of bromomethyltrimethylsilane was added. After I hr this mixture was concentrated in vacuo and the residue partitioned between ethyl acetate and phosphate buffer (pH 8). The organic layer was dried over sodium sulfate and concentrated in vacuo. Thin layer chromatographic analysis [silica; methylene chloride/methanol (95:5) showed that the starting rac-14-O-(N- methyl)carbamoylindolactam V had been converted to rac-14-O-(N- methyl)carbamoyl-l-N-trimethylsilylmethyl-indolactam V with EXAMPLE 33 In a similar manner the following compounds are prepared: (i) 14-O-(N-methyl)thiocarbamoyl-l-N-trimethylsilylmethylindolactam V; (ii) 14-O-(N-benzyl)carbamoyl- 1-N-trimethylsilylmethylindolactam V; (iii) 14-O-(N-methyl)carbamoyl- 1-N-trimethylsilylmethyl-epi-indolactam V; (iv) 14-O-(N-methyl)thiocarbamoyl- 1-N-trimethylsilylmethyl-egi-indolactam V; (v) 14-O-(N-benzyl)carbamoyl-l-N-trimethylsilylmethyl-epi-indolactam V; (vi) 14-O-(N-methyl)carbamoyl-l-N-trimethylsilylmethyl-12-desisopropyl-12- benzylindolactam V; (vii) 14-O-(N-methyl)thiocarbamoyl-l-N-trimethylsilylmethyl-12-desisopropyl- 12-benzylindolactam V; and (viii) 14-O-(N-benzyl)carbamoyl-l-N-trimethylsilylmethyl-12-desisopropyl-12- benzylindolactam V. EXAMPLE 34 14-Q-f (Diisopropylamino)methoxylphosphinyl-7-octyl-(9S, 12S)-indolactam V To 5 mg of (-)-7-octylindolactam V in 180 L of anhydrous methylene chloride was added 15 L of diisopropylethylamine followed by 7 L of N,N- diisopropylmethylphosphoramidic chloride. After 0.5 hr, thin layer chromatographic analysis [silica; hexane/ethyl acetate (45:55)] showed that the starting (-)-7- octylindolactam V had been converted to 14-O- [(diisopropylamino)methoxy]phosphinyl-7-octyl-(9S,12S)-indolactam V with Rf=0.72. EXAMPLE 35 14-O-(Dimethyl)thiophosphoryl-7-octyl-(9S,12S)-indolactam V To 5 mg of (-)-7-octylindolactam V in 200 μL of anhydrous methylene chloride and containing 5 μL of pyridine was added 14 L of dimethyl chlorothiophosphate and approximately 10 mg of 4-dimethylaminopyridine. After 2 hr, thin layer chromatographic analysis [silica; methylene chloride/methanol (95:5)] showed that the starting (-)-7-octylindolactam V (Rr=0.32) had been converted to 14-O- (dimethyl)thioρhosphoryl-7-octyl-(9S,12S)-indolactam V with EXAMPLE 36 In a similar manner the following compounds are prepared: (i) 14-O-(dimethyl)phosphorylindolactam V; (ii 14-O-(tetramethyl)phosphorodiamidylindolactam V; (iii) 14-O-(diethyl)phosphonylindolactam V; (iv) 14-O-[bis(2',2',2'-trichloroethyl)]phosphorylindolactam V; (v) 14-O-(dimethyl)thiophosphorylindolactam V; (vi) 14-O-(dimethyl)phosphoryl-7-octylindolactam V; (vii) 14-O-(tetramethyl)phosphorodiamidyl-7-octylindolactam V; (viii) 14-O-(diethyl)phosphonyl-7-octylindolactam V; (ix) 14-O-[bis(2',2 , ,2'-trichloroethyl)]phosphoryl-7-octylindolactam V; (x) ' J4-O-(dimethyl)thiophosphoryl-7-octyl-epi-indolactam V; (xi) 14-O-(dimethyl)phosphoryl-7-octyl-epi-indolactam V; (xii) 14-O-(tetramethyl)phosphorodiamidyl-7-octyl-epi-indolactam V; (xiii) 14-O-(diethyl)phosphonyl-7-octyl-epi-indolactam V; (xiv) 14-O-[bis(2',2',2'-trichloroethyl)1phosphoryl-7-octyl-epi-indolactam V; (xv) 14-O-(dimethyl)phosphoryl-6,7-tetramethyleneindolactam V; SUBSTITUTE SHEET (xvi) 14-O-(tetramethyl)phosphorodiamidyl-6,7-tetramethyleneindolactam V; (xvii) 14-O-(diethyl)phosphonyl-6,7-tetramethyleneindolactam V; (xviii) 14-O-[bis(2',2',2'-trichloroethyl)]phosphoryl-6,7- tetramethyleneindolactam V; (xix) 14-O-(dimethyl)thiophosphoryl-6,7-tetramethyleneindolactam V; (xx) 14-O-(dimethyl)thiophosphoryl-7-octyl- 12-desisopropyl- 12- benzylindolactam V; (xxi) 14-O-(dimethyl)phosphoryl-7-octyl-12-desisopropyl-12-benzylindolactam V; (xxii) 14-O-(tetramethyl)phosphorodiamidyl-7-octylindolactam V; (xxiii) 14-O-(diethyl)phosphonyl-7-octyl- 12-desisopropyl- 12-benzylindolactam V; (xxiv) 14-O-[bis(2',2',2'-trichloroethyl)]phosphoryl-7-octyl-12-desisopropyl-12- benzylindolactam V; (xxv) 14-O-(dimethyl)phosphorylteleocidin B; (xxvi) 14-O-(tetramethyl)phosphorodiamidylteleocidin B; (xvii) 14-O-(diethyl)phosphonylteleocidin B; (xxviii) 14-O-[bis(2'2',2'-trichloroethyl)]phosphorylteleocidin B; and (xxix) 14-O-(dimethyl)thiophosphorylteleocidin B. EXAMPLE 37 14-Deoxy-14-(3'-hydroxy propylthio-7-octyl-(9S.12S')-indolactam V To a solution of 6 mg of 3-mercapto-l-propanol in 150 μL of methanol containing 1.3 mg of sodium methoxide was added approximately 6 mg of 14-O-methanesulfonyl-7- octyl-(9S,12S)-indolactam V (prepared from (-)-7-octylindolactam V) in 300 μL of acetonitrile. After 20 hr this mixture was diluted with ethyl acetate and washed twice with phosphate buffers (pH 2 and pH 8). After drying over sodium sulfate, the organic layer was concentrated under a nitrogen stream. Thin layer chromatographic analysis [silica; methylene chloride/methanol (96:4)] showed that the starting 14-O- methanesulfonyl-7-octyl-(9S,12S)-indolactam V had been converted to 14- deoxy-14-<3'-hydroxy)propylthio-7-octyl-(9S,12S)-indolactam V with R f =0.22. EXAMPLE 38 In a similar manner the following compounds are prepared: (i) 14-deoxy-14-butylthio-7-octylindolactam V; SUBSTITUTE SHEET (ii) 14-deoxy- 14-(2'-hydroxy- 1 '-methyl)ethylthio-7-octylindolactam V; (iii) 14-deoxy- 14-(2'-carboxy)ethylthio-7-octylindolactam V; (iv) 14-deoxy- 14-(2'-amino)ethylthio-7-octylindolactam V; (v) 14-deoxy- 14-(3'-hydroxymethyl)phenylthio-7-octylindolactam V; (vi) 14-deoxy- 14-propylthio-7-octyl-eβ]-indolactam V; (vii) 14-deoxy- 14-(2'-hydroxy- 1 '-methyl)ethylthio-7-octyl-epi-indolactam V; (viii) 14-deoxy- 14-(2'-carboxy)ethylthio-7-octyl-epi-indolactam V; (ix) 14-deoxy- 14-(2'-amino)ethylthio-7-octyl-epi-indolactam V; (x) 14-deoxy- 14-(3'-hydroxymethyl)phenylthio-7-octyl-epi-indolactam V; (xi) 14-deoxy-14-(2'-hydroxy)ethylthio-7-octyl-epi-indolactam V; (xii) 14-deoxy- 14-propylthio-6,7-tetramethyIeneindolactam V; (xiii) 14-deoxy-14-(2'-hydroxy- -methyl)ethylthio-6,7-tetramethyleneindolactam V; (xiv) 14-deoxy-14-(2'-carboxy)ethylthio-6,7-tetramethyleneindolactam V; (xv) 14-deoxy- 14-(2'-amino)ethylthio-6,7-tetramethyleneindolactam V; (xvi) 14-deoxy- 14-(3'-hydroxymethyl)phenylthio-6,7-tetramethyleneindolactam V; (xvii) 14-deoxy- 14-(2'-hydroxy)ethylthio-6,7-tetramethyleneindolactam V; (xviii) 14-deoxy- 14-propylthio-7-octyl- 12-desisopropyl- 12-benzylindolactam V; (xix) 14-deoxy-14-(2'-hydroxy-r-methyl)ethylthio-7-octyl-12-desisopropyl-12- benzylindolactam V; (xx) 14-deoxy-14-(2'-carboxy)ethylthio-7-octyl-12-desisopropyl-12- benzylindolactam V; (xxi) 14-deoxy- 14-(2'-amino)ethylthio-7-octyl- 12-desisopropyI- 12- benzylindolactam V; (xxii) 14-deoxy-14-(3'-hydroxymethyl)phenylthio-7-octyl-12-desisopropyl-12- benzylindolactam V; (xxiii) 14-deoxy-14-(2'-hydroxy)ethylthio-7-octyl-12-desisopropyl-12- benzylindolactam V; (xxiv) 14-deoxy-14-propylthioteleocidin B; (xxv) 14-deoxy-14-(2'-hydroxy- -methyl)ethylthioteleocidin B; (xxvi) 14-deoxy-14-(2'-carboxy)ethylthioteleocidin B; (xxvii) 14-deoxy-14-(2'-amino)ethylthioteleocidin B; (xxviii) 14-deoxy- 14-(3'-hydroxymethyl)phenylthioteleocidin B; and (xxix) 14-deoxy- 14-(2'-hydroxy)ethylthioteleocidin B. EXAMPLE 39 14-Deoxy-14-(N-methanesulfonyl)amino-7-octyl-(9S.12S)-indolactam V To a solution of 4 mg of methanesulfonamide in 150 μL of methanol containing 1.3 mg of sodium methoxide was added approximately 6 mg of 14-O-methanesulfonyl-7- octyl-(9S,12S)-indolactam V (prepared from (-)-7-octylindolactam V) in 300 μL of acetonitrile. After 26 hr this mixture was diluted with ethyl acetate and washed twice with phosphate buffers (pH 2 and pH 8). After drying over sodium sulfate, the organic layer was concentrated under a nitrogen stream. Thin layer chromatographic analysis [silica; hexane/ethyl acetate (45:55)] showed that the starting 14-O-methanesulfonyl-7- octyl-(9S,12S)-indolactam V had been converted to 14-deoxy- 14-N- methanesulfonyl)amino-7-octyl-(9S,12S)-indolactam V with EXAMPLE 40 14-Deoxy-14-trimethylphosphonium-7-octyl-(9S.12S)-indolactam V. Methanesulfonate salt To a solution of approximately 6 mg of 14-O-methanesulfonyl-7-octyl-(9S,12S)- indolactam V (prepared from (-)-7-octylindolactam V) in 300 μL of acetonitrile was added 30 μL of 1M trimethylphosphine in toluene. After 26 " hr this mixture was concentrated under a nitrogen stream. Thin layer chromatographic analysis [silica; methylene chloride/methanol, (95:5)] showed that the starting 14-O-methanesulfonyl- 7-octyl-(9S,12S)-indolactam V had been converted to 14-deoxy-14- trimethylphosphonium-7-octyl-(9S,12S)-indolactam V, methanesulfonate salt, with R f =0.07. EXAMPLE 41 14-Deoxy-14-triphenylphosphonium-7-octyl-(9S.12S)-indolactam V, Iodide salt To a solution of approximately 5 mg of 14-deoxy- 14-iodo-7-octyl-(9S,12S)-indolactam V (prepared from 14-O-methanesulfonyl-7-octyl-(9S,12S)-indolactam V) in 1 mL of tetrahydrofuran was added 6 mg of triphenyphosphine. After 2.5 hr this mixture was concentrated under a nitrogen stream. Thin layer chromatographic analysis [silica; hexane/ethyl acetate, (45:55)] showed that the starting 14-deoxy- 14-iodo-7-octyl- SUBSTITUTE SHEET (9S, 12S)-indolactam V had been converted to 14-deoxy-14- triphenylphosphonium-7-octyl-(9S,12S)-indoIactam V, iodide salt, with EXAMPLE 42 In a similar manner the following compounds are prepared: (i) 14-deoxy-14-tributylphosphonium-7-octylindolactam V, iodide salt; (ii) 14-deoxy- 14-triethylphosphonium-7-octylindolactam V, iodide salt; (fii) 14-deoxy- 14-methyldiphenylphosphonium-7-octylindolactam V, iodide salt; (iv) 14-deoxy- 14-trimethylphosphonium-7-octyl-eri-indolactam V, iodide salt; (v) 14-deoxy- 14-tributylphosphonium-7-octyl-ep_i-indolactam V, iodide salt; (vi) 14-deoxy- 14-triethylphosphonium-7-octyl-epi-indolactam V, iodide salt; (vii) 14-deoxy- 14-methyldiphenylphosphonium-7-octyl-epi-indolactam V, iodide salt; (viii) 14-deoxy- 14-trimethylphosphonium-6,7-tetramethyleneindolactam V, iodide salt; (ix) 14-deoxy-14-tributylphosphonium-6,7-tetramethyleneindolactam V, iodide salt; (x) 14-deoxy- 14-triethylphosphonium-6,7-tetramethyleneindolactam V, iodide salt; (xi) 14-deoxy- 14-methyldiphenylphosphonium-6,7-tetramethyleneindolactam V, iodide salt; (xii) 14-deoxy-14-tributylphosphonium-7-octyl-12-desisopropyl-12- benzylindolactam V, iodide salt; (xiii) 14-deoxy-14-triethylphosphonium-7-octyl-12-desisopropyl-12- benzylindolactam V, iodide salt; (xiv) 14-deoxy-14-methyldiphenylphosphonium-7-octyl-12-desisopropyl-12- benzylindolactam V, iodide salt; (xv) 14-deoxy-14-trimethylphosphonium-7-octyl-12-desisopropyl-12- benzylindolactam V, iodide salt; (xvi) 14-deoxy- 14-tributylphosphoniumteIeocidin B, iodide salt; (xvii) 14-deoxy- 14-triethylphosphoniumteleocidin B, iodide salt; (xviii) 14-deoxy- 14-methyldiphenylphosphoniumteleocidin B, iodide salt; and (xix) 14-deoxy- 14-trimethylphosphoniumteIeocidin B, iodide salt. EXAMPLE 43 14-Deoxy-14-trimethylsilvI-7-octyl-(9S.12S -indolactam V SUBSTITUTE SHEET To a mixture of 10 mg of powdered zinc and 10 μL of trimethylchlorosilane in 300 μL of anhydrous tetrahydrosilane was added approximately 5 mg of 14-deoxy- 14-iodo-7- octyl-(9S,12S)-indolactam V (prepared from 14-O-methanesulfonyl-7-octyl-(9S,12S)- indolactam V) in 500 μL of tetrahydrofuran. After 2.5 hr, thin layer chromatographic analysis [silica; hexane/ethyl acetate, (45:55)] showed that the starting 14-deoxy-14- iodo-7-octyl-(9S,12S)-indolactam V had been largely converted to 14-deoxy- 14-trimethylsilyl-7-octyl-(9S,12S)-indolactam V with R f =0.49. EXAMPLE 44 In a similar manner the following compounds are prepared: (i) 14-deoxy- 14-trimethylsilyl-7-octyl-erji-indolactam V; (ii) 14-deoxy-14-trimethylsilyl-7-octyl-12-desisopropyl-12-benzylindolactam V; (iii) 14-deoxy- 14-trimethylsilyl-6,7-tetramethyleneindolactam V; and (iv) 14-deoxy-14-trimethylsilylteleocidin B. EXAMPLE 45 20-Deoxy-20-hydroximinophorbol 12.13-Bis(2',4 , -difluorophenylacetate) and 20- Deoxy-3-deoxo-3,20-bis(hydroximino)phorbol 12.13-Bis(2',4'-difluorophenylacetate) To a solution of 250 mg of 20-deoxy-20-oxophorbol 12,13-bis(2',4'- difluorophenylacetate) [G. Kreibich and E. Hecker, Z. Krebsforsch.. 74, 448-456 (1970)] in 6 mL of methanol was added 4 mL of a solution prepared by adding 40 mL of 0.375 M sodium methoxide in methanol to 2.5 g of hydroxylamine hydrochloride. After 2.5 hr the mixture was concentrated in vacuo and the residue was partitioned between water and ethyl acetate. The organic layer was filtered through through a funnel containing layers of sodium chloride, sodium sulfate and silica gel (N/N/S) and concentrated in vacuo. After purification of the residue by preparative liquid chromatography [silica; methylene chloride/ethyl acetate (85:15)], 211 mg of 20-deoxy- 20-hydroximinophorbol 12,13-bis(2',4'-difluorophenylacetate) and 27 mg of 20-deoxy- 3-deoxo-3,-20-bis(hydroximino)phorbol 12, 13-bis(2',4'-difluorophenylacetate) were obtained. The structures were confirmed by NMR and mass spectra. EXAMPLE 46 In a similar manner the following compounds are prepared: (i) 20-deoxy-20-hydroximinophorbol 12,13-didecanoate; (ii) 20-deoxy-20-hydroximinophorbol 12,13-dibutyrate; (iii) 12,20-dideoxy-20-hydroximinophorbol 13-decanoate; (iv) 12,20-dideoxy-20-hydroximinophorbol 13-(2',4'-difluorophenyl)acetate; 5 (v) 20-deoxy-20-hydroximinophorbol 12-myristate 13-acetate; and (vi) 20-deoxy-3-deoxo-3,20-bis(hydroximino)phorbol 12-myristate 13-acetate. EXAMPLE 47 10 20-Deoxy-20-methoximinoρhorbol 12.13-Bis(2'.4'-difluorophenylacetate) and 20- Deoxy-3-deoxo-3,20-bis(methoximino)phorbol 12,I3-Bis(2',4'-difluorophenylacetate) To a solution of 100 mg of 20-deoxy-20-oxophorbol 12,13-bis(2',4'- difluorophenylacetate) in 1 mL of pyridine was added 35 mg of methoxylamine 15 hydrochloride. After 2.5 hr the mixture was partitioned between ethyl acetate and phosphate buffer (pH 2). The organic layer was washed with phosphate buffer (pH 8), filtered through N/N/S and concentrated in vacuo. After preparative liquid chromatography [silica; hexane/ethyl acetate (80:20)] of the residue, 96 mg of 20- deoxy-20-methoximinophorbol 12,13-bis(2',4'-difluorophenylacetate) and 4 mg of 20- 20 deoxy-3-deoxo-3,20-bis(methoximino)phorbol 12, 13-bis(2',4'-difluorophenylacetate) were obtained. The structures were confirmed by NMR and high resolution mass spectra. EXAMPLE 48 25 In a similar manner the following compounds are prepared: (i) 20-deoxy-20-hydroximinophorbol 12-(3-phenoxy)benzoate 13-butyrate; (ii) 20-deoxy-20-hydroximinophorbol 12-(3,5-difluorophenyl)acetate 13-(3,4- difluorobenzoate); 30 (iϋ) 20-deoxy-20-hydroximinophorbol 12-(3,5-difluorocinnamate) 13-[3-(2',4'- difluorophenyl)propionate]; (iv) 20-deoxy-20-hydroximinophorbol 1 , 13-bis(2,4-dichlorophenylacetate); (v) 20-deoxy-20-methoximinophorbol 12,13-didecanoate; (vi) 12,20-dideoxy-20-methoximinophorbol 13-decanoate; 35 (vii) 20-deoxy-20-t-butoximinophorbol 12-myristate 13-acetate; (viii) 20-deoxy-20-carboxymethoximinophorbol 12,13-bis(2',4'- difluorophenylacetate); (ix) 20-deoxy-20-(4-nitrobenzoximino)phorbol 12,13-bis(2',4'- difluorophenylacetate); 40 (x) 20-deoxy-20-alloximinophorbol 12-myristate 13-acetate; and (xi) 20-deoxy-20-oxophorbol 12,13-bis(2',4'-difluorophenylacetate) 20- semicarbazone. EXAMPLE 49 6-Deshydroxymethyl-6-cyanophorbol 12.13-Bis(2'.4'-difluorophenylacetate) A solution of 100 mg of 20-deoxy-20-hydroximinophorbol 12,13-bis(2',4'- difluorophenylacetate) in 0.5 mL pyridine was added to a mixture of 9 mg cupric sulfate and 35 mg of triethylamine in 1.5 mL of methylene chloride. After 1 hr 47 mg of dicyclohexylcarbodiimide was added to the green solution. After 3 hr at room temperature the reaction mixture was heated at 40-45°C for 3 hr. During this period another 50 mg of dicyclohexylcarbodiimide was added. After cooling the mixture to room temperature, 0.5 mL of formic acid was added followed by partitioning between ethyl acetate and phosphate buffer (pH 2). The organic layer was washed with phosphate buffer (pH 8), filtered through N/N/S and concentrated in vacuo. Preparative liquid chromatography [silica; hexane/ethyl acetate (75:25)] afforded 43 mg of 6-deshydroxymethyl-6-cyanophorbol 12, 13-bis(2',4'-difluorophenylacetate) . The structure was confirmed by NMR and high resolution mass spectra. EXAMPLE 50 In a similar manner the following compounds are prepared: (i) 6-deshydroxymethyl-6-cyanophorbol 12-(3,5-difluorophenyl)-acetate 13-(3,4- difluorobenzoate); (ii) 6-deshydroxymethyl-6-cyanophorbol 12,13-didecanoate; and (iii) 12-deoxy-6-deshydroxymethyl-6-cyanophorbol 13-decanoate. EXAMPLE 51 6-Deshydroxymethyl-6-carboxyphorbol 12.13-Bis(2 > .4 , -difluorophenylacetate To a solution of 1.51 g of 20-deoxy-2-oxo-phorbol 12,13-bis(2',4'- difluorophenylacetate) in 55 mL of methylene chloride, 150 mL of t-butyl alcohol and 10 mL of 2-methyl-2-butene was added 18.75 mL of a solution prepared by dissolving 1.99 g of sodium chlorite and 2 g of potassium dihydrogen phosphate in 20 mL of deionized water. After 1.25 hr about 10 mL of 20% aq. sodium thiosulfate was added and the mixture was partially concentrated in vacuo. The residue was partitioned between ethyl acetate and phosphate buffer (pH 8). The organic layer was washed sequentially with pH 2 and pH 8 phosphate buffers and dried over sodium sulfate. After concentration in vacuo, 1.53 g of 6-deshydroxymethyl-6-carboxyphorbol 12,13- bis(2\4'-difluorophenylacetate) was obtained. An analytical sample was obtained by preparative liquid chromatography [silica; methylene chloride/methanol (95:5)] and the structure confirmed by NMR and mass spectra. EXAMPLE 52 In a similar manner the following compounds are prepared: (i) 6-deshydroxymethyl-6-carboxyphorbol 12,13-dibutyrate; (ii) 6-deshydroxymethyl-6-carboxyphorbol 12,13-didecanoate; (iii) 6-deshydroxymethyl-6-carboxy-3-deoxo-3-benzoyloxyphorbol 12-butyrate 13-(2',4'-difluorobenzoate); (iv) 6-deshydroxymethyl-6-carboxy-3-deoxo-3-(2\4'- difluorophenylacetoxy)phorbol 12-(2',4'-difluorophenylacetate) 13-(4'- biphenyl)acetate; (v) 12-deoxy-6-deshydroxymethyl-6-carboxyphorbol 13-decanoate; (vi) 12-deoxy-6-deshydroxymethyl-6-carboxyphorbol 13-(2',4'- difluorophenylacetate; (vii) 6-deshydroxymethyl-6-carboxyphorbol 12-myristate 13-acetate; (viii) 6-deshydroxymethyl-6-carboxyphorbol 12-(3-phenoxy)benzoate 13- butyrate; (ix) 6-deshydroxymethyl-6-carboxyphorbol 12-(3,5-difluorophenyl)acetate 13- (3,4-difluorobenzoate); (x) 6-deshydroxymethyl-6-carboxyphorbol 12-(3,5-difluorocinnamate) 13-[3- (2',4'-difluorophenyl)propionate]; (xi) 6-deshydroxymethyl-6-carboxyphorbol 12,13-bis(2,4- dichlorophenylacetate). (xii) 6-deshydroxymethyl-6-carboxyresiniferonol 9,13,14-orthophenylacetate; (xiii) 5-trimethylsilyl-6-deshydroxymethyl-6-carboxyingenol 3,4-acetonide; (xiv) 6-deshydroxymethyl-6-carboxyphorbol 12-octyldimethylsilylacetate 13- (2',4'-difluorophenyl)acetate; and (xv) 6-deshydroxymethyl-6-carboxy-12-deoxyphorbol 13-13-(2',4'- difluorophenylacetate. EXAMPLE 53 6-Deshydroxymethyl-6-carbomethoxyphorbol 12.13-Bis(2'.4'-difluorophenylacetate) To a solution of approximately 100 mg of 6-deshydroxymethyl-6-carboxyphorbol 12,13-bis(2',4'-difluorophenylacetate) in 10 mL of tetrahydrofuran was added an excess of diazomethane in ether. After about one hour the solution was concentrated in vacuo and the residue subjected to preparative liquid chromatography [silica; hexane/ethyl acetate (70:30)] to afford 96 mg of 6-deshydroxymethyl-6- carbomethoxyphorbol 12,13-bis(2',4'-difluorophenylacetate). The structure was confirmed by NMR and mass spectra. EXAMPLE 54 In a similar manner the following compounds are prepared: (i) 6-deshydroxymethyl-6-carbomethoxyphorbol 12,13-didecanoate; and (ii) 12-deoxy-6-deshydroxymethyl-6-carbomethoxyphorbol 13-decanoate. EXAMPLE 55 6-Deshydroxymethyl-6-carbo(N-succinimidyloxy)phorbol 12.13-Bis(2'.4'- difluorophenylacetate) A solution of 580 mg of dicyclohexylcarbodiimide in 20 mL of tetrahydrofuran was added to an ice cooled mixture of 256 mg of N-hydroxysuccinimide and 138 g of 6- deshydroxymethyl-6-carboxyphorbol 12,13-bis(2',4'-difluorophenylacetate) in acetonitrile (85 mL)/tetrahydrofuran (50 mL). After 10 min the mixture was allowed to warm to room temperature under positive nitrogen pressure. After 7 hr the mixture was filtered and then concentrated in vacuo. Preparative liquid chromatography [silica; hexane/ethyl acetate (50:50)] afforded 1.53 g of 6-deshydroxymethyl-6-carbo(N- succinimidyloxy)phorbol 12,13-bis(2',4'-difluorophenylacetate), the structure of which was confirmed by NMR spectra. EXAMPLE 56 In a similar manner the following compounds are prepared: (i) 12-deoxy-6-deshydroxymethyl-6-carbo(N-succinimidyloxy)phorbol 13- decanoate; (ii) 6-deshydroxymethyl-6-carbo(N-succinimidyloxy)phorbol 12-myristate 13- acetate; and (iϋ) 6-deshydroxymethyl-6-carbo(N-succinimidyloxy)phorbol 12-(3- phenoxy)benzoate 13-butyrate. EXAMPLE 57 6-Deshydroxymethyl-6-[N-(2,3-dihydroxypropyl)carboxamido -phorbol 12,13-Bis(2',4'- difluorophenylacetate) Over 2.5 hr a total of about 50 mg of (b)-3-amino-l,2-propandiol was added to a solution of 100 mg of 6-deshydroxymethyl-6-carbo(N-succinimidyloxy)phorbol 12,13- bis(2',4'-difluorophenylacetate) in tetrahydrofuran (1 mL)/acetonitrile (0.5 mL). After another 0.75 hr the mixture was partitioned between phosphate buffer (pH 2) and ethyl acetate. The organic layer was washed with phosphate buffer (pH 8), dried over sodium sulfate and concentrated in vacuo. The resulting residue was subjected to preparative liquid chromatography [silica; methylene chloride/methanol (94:6) to afford 78 mg of 6-deshydroxymethyl-6-[N-(2,3-dihydroxypropyl)carboxamido]phorbol 12,13-bis(2',4'-difluorophenylacetate). The structure was confirmed by NMR and mass spectra. EXAMPLE 58 In a similar manner the following compounds are prepared: (i) 12-deoxy-6-deshydroxymethyl-6-[N-(2-hydroxyethyl)carboxamido]phorbol 13-decanoate; (ii) 6-deshydroxymethyl-6-[N-(2S-l-hydroxy-2-propyl)carboxamido]phorbol 12- myristate 13-acetate; (iii) 6-deshydroxymethyl-6-carbo(2-hydroxymethyl- l-piperidinyl)phorbol 12-(3- phenoxy)benzoate 13-butyrate; and (iv) 6-deshydroxymethyl-6-carboxamidophorbol 12,13-bis(2',4'- difluorophenylacetate). EXAMPLE 59 6>J)eshydroxymethyl-6-carbo(2-hydroxyethoxy)phorbol 12.13-Bis(2',4'- difluorophenylacetate) A solution consisting of 100 mg of 6-deshydroxymethyI-6-carbo(N- succinimidyloxy)phorbol 12,13-bis(2',4'-difluorophenylacetate), a few mg of 4- dimethylaminopyridine and a large excess of ethylene glycol in 1 mL of tetrahydrofuran was allowed to stand for 6 days at room temperature. The solution was then partitioned between water and ethyl acetate, the organic layer dried over sodium sulfate and concentrated in vacuo. After purification by preparative liquid chromatography [silica; hexane/ethyl acetate], 32 mg of 6-deshydroxymethyl-6-carbo(2- hydroxyethoxy)phorbol 12, 13-bis(2',4'-difluorophenylacetate) was obtained. The structure was confirmed by NMR and mass spectra. EXAMPLE 60 In a similar manner the following compounds are prepared: (i) 12-deoxy-6-deshydroxymethyl-6-carbo(2-hydroxyethyl)phorbol 13- decanoate; and (ii) 6-deshydroxymethyl-6-carbo(3-hydroxypropyl)phorbol 12-myristate 13- acetate. EXAMPLE 61 20-Deoxy-20-(3-hydroxypropylthio)phorboI 12.13-Bis(2'.4'-difluorophenyIacetate To a solution of 100 mg of 20-deoxy-20-chlorophorbol 12, 13-bis(2',4'- difluorophenylacetate) in 1 mL of acetonitrile was added a solution of 37 μL of 3- mercaptopropanol in 383 μL of 0.43 M methanolic sodium methoxide. After about 15 min the reaction mixture was partitioned between ethyl acetate and phosphate buffer (pH 8). The organic layer was dried over sodium sulfate and concentrated under a stream of nitrogen. The residue was chromatographed [silica; hexane/ethyl acetate (65:35)] to afford 77 mg of 20-deoxy-20-(3-hydroxypropylthio)phorbol 12,13-bis(2',4'- difluorophenylacetate) . EXAMPLE 62 In a similar manner the following compounds are prepared: (i) 20-deoxy-20-(2-hydroxyethylthio)phorbol 12,ϊ3-bis(2',4'- difluorophenylacetate) ; (ii<>20-deoxy-20-(2,3-dihydroxypropylthio)phorbol 12,13-bis(2',4'- difluorophenylacetate); (iii) 20-deoxy-20-(4-hydroxy-n-butylthio)phorbol 12, 13-bis(2',4'- difluorophenylacetate); (iv) 20-deoxy-20-(2-hydroxypropylthio)phorbol 12, 13-bis(2',4'- difluorophenylacetate) ; (v) 20-deoxy-20-(2-aminoethylthio)phorbol 12,13-bis(2',4'- difluorophenylacetate); (vi) 20-deoxv-20-[2-(formylamino)ethylthio]phorbol 12-myristate 13-acetate; (vii) 20-deoxy-20-[2-(acetylamino)ethylthio]phorbol 12-myristate 13-acetate; (viii) 20-deoxy-20-[2-(methylsulfonylamino)ethylthio]phorbol 12-myristate 13- acetate; (ix) 20-deoxy-20-propylthiophorbol 12, 13-bis(2',4'-difluorophenylacetate); (x) 20-deoxy-20-(2-mercaptoethyIthio)phorbol 12,13-bis(2',4'- difluorophenylacetate); (xi) 20-deoxy-20-[2-(hydroxymethyl)phenylthio]phorbol 12-myristate 13-acetate; (xii) 20-deoxy-20-(2-hydroxyethylthio)phorbol 12,13-d ibenzoate; (xiii) 20-deoxy-20-(2-hydroxyethylthio)phorbol 12, 13-diphenylacetate; (xiv) 20-deoxy-20-(2-hydroxyethylthio)phorbol 12,13- bis(pentafluorophenylacetate); (xv) 20-deoxy-20-(2-hydroxyethylthio)phorbol 12,13-bis(2,4- dichlorophenylacetate); (xvi) 20-deoxy-20-(2,3-dihydroxypropylthio)phorbol 12-[4-(9',10'- dihydrophenanthrene-2')butyrate] 13-(2',4'-difluorobenzoate); (xvii) 20-deoxy-20-(3-hydroxypropylthio)phorbol 12-(2',4'-difluorocinnamate) 13-(2',4'-difluorophenylacetate); (xviii) 20-deoxy-20-(2-hydroxyethylthio)phorbol 12-(4'-biphenylacetate) 13-[3- (3,5-difluorophenyl)propionate]; (xix) 20-deoxy-20-(2-carboxamidoethylthio)phorbol 12, 13-bis(2,4- dichlorophenylacetate); (xx) 20-deoxy-20-(2-hydroxyethylthio)phorbol 12, 13-[O,O'- bis(isopropyldimethylsilyl)]; (xxi) 20-deoxy-20-(4-hydroxy-2-butenylthio)phorbol 12, 13-bis(2',4'- difluorophenylacetate); (xxii) 12,20-dideoxy-20-(2-hydroxyethylthio)phorbol 13-(2',4'- difluorophenylacetate; (xxiii) 20-deoxy-20-(2-hydroxyethylthio)resiniferonol 9,13,14- orthophenylacetate; (xxiv) 20-deoxy-20-phenylselenophorbol 12, 13-bis(2',4'-difluorophenylacetate); and (χχ V ) 20-deoxy-20-methylselenophorbol 12,13-bis(2',4'-difluorophenylacetate) (sodium methylselenide is prepared by treatment of dimethyldiselenide with sodium borohydride). EXAMPLE 63 20-Deoxy-20-r2-t-butyldiphenylsilyloxy)ethylthiolphorbol A solution containing 12 g of 2-hydroxyethyldisulfide and 12.2 g of imidazole in 150 mL of dried N,N-dimethylformamide was treated with 41.65 g of t- butyldiphenylcholorsilane. After 2 hr, another 25 g of the silane and 5 g of imidazole were added along with 10 mL of pyridine. After another 3.5 hr the mixture was partitioned between ethyl acetate and water. The organic layer was then washed with phosphate buffer (pH 2 and pH 8, sequentially), filtered through N/N/S and concentrated in vacuo. Preparative liquid chromatography [silica; hexane/methylene chloride (90:10)] afforded about 46 g of 2-t-butyldiphenylsilyloxyethyldisulfide. To a solution of 46 g of 2-t-butyldiphenylsilyloxyethyldisulfide in 650 mL of tetrahydrofuran was added a mixture of 40 g of zinc dust and 10 mL of acetic acid in 50 mL of tetrahydrofuran. After 2 hr the supernatant was decanted into 2 L of water and the residue washed twice with 500 mL of ethyl acetate each. The aqueous solution was extracted with ethyl acetate and the combined organic layers washed with brine, filtered through N/N/S and concentrated in vacuo. The residue was dissolved in hexane/methylene chloride (85:15) and filtered through silica. Concentration in vacuo afforded 37.5 g of 2-t-butyldiphenylsilyloxyethylthiol. A solution prepared from 1 g of sodium and 17 g of 2-t-butyldiphenylsilyloxyethylthiol in 100 mL of methanol was added to approximately 4 g of crude 20-deoxy-20- chlorophorbol in 500 mL of ethyl acetate. After 35 min, a dilute phosphate buffer (pH 2) was added and then the organic layer was washed with phosphate buffer (pH 8), filtered through N/N/S and concentrated in vacuo. Preparative liquid chromatography [silica; hexane/ethyl acetate (25:75)] of the residue afforded 6.0 g of 20-deoxy-20-[2-(t- butyldiphenylsilyloxy)ethylthio]phorbol. EXAMPLE 64 20-Deoxy-20-(2-hydroxyethylthio)phorbol 12.13-Bisr3-(pentafluorophenyl propionate1 To an ice^old solution of 300 mg of l,l'-carbonyldiimidazole in 3 mL nitromethane was added 420 μL of methyl triflate followed by 441 mg of 3- (pentafluorophenyl)propionic acid in 5 mL of nitromethane. After 5 min a solution of 245 mg of 20-deoxy-20-[2-(t-butyldiphenylsiIoxy)ethylthio]phorbol and 30 mg of 4- dimethylaminopyridine in 1.5 mL of anhydrous tetrahydrofuran was added. This mixture was allowed to stand at room temperature for 17 hr then it was partitioned between ethyl acetate and phosphate buffer (pH 8). After drying (over sodium sulfate) the organic layer was concentrated in vacuo. By analysis of the thin layer chromatogram this residue was found to consist of a mixture of the mono and diesters. Thus the residue was again subjected to the above conditions for 2 hr and then treated as before. Preparative liquid chromatography [silica; hexane/ethyl acetate (85:15)] afforded 320 mg of 20-deoxy-20-[2-(t-butyldiphenylsiloxy)ethylthio]phorbol 12,13- bis[3-(pentafluorophenyl)propionate]. Three hundred μL of 1 M tetrabutylammonium fluoride in tetrahydrofuran was added to a solution of 250 mg of 20-deoxy-20-[2-(t-butyldiphenylsiloxy)ethylthio]phorbol 12,13-bis[3-(pentafluorophenyl)propionate] in 4 mL of tetrahydrofuran. After 2 hr the solution was partitioned between phosphate buffer (pH 8) and ethyl acetate. The organic layer was filtered through N/N/S and concentrated in vacuo. Preparative liquid chromatography [silica; hexane/ethyl acetate (60:40)] afforded 66 mg of 20- deoxy-20-(2-hydroxyethylthio)phorbol 12,13-bis[3-(pentafluorophenyl)propionate]. This structure was confirmed by NMR and mass spectra. EXAMPLE 65 In a similar manner the following compounds are prepared: (i) 20-deoxy-20-(2-hydroxyethylthio)phorbol 12, 13-bis(2',4'-difluorobenzoate); (ii) 20-deoxy-20-(2-hydroxyethylthio)phorbol 12,13-bis(3,4- dimethoxyphenylacetate); (iii) 20-deoxy-20-(2-hydroxyethylthio)phorbol 12,13-didecanoate (decanoyl anhydride is used as the acylating agent in the presence of pyridine and 4-dimethylaminopyridine); (iv) 20-deoxy-20-(2-hydroxyethylthio)phorbol 12,13-bis(diphenylphosphate) (diphenylchlorophosphate is used as the acylating agent in the presence of triethylamine and 4-dimethylaminopyridine); (v) 20-deoxy-20-(2-hydroxyethylthio)phorbol 12,13-bis(diethylphosphate) (diethylchlorophosphate is used as the acylating agent in the presence of triethylamine and 4-dimethylaminopyridine); and (vi) 20-deoxy-20-(2-hydroxyethylthio)phorbol 12, 13-bis[(2',4'- difluorophenyl)carbamate] (2',4'-difluorophenyl isocyanate is used as the carbamoylating agent in the presence of dibutyltin dilaurate and 4- dimethylaminopyridine). EXAMPLE 66 20-Deoxy-20-(2-carboxyethylthio)phorbol 12.13-Bis(2'.4'-difluorophenylacetate. Fifty L of 3-mercaptopropionic acid was added to 1.6 mL of 0.435 M methanolic sodium methoxide. This solution was then added to 100 mg of 20-deoxy-20- chlorophorbol 12,13-bis(2',4'-difluorophenylacetate) in 2 mL of dried acetonitrile. After 0.5 hr the mixture was partitioned between ethyl acetate and phosphate buffer (pH 2). The organic layer was then washed with phosphate buffer (pH 8), filtered through N/N/S and concentrated in vacuo. Purification by preparative liquid chromatography [silica; methylene chloride/methanol (97:3)] afforded 54 mg of 20- deoxy-20-(2-carboxyethylthio)phorbol 12,13-bis(2',4'-difluorophenylacetate). This structure was confirmed by NMR and mass spectra. EXAMPLE 67 In a similar manner the following compounds are prepared: (i) 20-deoxy-20-(2-carboxyethylthio)phorbol 12-(4'-biphenyl)acetate 13-[3-(3,5- difluorophenyl)propionate]; (ii) 20-deoxy-20-(2-carboxyethylthio)phorbol 12-myristate 13-acetate; (iii) 12,20-deoxy-20-(2-carboxyethylthio)phorbol 13-(2',4'- difluorophenylacetate; (iv) 20-deoxy-20-(2-carboxyethylthio)phorbol 12-(4'-biphenyl)acetate 13-[3-(3,5- difluorophenyl)propionate]; (v) 20-deoxy-20 " -(2-carboxyethylthio)phorbol 12-myristate 13-acetate; (vi) 12,20-dideoxy-20-(2-carboxyethylthio)phorbol 13-(2',4'- difluorophenylacetate; (vii) 20-deoxy-20-(2-carboxyethylthio)resiniferonol 9, 13, 14-orthophenylacetate; and (viii) 20-deoxy-20-[(3-hydroxylamino-3-oxo-propyl)thio]phorbol 12-myristate 13-acetate. EXAMPLE 68 20-Deoxy-20-mercaptophorbol 12.13-Bis(2'.4'-difluorophenylacetate) A solution of 72 mg of hydrated sodium hydrogensulfide in 1 mL of methanol and 2 μL of acetic acid was prepared. Two hundred and fifty μL of this solution was added to a solution of 100 mg of 20-deoxy-20-chlorophorbol 12,13-bis(2',4'- difluorophenylacetate) in 1 mL of acetonitrile. After 35 min another 100 μL of the solution was added. After 25 min phosphate buffer (pH 6) was added and the mixture was extracted with ethyl acetate. The organic layer was filtered through N/N/S and concentrated in vacuo. The residue was subjected to preparative liquid chromatography [silica; hexane/ethyl acetate mixtures] to afford 32 mg of 20-deoxy-20- mercaptophorbol 12,13-bis(2',4'-difluorophenylacetate). The structure was confirmed by NMR and mass spectra. EXAMPLE 69 In a similar manner the following compounds are prepared: (i) 20-deoxy-20-mercaptophorbol 12-(4'-biphenyl)acetate 13-[3-(3,5- difluorophenyl)propionate]; (ii) 20-deoxy-20-mercaptophorbol 12-myristate 13-acetate; (iii) 12,20-dideoxy-20-mercaptophorbol 13-(2',4'-difluorophenyl)acetate; and (iv) 20-deoxy-20-mercaptoresiniferonol 9, 13, 14-orthophenylacetate. EXAMPLE 70 20-Deoxy-20-acetonylthiophorbol 12.13-Bis(2'.4'-difluorophenylacetate) To a mixture of chloroacetone and potassium iodide in acetonitrile is added 20-deoxy- 20-mercaptophorbol 12,13-bis(2',4'-difluorophenylacetate). After a period of time the mixture is partitioned between ethyl acetate and phosphate buffer (pH 8) and the organic layer is filtered through N/N/S and concentrated in vacuo. Purification by liquid chromatography affords 20-deoxy-20-acetonylthiophorbol 12,13-bis(2',4'- difluorophenylacetate). EXAMPLE 71 20-Deoxy-20-(hydroxyethylsulfinyl)phorbol 12-Myristate 13-Acetate and 20-Deoxy-20- (hydroxyethylsulfonyl)phorbol 12-Myristate 13-Acetate To a solution of 100 mg of 20-deoxy-20-(hydroxyethylthio)phorbol 12-myristate 13- acetate in 2 mL of t-butyl alcohol was added 100 μL of 30% hydrogen peroxide. After 30 min, 2«mL of 20% aq. sodium thiosulfate was added and the mixture partitioned between water and ethyl acetate. The organic layer was dried over sodium sulfate and concentrated in vacuo. After preparative liquid chromatography [silica; methylene chloride/isopropyl alcohol] on the residue, 67 mg of 20-deoxy-20- (hydroxyethylsulfinyl)phorbol 12-myristate 13-acetate and 14 mg of 20-deoxy-20- (hydroxyethylsulfonyl)phorbol 12-myristate 13-acetate were obtained. The structures were confirmed by NMR and mass spectra. S EXAMPLE 72 In a similar manner the following compounds are prepared: (i) 20-deoxy-20-(2-hydroxyethylsulfinyl)phorbol 12, 13-bis(2',4'- difluorophenylacetate); (ii) 20-deoxy-20-(2-hydroxyethylsulfinyl)phorbol 12,13- bis(pentafluorophenylacetate); (iii) 20-deoxy-20-(propylsulfinyl)phorbol 12, 13-bis(2',4' -difluorophenylacetate); (iv) 20-deoxy-20-(2-hydroxyethylsulfinyl)phorbol 12,13-bis[3- (pentafluorophenyl)propionate]; (v) 20-deoxy-20-(2-hydroxyethylsulfinyl)-3-deoxo-3-hyroximinophorbol 12, 13- bis[3-(pentafluorophenyl)propionate]; (vi) 20-deoxy-20-(2-carboxyethylsulfinyl)phorbol 12,13-bis(2',4'- difluorophenylacetate); and (vii) 20-deoxy-20-(4-hydroxypropylsulfinyl)phorbol 12, 13-bis(2',4'- difluorophenylacetate) . EXAMPLE 73 20-Deoxy-20-(hydroxyethylsulfonyl)phorbol 12.13-Bis(2',4' -difluorophenylacetate) To a solution of 100 mg of 20-deoxy-20-(hydroxyethylthio)-phorbol 12,13-bis(2',4'- difluorophenylacetate) in 1 mL of methylene chloride was added, drop wise, 49 mg of m-chloroperbenzoic acid in 1 mL of methylene chloride. After about one hour another 28 mg of peracid was added. A few minutes later the reaction mixture was partitioned between aq. sodium thiosulfate (approximately 5%) and ethyl acetate. The organic layer was dried over sodium sulfate and concentrated in vacuo. Preparative liquid chromatography [silica; hexane/ethyl acetate (40:60)] of the residue afforded 69 mg of 20-deoxy-20-(hydroxyethylsulfonyl)phorbol 12, 13-bis(2',4'-difluorophenylacetate). The structure was confirmed by NMR and mass spectra. EXAMPLE 74 In a similar manner the following compounds are prepared: (i) 20-deoxy-20-(2-hydroxyethylsulfonyl)phorbol 12,13- bis(pentafluorophenylacetate) ; (ii) 20-deoxy-20-(propylsulfonyl)phorbol 12, 13-bis(2',4'-difluorophenylacetate); (iϋ) 20-deoxy-20-(2-hydroxyethylsulfonyl)phorbol 12,13-bis[3- (pentafluorophenyl)propionate]; (iv) 20-deoxy-20-(2-hydroxyethylsuIfonyl)-3-deoxo-3-hyroximinophorbol 12, 13- bis[3-(pentafluorophenyl)propionate]; 5 (v) 20-deoxy-20-(2-carboxyethyIsulfonyl)phorbol 12,13-bis(2',4'- difluorophenylacetate); (vi) 20-deoxy-20-(4-hydroxypropylsulfonyl)phorbol 12, 13-bis(2',4'- difluorophenylacetate); and (vii) 20-deoxy-20-(hydroxyethylsulfonyl)phorbol 12-myristate 13-acetate. 10 EXAMPLE 75 20-Deoxy-20-cyanophorbol 12-Myristate 13-Acetate 15 A mixture consisting of 500 mg of 20-deoxy-20-chlorophorbol 12-myristate 13-acetate, 80 mg of potassium cyanide, 150 mg of tetrabutylammonium chloride, 75 mg of 18- crown-6, 3 mL of chloroform and 2.8 mL of water was stirred for 22 hr at room temperature. The mixture was then partitioned between ethyl acetate and phosphate buffer (pH 8) and the organic layer was filtered through N/N/S and concentrated in 20 vacuo. Preparative liquid chromatography [silica; hexane/isopropyl alcohol (92:8)] afforded 20-deoxy-20-cyanophorbol 12-myristate 13-acetate. EXAMPLE 76 25 In a similar manner the following compounds are prepared: (i) 20-deoxy-20-cyanophorbol 12,13-diphenylacetate; (ii) 20-deoxy-20-cyanophorbol 12, 13-bis(pentafluorophenylacetate); (iii) 20-deoxy-20-cyanophorbol 12,13-bis(2,4-dichlorophenylacetate); (iv) 20-deoxy-20-cyanophorbol 12-[4-(9', 10'-dihydrophenanthrene-2')butyrate] 30 13-(2\4'-difluorobenzoate); (v) 20-deoxy-20-cyanoρhorbol 12-(2',4'-difluorocinnamate) I3-(2\4'- difluorophenylacetate); (vi) 20-deoxy-20-cyanophorbol 12-(4'-biphenyl)acetate 13-[3-(3,5- difluorophenyl)propionate]; 35 (vii) 12,20-dideoxy-20-cyanophorbol 13-(2\4'-difluorophenyl)acetate; and (viii) 20-deoxy-20-cyanoresiniferonol 9,13,14-orthophenylacetate. EXAMPLE 77 40 20-Deoxy-20-azidophorbol 12.13-Bis(2',4'-difluorophenylacetate. To a solution of 100 mg of 20-deoxy-20-chlorophorbol 12,13-bis(2\4'- difluorophenylacetate) in 1 mL of anhydrous methanol was added 88 mg of sodium azide. After 3 hr the mixture was partitioned between water and ethyl acetate. The organic layer was filtered through N/N/S and concentrated in vacuo. Upon further purification by chromatography [silica; hexane/ethyl acetate (80:20)], 88 mg of 20- deoxy-20-azidophorbol 12, 13-bis(2',4' -difluorophenylacetate) was obtained. The structure was confirmed by NMR and mass spectra. EXAMPLE 78 In a similar manner the following compounds are prepared: (i) 20-deoxy-20-azidophorbol 12,13-diphenylacetate; (ϋ) 20-deoxy-20-azidophorbol 12,13-bis(pentafluorophenylacetate); (iii) 20-deoxy-20-azidophorbol 12, 13-bis(2,4-dichlorophenylacetate); (iv) 20-deoxy-20-azidophorbol 12-[4-(9', 10'-dihydrophenanthrene-2')butyrate] 13-(2',4'-difluorobenzoate) ; (v) 20-deoxy-20-azidophorbol 12-(2',4'-difluorocinnamate) 13-(2',4'- difluorophenylacetate); (vi) 20-deoxy-20-azidophorbol 12-(4'-biphenyl)acetate 13-[3-(3,5- difluorophenyl)propionate]; (vii) 12,20-dideoxy-20-azidophorbol 13-(2',4'-difluorophenyl)acetate; (viii) 12,20-dideoxy-20-azidophorbol 13-decanoate; (ix) 20-deoxy-20-azidoresiniferonol 9,13,14-orthophenylacetate; (x) 20-deoxy-20-azidophorbol 12-myristate 13-acetate; (xi) 20-deoxy-20-azidophorbol 12,13-dibenzoate; (xii) 20-deoxy-20-azidophorbol 12-O-,13-O-bis(isopropyldimethylsilyl)ether]; (xiii) 20-deoxy-20-azidophorbol 12, 13-bis(2',4'-difluorobenzoate); (xiv) 20-deoxy-20-azidophorbol 12,13-bis(3,4-dimethoxyphenylacetate); (xv) 20-deoxy-20-azidophorbol 12,13-didecanoate; (xvi) 5-O-trimethylsilyl-20-deoxy-20-azidoingenol 3,4-acetonide; (xvii) 20-deoxy-20-azidophorbol 12-octyldimethylsilylacetate 13-(2',4'- difluorophenylacetate); and (xviii) 20-deoxy-20-azidophorbol 12-(2',4'-difluorophenylacetate) 13- diphenylphosphate. EXAMPLE 79 20-Deoxy-20-aminophorbol 12.13-Bis(2'.4'-difluorophenylacetate A solution of 47.5 mg of 20-deoxy-20-azidophorbol 12,I3-bis(2',4'- difluorophenylacetate) and 27 mg of triphenylphosphine in 1 mL of tetrahydrofuran was stirred for 4.5 hr at room temperature. At this time 10 mg of triphenylphosphine was added followed 1.5 hr later by lOO L of water and 1.5 hr after that with a few mg of silica. After another 1.5 hr the mixture was filtered through silica gel and concentrated by a stream of nitrogen. Preparative liquid chromatography afforded 18 mg of 20-deoxy-20-aminophorbol 12,13-bis(2',4'-difluorophenylacetate). EXAMPLE 80 In a similar manner the following compounds are prepared: (i) 20-deoxy-20-aminophorbol 12,13-diphenylacetate; (ϋ) 20-deoxy-20-aminophorbol 12,13-bis(pentafluorophenylacetate); (iii) 20-deoxy-20-aminophorbol 12, 13-bis(2,4-dichlorophenylacetate); (iv) 20-deoxy-20-aminophorbol 12-[4-(9', 10'-dihydrophenanthrene-2')butyrate] 13-(2',4'-difluorobenzoate); (v) 20-deoxy-20-aminophorbol 12-(4'-biphenyl)acetate 13-[3-(3,5- difluorophenyl)propionate]; (vi) 12,20-dideoxy-20-aminophorbol 13-(2',4'-difl uorophenyl)acetate; (vii) 20-deoxy-20-aminoresiniferonol 9, 13, 14-orthophenylacetate; (viii) 20-deoxy-20-aminophorbol 12-myristate 13-acetate; (ix) 20-deoxy-20-aminophorbol 12,13-dibenzoate; (x) 20-deoxy-20-aminophorbol 12,13-bis(2',4'-difluorobenzoate); and (xi) 20-deoxy-20-aminophorbol 12,13-bis(3,4-dimethoxyphenylacetate). EXAMPLE 81 20-Deoxy-20-(N'-methylureido)phorbol 12.13-Bis(2'.4'-difluorophenylacetate) To a solution of 50 mg of 20-deoxy-20-aminophorbol 12,13-bis(2',4'- difluorophenylacetate) in 1 mL of tetrahydrofuran is added 20 μL of methyl isocyanate. After several hours some methanol is added to the reaction mixture to consume excess isocyanate and the mixture is concentrated. Purification by liquid chromatography affords 20-deoxy-20-(N'-ureido)phorbol 12, 13-bis(2',4'-difluorophenylacetate). EXAMPLE 82 In a similar manner the following compounds are prepared: (i) 20-deoxy-20-(N'-ethylureido)phorbol 12-myristate 13-acetate; (ii) 20-deoxy-20-(N'-propylureido)phorbol 12,13-dibenzoate; (iii) 20-deoxy-20-(N'-methylthioureido)phorbol 12,13-bis(2',4'- difluorobenzoate); (iv) 12,20-dideoxy-20-(N'-butylureido)phorbol 13-(2',4'-difluorophenyl)acetate; (v) 20-deoxy-20-[N'-(3-methoxyphenyl)ureido]phorbol 12, 13-bis(2',4'- difluorophenylacetate); (vi) 20-deoxy-20-[N'-(3-trifluoromethylphenyl)ureido]phorbol 12, 13-bis(2',4'- difluorophenylacetate); (vii) 20-deoxy-20-(N'-allylthioureido)phorbol 12,13-bis(2',4'- difluorophenylacetate) ; (viii) 20-deoxy-20-(N'-phenethylthioureido)phorbol 12, 13-bis(2',4'- difluorophenylacetate); and (ix) 20-deoxy-20-(N'-methylureido)resiniferonol 9,13,14-orthophenylacetate. EXAMPLE 83 20-Deoxy-20-bromophorbol 12.13-Bis(2 , ,4'-difluorophenylacetate) To a solution of 1.0 g of phorbol 12,13-bis(2',4'-difluorophenylacetate) and 1.58 g of 2,6-lutidine in 20 mL of dry acetonitrile was added 3.21 g of dibromotriphenylphosphorane. After 0.5 hr approximately 10 mL of water was added and the mixture was extracted with ethyl acetate. The combined organic layers were washed with phosphate buffers, pH 2 and pH 8 sequentially, and then brine before being filtered through N/N/S and concentrated in vacuo. Preparative liquid chromatography [silica; hexane/ethyl acetate (75:25)] afforded 665 mg of 20-deoxy-20- bromophorbol 12,13-bis(2',4'-difluorophenylacetate). The structure was confirmed by NMR and mass spectra. EXAMPLE 84 In a similar manner the following compounds are prepared: (i)..20-desoxy-20-bromophorbol 12-myristate 13-acetate; (ϋ) 20-desoxy-20-bromophorbol 12-(4-biphenyl)acetate 13-acetate; and (iii) 20-desoxy-20-bromophorbol 12-[(2,2-dimethyl)(2',4'-difluorophenyl)acetate 13-butyrate. EXAMPLE 85 SUBSTITUTE SHEET 20-Deoxy-20-rN.N-bis(2-hydroxyethyl)aminolphorbol 12.13-Bis(2'.4'- • difluorophenylacetate) 5 To a solution of 100 mg of 20-deoxy-20-bromophorbol 12, 13-bis(2',4'- difluorophenylacetate) and 11 μL of pyridine in 1 mL of acetonitrile was added, over a 5 hr period, 50 mg of diethanolamine in 1 mL of acetonitrile. The reaction was then partitioned between ethyl acetate and phosphate buffer (pH 2). The organic layer was washed with phosphate buffer (pH 8), dried over sodium sulfate and concentrated in 10 vacuo. After preparative liquid chromatography [silica; methylene chloride/tetrahydrofuran (75:25)], 51 mg of 20-deoxy-20-[N,N-bis(2- hydroxyethyl)amino]phorbol 12,13-bis(2',4'-difluorophenylacetate) was obtained. The structure was confirmed by NMR and mass spectra. 15 EXAMPLE 86 In a similar manner the following compounds are prepared: (i) 20-deoxy-20-(2-hydroxyethylamino)phorbol 12,13-bis(2',4'- difluorophenylacetate); 20 (ϋ) 20-desoxy-20-[(2S-l-hydroxy-2-propyl)amino]phorbol 12-myristate 13- acetate; (iii) 20-desoxy-20-(2-hydroxymethyl-l-piperidinyl)phorbol 12-(4- biphenyl)acetate 13-acetate; and (iv) 20-desoxy-20-[(2-carboxyethyl)amino]phorbol 12-[(2,2-dimethyl)(2',4'- 25 difluorophenylacetate 13-butyrate. EXAMPLE 87 20-Deoxy-20-(l-imidazolyl)phorbol 12.13-Bis(2'.4'-difluorophenylacetate) and 20- 30 Deoxy-20-(2-imidazolyl)phorbol 12,13-Bis(2'.4'-difluorophenvIacetate) Twelve mg of imidazole was added to 100 mg of 20-deoxy-20-bromophorbol 12,13- bis(2',4'-difluorophenylacetate) in 1.5 mL of acetonitrile followed by 11 μL of pyridine 10 min later. After 2 hr another 10 mg of imidazole was added. Three hr later a drop 35 of pyrollidinyl pyridine was added. After 1.5 hr the mixture was partitioned between ethyl acetate and phosphate buffer (pH 2). The organic layer was washed with phosphate buffer (pH 8), dried over sodium sulfate and concentrated in vacuo. The residue was chromatographed [silica; methylene chloride/tetrahydrofuran (65:35)] to afford 33 mg of 20-deoxy-20-(l-imidazolyl)phorbol 12,13-bis(2',4'- 40 difluorophenylacetate) and 13 mg of 20-deoxy-20-(2-imidazolyl)phorboI 12,13-bis(2',4'- difluorophenylacetate). The structures were confirmed by NMR and mass spectra. EXAMPLE 88 20-Deoxy-20-(4-dimethylaminopyridinium- l-yl)phorbol 12-Myristate 13-Acetate. Bromide (Iodide) salt A solution of 75 mg of 20-deoxy-20-bromophorbol 12-myristate 13-acetate and 1 mL of ethylene glycol in 1 mL of acetone was treated with 15 mg of potassium iodide and 30 mg of 4-dimethylaminopyridine at room temperature. After 30 min the mixture was partitioned between ethyl acetate and phosphate buffer (pH 2). The organic layer was washed with phosphate buffer (pH 8), dried over sodium sulfate and concentrated in vacuo. After purification by preparative liquid chromatography [silica; methylene chloride/methanol (50:50)] 20-deoxy-20-(4-dimethylaminopyridinium-l-yl)phorbol 12- myristate 13-acetate, bromide (iodide) salt, was obtained. It did not crystallize. EXAMPLE 89 20-Deoxy-20-r(3-hydroxymethylphenyl)aminophorbol 12.13-Bis(2'.4'- difluorophenylacetate) A total of 99 mg of 3-aminobenzyl alcohol was added over 1.5 hr to 95 mg of 20-deoxy- 20-oxophorbol 12,13-bis(2',4'-difluorophenylacetate) in 3 mL of acetonitrile/10% aq. acetic acid (9:1). To this mixture was then added 23 mg of sodium cyanoborohydride, and, after 25 min, phosphate buffer (pH 2) was added. This solution was extracted with ethyl acetate and the organic layer washed with phosphate buffer (pH 8), filtered through N/N/S and concentrated in vacuo. Chromatographic purification [silica; hexane/ethyl acetate (55:45)] afforded 70 mg of 20-deoxy-20-[(3- hydroxymethylphenyl)amino]phorbol 12,13-bis(2',4'-difluorophenylacetate). The structure was confirmed by NMR and mass spectra. EXAMPLE 90 In a similar manner the following compounds are prepared: (i) 20-deoxy-20-[(4-(2-hydroxyethyl)phenyl)amino]phorbol 12, 13-didecanoate; (ii) 20-deoxy-20-[(3-caι-bomethoxymethylphenyl)amino]phorbol 12-myristate 13-acetate; (iii) 20-deoxy-20-[(3-cyanophenyl)amino]phorbol 12-(3-phenoxy)benzoate 13- butyrate; (iv) 20-deoxy-20-[(4-carboxamidophenyl)amino]phorbol 12-(3,5- difluorophenyl)acetate 13-(3,4-difluorobenzoate); (v) 20-deoxy-20-[(3-acetylphenyl)amino]phorbol 12,13-bis(2,4- dichlorophenylacetate); (vi) 20-deoxy-20-[(3-dihydroxyboranylphenyl)amino]phorbol 12,13-bis(2',4'- difluorophenylacetate); (vii) 20-deoxy-20-[(4-oxoarsinylphenyl)amino]phorbol 12, 13-bis(2',4'- difluorophenylacetate); (viii) 20-deoxy-20-[(4-dihydroxyphosphonylphenyl)amino]phorbol 12,13- bis(2',4'-difluorophenylacetate); and (ix) 12,20-dideoxy-20-[(3-hydroxymethylphenyl)amino]phorbol 13-(2',4'- difluorophenyl)acetate. EXAMPLE 91 20-O-(2-Hydroxyethyl)phorbol 12-Myristate 13-Acetate A solution of 75 mg of 20-deoxy-20-bromophorbol 12-myristate 13-acetate and 1 mL of ethylene glycol in 1 mL of acetone was treated with 15 mg of potassium iodide and 30 mg of 2,6-di-t-butyl-4-methylpyridine at room temperature in the dark and under a nitrogen atmosphere for 12 days. It was then partitioned between ethyl acetate and phosphate buffer (pH 2). The organic layer was washed with phosphate buffer (pH 8), filtered through N/N/S and concentrated in vacuo. After purification by preparative liquid chromatography [silica; hexane/ethyl acetate (50:50)] 28.5 mg of 20-O-(2- hydroxyethyl)phorboI 12-myristate 13-acetate was obtained. The structure was confirmed by NMR and high resolution mass spectra. EXAMPLE 92 In a similar manner the following compounds are prepared: (i) 20-O-(4-hydroxy-2-butynyl)phorbol 12,13 bis(2',4'-difluorophenylacetate); (ii) 20-O-(4-hydroxy-2-butenyl)phorbol 12-(4'-biphenyl)acetate 13-acetate; (iii) 20-O-acetonylphorbol 12-[(2,2-dimethyl)(2',4'-difluorophenyl)acetate 13- butyrate; (iv) 20-O-(2-propyl)phorbol 12-myristate 13-acetate; and (v) 20-O-(3-hydroxypropyl)phorbol 12-myristate 13-acetate. EXAMPLE 93 20-O-(4-Hydroxyphenoxy)carbonylphorboI 12.13-Bis(2 , ,4'-difluorophenylacetate) To a solution of 8.26 g of hydroquinone and 6.3 g of imidazole in 80 mL of pyridine was added 20.6 g of t-butyldiphenylcholorosilane in 20 mL of pyridine. After 1.5 hr the mixture was partitioned between water and ethyl acetate. The organic layer was washed twice with phosphate buffer (pH 2) and once each with phosphate buffer (pH 8) and brine before being filtered through N/N/S and concentrated in vacuo. Preparative liquid chromatography [silica; hexane/ethyl acetate (85:15)] afforded 14.4 g of 4-(t-butyldiphenylsilyloxy)phenol. The structure was confirmed by its NMR spectrum. To a solution of 46 mg of l, -carbonyldiimidazole in 0.5 mL nitromethane was added 65 μL of methyl triflate followed by 100 mg of 4-(t-butyldiphenylsilyloxy)phenol in 1.4 mL of nitromethane. A total of 1.9 mL of this solution was added to a mixture of 100 mg of phorbol 12,13-bis(2',4'-difluorophenylacetate) and approximately 10 mg of 4- dimethylaminopyridine in 500 μL of anhydrous tetrahydrofuran. After 4.5 hr this mixture was partitioned between ethyl acetate and water. The organic layer was filtered through N/N/S, concentrated in vacuo and subjected to preparative liquid chromatography [silica; hexane/ethyl acetate (80:20)] to afford 142 mg of 20-O-[4-(t- butyidiphenylsilyloxy)phenoxy]carbonylphorbol 12,13-bis(2',4'-difluorophenylacetate). A solution of this material in 1 mL tetrahydrofuran was treated with 160 μL of 1.0 M tetrabutylammonium fluoride in tetrahydrofuran. After 14 min the mixture was partitioned between ethyl acetate and phosphate buffer (pH 8). The organic layer was filtered through N/N/S and concentrated in vacuo. After preparative liquid chromatography [silica; hexane/ethyl acetate (65:35)] 108 mg of 20-O-(4- hydroxyphenoxy)carbonylphorbol 12,13-bis(2',4'-difluorophenylacetate) was obtained. The structure was confirmed by NMR and mass spectra. EXAMPLE 94 In a similar manner the following compounds are prepared: (i) 20-O-(4-hydroxyphenoxy)carbonylphorbol 12,13-didecanoate; (ii ' ), 20-O-(4-hydroxyphenoxy)carbonyl-12-deoxyphorbol 13-decanoate; (iii) 20-O-(4-hydroxyphenoxy)carbonyl-12-deoxyphorbol 13-(2',4'- difluorophenyl)acetate; (iv) 20-O-(3-hydroxyphenoxy)carbonylphorbol 12-myristate 13-acetate; (v) 20-O-(3-hydroxyphenoxy)carbonylphorbol 12-(3-phenoxy)benzoate 13- butyrate; (vi) 20-O-(4-hydroxyphenoxy)carbonylphorbol 12-(3,5-difluorophenyl)acetate 13-(3,4-difluorobenzoate); (vii) 20-O-(2-hydroxyphenoxy)carbonylphorboI 12-(3,5-difluorocinnamate) 13- [3-(2\4'-difluorophenyl)propionate]; (viii) 20-O-phenoxycarbonylphorbol 12,13-bis(2,4-dichlorophenylacetate); (ix) 20-O-(2-hydroxyphenoxy)carbonylingenol 3-benzoate; (x) 20-O-(3-hydroxyphenoxy)carbonylresiniferonol 9, 13, 14-orthophenylacetate; (xi) 3-[(4-hydroxy)phenoxycarbonyloxymethyl]- 1 ,6-dioxo-2,5- dioxacyclotetracosane; (xii) 30-O-(4-hydroxyphenoxy)carbonyldebromoaplysiatoxin 20-acetate; and (xiii) 26-O-(4-hydroxyphenoxy)carbonylbryostatin 1. EXAMPLE 95 Phorbol 12-Myristate 13-Acetate 20-(4'-Fluoro-3'-nitrophenyl)carbamate To a solution of 100 mg of phorbol 12-myristate 13-acetate in 1 mL of tetrahydrofuran was added, 73 mg of 4-fluoro-3-nitrophenyl isocyanate, 5 mg of dibutyltin dilaurate and 25 mg of 4-dimethylaminopyridine. After 3 hr 100 L of methanol was added to the reaction mixture. After removal of the solvents under a nitrogen stream, the mixture was subjected to preparative liquid chromatography [silica; hexane/iso-propyl alcohol (86:14) to afford 71 mg of phorbol 12-myristate 13-acetate 20-(4'-fluoro-3'- nitrophenyl)carbamate. EXAMPLE 96 In a similar manner the following compounds are prepared: (i) phorbol 12-myristate 13-acetate 20-ethylcarbamate; (ii) phorbol 12-myristate 13-acetate 20-n-propylcarbamate; (fii) phorbol 12-myristate 13-acetate 20-n-butylcarbamate; (iv) phorbol 1 ,13-didecanoate 20-(3-trifluoromethyl)phenylcarbamate; (v) phorbol 12,13-bis(2\4'-difluorophenylacetate) 20-methylcarbamate; (vi) 12-deoxyphorbol 13-decanoate 20-(3-methoxy)phenylcarbamate; (vii) 12-deoxyphorbol 13-(2',4'-difluorophenyl)acetate 20-n-propylcarbamate; (viii) phorbol 12-(3-phenoxy)benzoate 13-butyrate 20-(4- carboethoxy)phenylcarbamate; (ix) phorbol 12-(3,5-difluorophenyl)acetate 13-(3,4-difluorobenzoate) 20- carboethoxymethylcarbamate; (x) ingenol 3-benzoate 20-methylcarbamate; (xi) resiniferonol 9,13,14-orthophenylacetate 20-ethylcarbamate; (xii) mezerein 20-methylcarbamate; (xiii) 3-[(N-methylamino)carbonyloxymethyl]- l,6-dioxo-2,5- dioxacyclotetracosane; (xiv) debromoaplysiatoxin 20-acetate 30-methylcarbamate; and (xv) bryostatin 1 26-methylcarbamate. EXAMPLE 97 Phorbol 12-Myristate 13-Acetate 20-Methylthiocarbamate To a solution of 100 mg of phorbol 12-myristate 13-acetate in 1 mL of tetrahydrofuran was added, over a six hour period, a total of 180 mg of methyl isothiocyanate, 105 mg of dibutyltin dilaurate and 125 mg of 4-dimethylaminopyridine. After 4 days the reaction mixture was subjected to preparative liquid chromatography [silica; hexane/ethyl acetate mixtures] to afford 4 mg of phorbol 12-myristate 13-acetate 20- methylthiocarbamate. EXAMPLE 98 In a similar manner the following compounds are prepared: (i) phorbol 12,13-didecanoate 20-allylthiocarbamate; (ii) phorbol 12,13-bis(2',4'-difluorophenylacetate) 20-2- tetrahydrofuranylmethylthiocarbamate; (fii) 12-deoxyphorbol 13-(2',4'-difluorophenyl)acetate 20-(3- methoxypropyl)thiocarbamate; and (iv) phorbol 12-(3-phenoxy)benzoate 13-butyrate 20-phenethylthiocarbamate. EXAMPLE 99 Phorbol 12-Myristate 13-Acetate 20-Carbamate To a solution of 100 mg of phorbol 12-myristate 13-acetate in 2 mL of methylene chloride was added 25 mg of chlorosulfonyl isocyanate in 200 μL of methylene chloride. After 3 hr a few hundred μL of phosphate buffer (pH 2) was added. After 20 min pH 8 buffer was added and the mixture extracted with ethyl acetate. The organic layer was filtered through N/N/S and concentrated in vacuo. After preparative liquid chromatography [silica; hexane/tetrahydrofuran (65/35)], 57 mg of phorbol 12- myristate 13-acetate 20-carbamate was obtained. SUBSTITUTE SHEET EXAMPLE 100 In a similar manner the following compounds are prepared: 5 (i) phorbol 12,13-bis(2',4'-difluorophenylacetate) 20-carbamate; (ii) phorbol 12,13-didecanoate 20-carbamate; (iii) phorbol 12-(3-phenoxy)benzoate 13-butyrate 20-carbamate; and (iv) 12-deoxyphorbol 13-(2',4'-difluorophenyl)acetate 20-carbamate. 10 EXAMPLE 101 20-Deoxy-20-(2-hydroxyethylsulfonyl)-3-deoxo-3-hydroximinophorbol 12.13-Bis(2',4'- difluorophenylacetate) 15 To a solution of 100 mg of 20-deoxy-20-(2-hydroxyethylthio)phorbol 12,13-bis(2',4'- difluorophenylacetate) in 1 mL of pyridine was added 214 mg of hydroxylamine hydrochloride. After heating at 53°C for 8 hr the mixture was cooled and partitioned between phosphate buffer (pH 2) and ethyl acetate. The organic layer was washed with phosphate buffer (pH 8), dried over sodium sulfate and concentrated in vacuo. 20 Preparative liquid chromatography of the residue [silica; methylene chloride/tetrahydrofuran (92.5:7.5)] afforded 62 mg of 20-deoxy-20-(2- hydroxyethylsulfonyl)-3-deoxo-3-hydroximinophorbol 12,13-bis(2',4'- difluorophenylacetate). The structure was confirmed by NMR and mass spectra. 25 EXAMPLE 102 In a similar manner the following compounds are prepared: (i) 6-deshydroxymethyl-6-carboxy-3-deoxo-3-hydroximinophorbol 12,13- bis(2',4'-difluorophenylacetate); and 30 (ϋ) 20-deoxy-20-(2-hydroxyethylthio)-3-deoxo-3-hydroximinophorbol 12,13- bis(pentafluorophenylpropionate). EXAMPLE 103 35 20-Deoxy-20-(2-hvdroxyethylthio)-3-deoxo-3-beta-hvdroχyphorbol 12.13-Bis(2'.4'- difluorophenylacetate) To a mixture of 25 mg of 20-deoxy-20-(2-hydroxyethylthio)phorboI 12,13-bis(2',4'- difluorophenylacetate) and 15 mg of cerium (III) chloride in 0.5 mL of methanol was 40 added approximately 3 mg of sodium borohydride. After 8 min the mixture was partitioned between phosphate buffer (pH 2) and ethyl acetate. The organic layer was washed with phosphate buffer (pH 8), dried over sodium sulfate and concentrated by a stream of nitrogen. Purification by preparative liquid chromatography [silica; 5 hexane/ethyl acetate (50:50)] afforded 13 mg of 20-deoxy-20-(2-hydroxyethylthio)-3- deoxo-3-beta-hydroxyphorbol 12,13-bis(2',4'-difluorophenylacetate). The structure was confirmed by NMR and high resolution mass spectra. EXAMPLE 104 10 In a similar manner the following compounds are prepared: (i) 3-deoxo-3-beta-hydroxyphorboI 12-[4-(9', lO'-dihydrophenanthren- 2')butyrate]; and (ii) 20-deoxy-20-carboxy-3-deoxo-3-beta-hydroxyphorbol 12, 13-bis(2',4'- 15 difluorophenylacetate). EXAMPLE 105 20-Deoxyphorbol 12-Myristate 13-Acetate and 12-beta-MyristoyIoxy- 13-acetoxy-4.9- 20 dihvdroxy-1.6(20)-tigladien-3-one and 20-Deoxy-20-r20'-deoxyphorbol-20'-yl (12'- myristate 13'-acetate lphorbol 12-Myristate 13-Acetate Extensive further purification of the crude residue from Example 15 by preparative liquid chromatography afforded 20-deoxyphorbol 12-myristate 13-acetate, 12-beta- 25 myristoyloxy-13-acetoxy-4,9-dihydroxy-l,6(20)-tigladien-3-one and 20-deoxy-20-[20'- deoxyphorbol-20'-yl (12'-myristate 13'-acetate)]phorbol 12-myristate 13-acetate. These structures were confirmed by NMR and high resolution mass spectra. EXAMPLE 106 30 6-Dehydroxymethyl-6-(2'-methoxycarbonyl-(E)-vinyl)phorbol 12-Myristate 13-Acetate A solution of 100 mg of 20-deoxy-20-oxophorbol 12-myristate 13-acetate and 90 mg of methyl triphenylphosphoranylideneacetate in 4 mL of toluene was allowed to stir for 35 18 hours at room temperature. After concentration in vacuo, the residue was purified by preparative liquid chromatography [silica; methylene chloride/tetrahydrofuran (96:4)] to yield 116 mg of 6-dehydroxymethyl-6-(2'-methoxycarbonyl-(E)-vinyl)phorbol 12-myristate 13-acetate as an oil. 40 EXAMPLE 107 20-Deoxyphorbol 12-Myristate 13-Acetate 20-sulfonic Acid, Triethylamine Salt A mixture containing 100 mg of 20-deoxy-20-chlorophorbol 12-myristate 13-acetate, 22 mg of sodium sulfite, 20 mg of sodium iodide and 0.6 mmoles of acetic acid in about 11 mL of ethanol/water (approximately 1:1) was stirred for a total of 4 hours alternating between ambient and 60IC. After that time the mixture was concentrated in vacuo and partitioned between ethyl acetate and brine to afford a residue which was purified by liquid chromatography [silica; methylene chloride/methanol (90:10)] to yield 82 mg of 20-deoxyphorbol-20-sulfonic acid 12-myristate 13-acetate. This acid was converted to its triethylamine salt by the addition of 24 μL of triethylamine in t-butyl methyl ether followed by concentration in vacuo. 20-Deoxy-20-trimethylsilylphorbol 12,13-Bis(2',4'-difluorophenylacetate EXAMPLE 108 20-Deoxy-20-trimethylphosphoniumphorbol 12.13-Bis(2'.4'-difluorophenylacetate Bromide To solution of approximately 50 mg of 20-deoxy-20-bromophorbol 12,13-bis(2',4'- difluorophenylacetate) in 1 mL of dry acetonitrile is added 100 μL of 1M trimethylphosphine in toluene. After a period of time this mixture is concentrated under a nitrogen stream and the residue is subjected to chromatographic purification to afford 20-deoxy-20-trimethylphosphoniumphorbol 12,13-bis(2',4'- difluorophenylacetate bromide. EXAMPLE 109 Demonstration of Anti-HIV Activity of20-Deoxy-20-chlorophorbol 12.13-bis(2',4'- difluorophenylacetate) Human peripheral blood lymphocytes were isolated from the buffy coat fractions of blood donations. The lymphocytes were then stimulated with 5 micrograms/ml of phytohemagglutinin for 48 hours. Prior to infection with HIV, the lymphocytes were washed and resuspended in mitogen-free medium. On day 0 the cells were infected with HIV and were cultured for four days in the presence or absence of graded concentrations of 20-deoxy-20-chlorophorbol 12,13-bis(2',4'-difluorophenylacetate. On days 3 and 4 the supernatant levels of total viral RNA and viral core protein p24 were determined at each drug concentration and dose-response curves were used to determine the concentration of drug giving 50% inhibition of production of viral RNA and of p24 core protein. At four days these EDgø values were less than 100 pmolar for both RNA and p24. EXAMPLE 110 In similar manner the anti-HIV ED50 values for RNA [drug concentration is in brackets] for the following compounds were determined from dose-response curves or by estimation from one or more experimental drug concentrations: (i) 14-deoxy- 14-(2'-hydroxyethylthio)-7-octyl-[9S,12S]-indolactam V [l μ molar]; (ii) 20-deoxy-20-bromophorbol 12,13-bis(2',4'-difluorophenylacetate) [less than 1 nmolar]; (iii) 20-deoxy-20-chlorophorbol 12,13-bis(pentafluorophenylacetate) [less than 1 nmolar]; (iv) 20-deoxy-20-cyanophorbol 12-myristate 13-acetate [l.δ μmolar]; (v) phorbol 12-myristate 13-acetate 20-(4'-fluoro-3'-nitrophenyl)carbamate [4 μmolar]; (vi) 20-deoxy-20-(2-hydroxyethylthio)phorbol 12,13-bis(2',4'- difluorophenylacetate) [1.0 μmolar]; (vii) 20-deoxy-20-(2,3-dihydroxypropylthio)phorbol 12, 13-bis(2',4'- difluorophenylacetate) [3 μmolar]; (viii) 20-deoxy-20-hydroximinophorbol 12, 13-bis(2',4' -difluorophenylacetate) [5.5 μmolar]; (ix) 20-deoxy-3-deoxo-3,20-bis(hydroximino)phorboI 12,13-bis(2',4'- difluorophenylacetate) [45 nmolar]; (x) 6-deshydroxymethyl-6-carboxyphorbol 12, 13-bis(2',4' -difluorophenylacetate) [less than 1 nmolar]; (xi) 6-deshydroxymethyl-6-carbomethoxyphorbol 12,13-bis(2',4'- difluorophenylacetate) [ 1.6 μmolar]; (xϋ) 20-deoxy-20-(2-carboxyethylthio)phorbol 12,13-bis(2',4'- difluorophenylacetate) [4.5 μmolar]; (xiii) 20-deoxy-20-(2-hydroxyethylsulfinyl)phorbol 12, 13-bis(2',4'- difluorophenylacetate) [ 1.6 μmolar]; (xiv) 20-deoxy-20-(hydroxyethylsulfonyl)phorbol 12,13-bis(2',4'- difluorophenylacetate) [5.0 μmolar]; (xv) 20-deoxy-20-(hydroxyethylsulfinyl)phorbol 12-myristate 13-acetate [1.1 μ molar]; (xvi) 20-deoxy-20-(hydroxyethylsulfonyl)phorbol 12-myristate 13-acetate [500 nmolar]; (xvii) 20-deoxy-20-[(3-hydroxymethylphenyl)amino]phorbol 12,13-bis(2',4'- difluorophenylacetate) [180 nmolar]; (xviii) 20-deoxy-20-azidophorbol I2,13-bis(2',4'-difluorophenylacetate) [65 nmolar]; (xix) 20-deoxy-20-aminophorbol 12,13-bis(2',4'-difluorophenylacetate) [100 nmolar]; (xx) 20-O-(4-hydroxyphenoxy)carbonylphorbol 12,13-bis(2',4'- difluorophenylacetate) [less than 10 nmolar]; (xxi) 20-deoxy-20-propylthiophorbol 12,13-bis(2',4'-difluorophenylacetate) [10 nmolar]; (xxii) 20-deoxy-20-propylsulfinylphorbol 12,13-bis(2',4'-difluorophenylacetate) [500 nmolar]; (xxiii) 20-deoxy-20-(2-mercaptoethylthio)phorbol 12, 13-bis(2',4'- difluorophenylacetate) [50 nmolar]; (xxiv) 2-deshydroxymethyl-6-cyanophorbol 12,13-bis(2',4'- difluorophenylacetate) [less than 100 nmolar]; (xxv) 14-deoxy- 14-(2-hydroxyethylthio)indolactam V [1 μmolar]; (xxvi) 14-deoxy- 14-(2-hydroxyethylthio)-7-octylindolactam V [100 nmolar]; and (xxvii) 3-[(2'-hydroxyethylthio)methyl]-l,6-dioxo-2,5-dioxacyclotetracosane [10 nmolar]. (This space was intentionally left blank . ) SUBSTITUTE SHEET

Claims: CLAIMS 1. A compound, in the form of an individual isomer, an isomer mixture, a racemate or optical antipode, or a pharmaceutically acceptable salt thereof, of the formula: 10 P - G wherein P represents a radical, formally derived from a parent compound, which compound: 15 a. binds reversibly or irreversibly to a diacylglycerol-type receptor; and/or b. activates any form of the enzyme protein kinase C; and c contains an hydroxymethyl or 1-hydroxyethyl group bonded to a carbon atom; and 20 wherein G is any group of 55 or fewer atoms selected from carbon, hydrogen, oxygen, nitrogen, halogen, sulfur, phosphorus, silicon, arsenic, boron and selenium either i) singly or doubly bonded to the carbon atom of the parent compound in place of the hydroxymethyl or 1-hydroxyethyl group; or ii) singly or doubly bonded to a carbon atom immediately adjacent to the carbon atom to 25 which the hydroxymethyl or 1-hydroxyethyl group is bound in the parent compound; and wherein the hydroxymethyl or 1-hydroxyethyl group of the parent compound is absent or has been replaced by G. 30 2. A compound, in the form of an individual isomer, an isomer mixture, a racemate or optical antipode, or a pharmaceutically acceptable salt thereof, of the formula: p o _ S o " E o 35 wherein P 0 represents a radical, formally derived from a parent compound, which compound: a. binds reversibly or irreversibly to a diacylglycerol-type receptor; and/or b. activates any form of the enzyme protein kinase C; and 40 c. contains an hydroxymethyl or 1-hydroxy-ethyl group bonded to a carbon atom; and wherein S Q -E 0 represents a moiety which is either i) singly or doubly bonded to the carbon atom of the parent compound in place of the hydroxymethyl or 1- hydroxyethyl group; or ii) singly or doubly bonded to a carbon atom immediately adjacent to the carbon atom to which the hydroxymethyl or 1- hydroxyethyl group is bound in the parent compound; and wherein S Q is a substituted or unsubstituted, saturated, unsaturated and/or aromatic, straight or branched, acyclic, ring-containing and/or ring-carrying chain of atoms which separates P Q and E Q by a linear count of at least two but not more than 12 atoms and contains and/or carries not more than 9 heteroatoms selected from oxygen, nitrogen, silicon, sulfur, phosphorus, arsenic, boron and selenium, and not more than 16 halogen atoms; provided that the total number of atoms does not exceed 35; and wherein E Q comprises hydrogen, halogen or a saturated or singly or multiply unsaturated group containing up to 15 carbon atoms and optionally containing 1 to 12 halogen atoms and/or 1 to 6 heteroatoms selected from oxygen, nitrogen, silicon, sulfur, phosphorus, arsenic.boron and selenium, or wherein S 0 E 0 taken together may be a hydrogen, halogen, thionic sulfur atom or ketonic oxygen atom or a hydroxy, amine, or thiol group singly or doubly bonded to the carbon atom of the parent compound P Q in place of the hydroxymethyl or 1-hydroxyethyl group. 3. A compound of the formula: Pχ " Sχ wherein P χ is selected from the group consisting of P j , P2, P3, P4, P5, and Pg; wherein P j is a radical of the formula: SUBSTITUTE SHEET in the form of an individual isomer, an isomer mixture, a racemate or optical antipode, or a pharmaceutically acceptable salt thereof; wherein A- and A^ may be independently selected from hydrogen, halogen and a substituent having not more than 34 carbon atoms, not more than 24 halogen atoms and not more than 9 heteroatoms selected from oxygen, nitrogen, silicon, phosphorus and sulfur; or A 1 and A-" taken together may complete a 5- or 6-membered saturated or unsaturated carbocyclic or heterocyclic ring, optionally substituted by 1-8 halogens and/or other groups, which halogens and groups taken together contain a total of not more than 30 carbon atoms, not more than 24 halogen atoms and not more than 9 heteroatoms selected from oxygen, nitrogen, silicon, phosphorus and sulfur; A=? is a three atom chain which carries S χ Eχ and completes a 7-membered saturated or unsaturated carbocyclic ring optionally substituted by 1-6 halogens and/or other groups, which halogens and groups taken together, excluding S χ Eχ, contain not more than 12 carbon atoms, not more than 8 halogen atoms, and not more than 5 heteroatoms selected from oxygen, nitrogen, silicon, phosphorus and sulfur; provided that, including S χ E , the middle carbon atom of A 3 is not substituted by hydroxymethyl or 1-hydroxyethyl; A 4 completes a 6- or 7-membered carbocyclic or heterocyclic ring which is connected in the ? configuration to either carbon atom 9 or 10 and carries an 5 11-methyl group in the a or β configuration, wherein A 4 is optionally substituted further by 1-10 halogens and/or other groups, the group or groups optionally completing 1-3 additional rings through bonds among themselves and/or 1-5 additional rings when taken together with A , A^, a ring formed by A and A^ together, and/or a bond to carbon atom 9, which halogens and 10 groups taken together include not more than 40 carbon atoms, not more than 24 halogen atoms, and not more than 15 heteroatoms selected from oxygen, nitrogen, silicon, phosphorus and sulfur; J 1 is hydrogen, fluoro, chloro, hydroxy, amino, mono- or di-loweralkylamino, 15 methyl, ethyl, vinyl, ethynyl, propargyl, cyano, methoxy, ethoxy, trifluoromethyl, 2-hydroxyethyl, 2-hydroxypropyl, 3-hydroxypropyl, acetoxy, propanoyloxy, acetyl, propanoyl, hydroxyacetyl, 2-hydroxypropanoyloxy, 3- hydroxypropanoyl, acetamido, propanamido, hydroxyacetamido, 2- hydroxypropanamido, or 3-hydroxypropanamido, (each of which must be 20 situated in the beta position), or J - taken together with A , A , A^ or a ring formed by A 1 together with A completes a 3- to 7-membered substituted or unsubstituted carbocyclic or heterocyclic ring, the substituents of which contain not more than 15 carbon atoms, not more than 10 halogens, and not more than 8 heteroatoms selected from oxygen, nitrogen, silicon, phosphorus and sulfur; 25 J^ is selected from hydrogen, methyl, ethyl, hydroxymethyl, hydroxyethyl, vinyl, ethynyl, allyl, propargyl, n-propyl and isopropyl; provided that, if A 1 and A-" are not linked to form a ring, A 4 must carry a 30 cyclopropyl at positions 13 and 14; the total P j ring skeleton may not comprise any of the following six frameworks, which are derived from various homo-, nor- and homo-nor-steroids; 40 and provided that: for all P j , when are S χ E j taken together and bonded to carbon 6, they may not comprise --CH3, -CH=O, — CH2θ-R es wherein R es is an acyl group, — CH2θ-R et wherein R et is a Ci -Cg hydrocarbon radical or is — C(CH3)2O-linked via the oxygen atom to carbon 5 of P } or ~CH=NNHR j1 wherein R n is a nitrophenyl ring optionally bearing additional substituents; PιS χ Eχ may not include 12-beta-13-alpha-diacetoxy derivatives of compounds having the exact 20-carbon tigliane or 19-carbon 20-nor-tigliane skeleton; PχS χ Eχ may not comprise 20-deoxy-20-chlorocrotophorbolone nor 20-deoxy- 20-chlorophorbol 12,13-diesters wherein the ester groups are both selected from saturated or unsaturated alkanoyl or are both benzoyl; if S χ Eχ is bonded to carbon 6, P j may not carry a ring formed by -OC(CH3)2θ~ bonded in the beta configuration to carbons 3 and 4; and PχS χ Eχ may not comprise 6- deshydroxymethyl-6-carboxyphorbol 12,13-didecanoate or 6- deshydroxymethyl-6-carboxyphorbol 12, 13-diacetate; wherein P2 is a radical of the formula: in the form of an individual isomer, an isomer mixture, a racemate or optical antipode, or a pharmaceutically acceptable salt thereof; wherein B - completes a 6-membered carbocyclic or heterocyclic aromatic ring, optionally substituted by halogen/s and/or other groups, which halogens and groups taken together contain not more than 40 carbon atoms, not more than 24 halogen atoms, and not more than 9 heteroatoms selected from oxygen, nitrogen, silicon, phosphorus and sulfur, the groups being optionally connected to one another and/or to B2 to form 1-3 additional rings; B^ is selected from oxygen, sulfur, sulfoxide, sulfone, monofluoromethylene, difluoromethylene, and a carbon or nitrogen atom optionally substituted by groups having not more than 15 carbon atoms, not more than 24 halogen atoms, and not more than 6 heteroatoms selected from oxygen, nitrogen, silicon, phosphorus and sulfur, and B may be linked to B ~ or K j to form an additional carbocyclic or heterocyclic ring; K s hydrogen, halogen or a group containing not more than 15 carbon atoms, not more than 18 halogen atoms, and not more than 6 heteroatoms selected from oxygen, nitrogen, silicon, phosphorus and sulfur, and K* may be linked to B or B 3 or to both B^ and B^ to form one or more additional carbocyclic and/or heterocyclic rings; B^ is a 2-carbon chain optionally substituted by halogen/s and/or one or more groups which, taken together but excluding S χ Eχ, contain not more than 12 carbon atoms, not more than 6 halogen atoms, and not more than 6 heteroatoms selected from oxygen, nitrogen, and sulfur; provided that, including S χ Eχ, the carbon atom of B"^ bonded to K^ as defined below does not carry — CH 2 OH or — CHCH3OH; K* is selected from oxygen, sulfur — NK — or — CK K— wherein K is hydrogen, hydroxy, methyl, ethyl, fluoro, n-propyl, allyl, or propargyl, and K' is hydrogen, methyl, ethyl, halogen, trifluoromethyl or cyano; K^ and K 4 may be the same or may differ and each may independently be hydrogen, halogen, a substituent group, or may complete an additional ring connecting K^ and K 4 or connecting either K3 or K to K 5, such that K^ and K 4 taken together contain not more than 18 carbon atoms, not more than 24 halogen atoms, and not more than 6 heteroatoms selected from oxygen, nitrogen, silicon, phosphorus and sulfur; K 5 is selected from oxygen, sulfur, sulfoxide, sulfone or -NK --, --NOK -- or o n 0 — CK°K y — wherein K° is hydrogen or a group containing not more than 30 carbon atoms, not more than 24 halogen atoms, and not more than 8 heteroatoms selected from oxygen, nitrogen, silicon, phosphorus and sulfur, and K"- is hydrogen, methyl, ethyl, n-propyl, hydroxy, halogen, allyl, propargyl, cyano, or trifluoromethyl; provided that P2S χ E j may not comprise (-)-l, 10,14- O-trimethylindolactam V, and provided that if B - completes an unsubstituted or substituted carbocyclic aromatic ring, and B is — NH — , — N-(C -C^ linear or branched alkyl or alkanolyl) — , — N- COOCH 2 C 6 H 5 — or — N-COO(CH 3 )3~, and B 3 is — CH 2 CH 2 — , and K- is hydrogen, and K 2 is — NH— , and K is hydrogen, and K 5 is --NH— or — N(C r C3-alkyl)— , then (i) if S χ Eχ is bonded to the carbon atom in B^ that is adjacent to K*, then S χ Eχmay not be — COOMe or — COOEt; and (ii) if S χ is a single bond directed to the carbon atom in B 3 that is adjacent to K , and E j is — CH2 — R , then R is not any of hydrogen, chloro, bromo, Cχ-Cχ saturated or unsaturated linear or branched alkoxy, CH OCH2O — , Cχ-C 2 linear or branched alkanoyloxy, bromoacetoxy, benzoyloxy, azidobenzoyloxy, 3,5-(CH )2" Cg^COO — , methanesulfonyloxy, toluenesulfonyloxy, dansyloxy, (tetrahydro- 2H-pyran-2-yl)oxy, or (Cχ-C6 linear or branched alkyl) n (phenyl)3_ n silyloxy, wherein n is 0-3; wherein P3 is a radical of the formula: in the form of an individual isomer, an isomer mixture, a racemate or optical antipode, or a pharmaceutically acceptable salt thereof; wherein L , L^ and L^ are individually selected from nitrogen or substituted or unsubstituted carbon; D and D each may be a bond or a substituted or unsubstituted carbon atom; D may be linked to L , Lr or both L 1 and L^ to form additional fused carbocyclic and/or heterocyclic substituted or unsubstituted rings; and D^ may be linked to Lr, L^ or both L* and L 3 to form additional fused carbocyclic and/or heterocyclic substituted or unsubstituted rings; D and D 4 each are heteroatom-containing functional groups, the heteroatoms being selected from oxygen, nitrogen, silicon, phosphorus and sulfur; D^ may be linked to L , L ~ " or both L- and L-" to form additional fused substituted or unsubstituted carbocyclic and/or heterocyclic rings; and D 4 may be linked to \-r, L~ or both Lr and L 3 to form additional fused substituted or unsubstituted carbocyclic and/or heterocyclic rings; provided that D - and D^ taken together and Lr- and D 4 taken together both embody at least one oxygen, nitrogen, silicon, phosphorus or sulfur atom separated from the aromatic nucleus by zero or one intervening carbon atom; and L 4 and L are groups which, taken together, contain about 2-40 carbon atoms, not more than 24 halogen atoms, and not more than 6 heteroatoms selected from oxygen, nitrogen, silicon, phosphorus and sulfur; provided that S Q E 0 may not be hydroxymethyl or 1-hydroxyethyl; wherein P is a radical of the formula: SUBSTITUTE SHEET in the form of an individual isomer, an isomer mixture, a racemate or optical antipode, or a pharmaceutically acceptable salt thereof; wherein V s a bond or is a carbon atom carrying substituents individually selected from hydrogen, methyl, and halogen; V™ and V 3 are individually selected from oxygen, sulfur, sulfoxide, and — NV — in which V 4 is hydrogen or a hydrocarbon radical containing not more than 30 carbon atoms; F^ and F^ independently are groups which, taken together, contain 10-40 carbon atoms, not more than 24 halogen atoms, and not more than 8 heteroatoms selected from oxygen, nitrogen, silicon, phosphorus and sulfur, and wherein F 1 and F^ may optionally be linked to form a structure comprising 1-3 rings; F^ is hydrogen or a substituent selected from methyl, ethyl, trifluoromethyl, 2,2,2-trifluoroethyl, cyano, vinyl, ethynyl, allyl, and propargyl; F and F each may be hydrogen or may be hydrocarbon or halogenated hydrocarbon radicals which, taken together, contain not more than 40 carbon atoms, not more than 24 halogen atoms and not more than 8 heteroatoms selected from oxygen, nitrogen, silicon, phosphorus and sulfur, and wherein F and F~* may optionally be linked to form a structure comprising 1-3 rings; provided that V , F , F , F 4 and F 5 taken together contain not more than 50 carbon atoms, not more than 30 halogens and not more than 12 heteroatoms selected from oxygen, nitrogen, sulfur, silicon and phosphorus; and provided that S χ E may not be hydrogen, methyl, chloromethyl, hydroxymethyl, mercaptomethyl, unsubstituted carboxamido, 1-hydroxyethyl or alkanoyloxymethylene; wherein Pg is a radical of the formula: SUBSTITUTE SHEET in the form of an individual isomer, an isomer mixture, a racemate or optical antipode, or a pharmaceutically acceptable salt thereof; wherein U 1 and U^, independently, are selected from hydrogen, azide, halogen, hydroxy, C j .y alkoxy, C j .-γ alkenoxy, Cχ.<7 alkynoxy, thiol, Cχ.y alkanoyl, C j .y saturated or unsaturated alkyl, and cyano; or U and I taken together may be an oxygen atom forming an epoxy group or may be an additional bond forming an unsaturated linkage; U 3 is selected from hydrogen, halogen, Cχ_χ2 alkyl, Cχ-Cχ2 alkenyl, C -Cχ2 alkynyl, Cχ-Cχ2 alkoxy, C j -Cχ2 alkenoxy, Cχ-Cχ2 alkynoxy, and aryl or C - aralkyl wherein the aryl group may be substituted by nitro, halogen, cyano, and/or diloweralkylamino groups; U -U , independently, are selected from hydrogen, halogen, cyano, nitro, aftiino, diloweralkylamino, C\_.η saturated or unsaturated alkyl, hydroxy, Cγ_η saturated or unsaturated alkoxy, C j .y carboalkoxy, Cι__ alkanoyloxy, and azide; and U 7 is selected from hydrogen, Cγ_η saturated or unsaturated alkyl, and C- .η saturated or unsaturated alkanoyl; provided that if S Q E 0 is hydroxymethyl, 1-hydroxyethyl or acetoxymethylene, then S 0 E 0 may not be bonded to C29; wherein Pg is a radical of the formula: in the form of an individual isomer, an isomer mixture, a racemate or optical antipode, or a pharmaceutically acceptable salt thereof; wherein W 1 is selected from hydrogen, halogen, hydroxy, C .5 alkoxy, C .5 alkanoyloxy and cyano; W^ is selected from oxo, hydrogen, hydroxy, cyano, Cγ_η alkyl, Cγ_η alkoxy, G^.-y alkanoyloxy, and halogen; W -W 5 each may be hydrogen or a group containing not more than 30 carbon atoms, not more than 24 halogen atoms, and not more than 8 heteroatoms selected from oxygen, nitrogen, and sulfur, and W 4 and W 5 taken together may form an additional carbocyclic or heterocyclic ring; W b is hydrogen or a group containing not more than 15 carbon atoms, not more than 12 halogen atoms and not more than 5 heteroatoms selected from oxygen, nitrogen, and sulfur; and W , taken together with W 4 and W , may complete an additional carbocyclic or heterocyclic ring; provided that if S 0 E 0 is hydroxymethyl or hydroxyethyl then S 0 E 0 may not be bonded to C25. wherein S χ is selected from the group consisting of S β , S j , S2, S3, S4, Sg and Sg; wherein S β is a single or double bond; wherein a, b, d, e, and g may independently be from 0 to 3; c and f may independently be 0 or 1; the sum of (a+b+c+d+e+f+g) is at least 1 but not more than 12; and if c and fare both 1, then the sum of (d+e) must be at least 1; and X and X' are as defined below; wherein S2 is a chain of atoms of the formula: wherein h, i, k, m, p, and q may be independently be from 0 to 3; j and n may independently be 0 or 1; if j and n are both 1 and 1 is 0, then the sum of (k + m) must be at least 1; if n is 1 and o is 0, then the sum of (p + q) must be at least 1; the sum of (1 + o) is 1-3; and the sum of (h+i+j + k+21+m+n+2o+p+q) is at least 1 but not more than T2; and X, X', Y and Y' are as defined below; wherein S is a chain of atoms of the formula: SUBSTITUTE SHEET wherein r, s, u, y, a', and b' may independently be from 0 to 3; the sum of (t + z) is 0 or 1; the sum of (v + w + x) is 1; the sum of (y + z + a' + b') is at least 1; the sum of (r + s + 2t + u + 2v + 3w + 4x + y + 2z + a' + b') is at least 1 but not more than 12; and Y, Y', Z , lr, and 1? are as defined below; wherein 6 -^ is a chain of atoms defined by: SUBSTITUTE SHEET wherein c', d', e', h', and i' may independently be from 0 to 3; the sum of (f + g') must be 1 or 2; f and g' may independently be 0 or 1; the sum of (c' + d' + e' + f + g' + h' + i') is at least 1 but not more than 12; and M, M', and R i are as defined below; SUBSTITUTE SHEET wherein S5 is a chain of atoms defined by: wherein j', k', m', q', and s' may independently be from 0 to 3; 1' and r' may each be 0 or 1, but the sum of (I' + r') must be 1 or 2; n' and p' may each be 0 or 1, but the sum of (n' + p') must be 0 or 1; the value of o' may be 0-2; if the sum of (n' + p') is 1 and 1' is 0, then q' must be at least 1; if the sum of (n' + p') is 1 and r' is 0, then m' must be at least 1; the sum of (j' + k' + 1' + m' + n' + o' + p' + q' + r' + s') is at least 1 but not more than 12; and Q, ', X, X', and Y are as defined below; wherein Sg is a chain of atoms defined by: LU wherein u', v', w', x', y', z', and m" may each be 0 or 1; t' and a" may each independently be 0-6; the sum of (t' + u' + v' + 2w' + X' + 2y' + z' + a") must be 0-8; b", d", e", ', h", j", k" and n" may each independently be 0 or 1; c", g", i", and 1" may each independently be 0-3; if d" and j" are both 1, then the sum of (g" + i") must be at least 1; if either j" or k" is 1, then 1" must be at least 1; if b" is 1, then the sum of (c" + g" + h" + i" + 1") must be at least 1; if d" is 1, then the sum of (g" + h" + i" + 1") must be at least 1; the sum of (t' + u' + v' + 2w' + x' + 2y' + z + a" + b" + c" + d" + e" + 2 ' + g" + 2h" + i" + j" + k" + 1") must be 0-14; if m" is zero, Rg or Rg may optionally comprise an additional bond to G2 as defined below, thus completing an unsaturated linkage; if n" and b" are zero, Rg or Rg may optionally comprise an additional bond to G , thus completing an unsaturated linkage; one of the substituents Rg-Rg and/or one of the substituents RgRg^may optionally comprise the same or different values of G , as defined below; M, M', Q, Q', Q", Q"\ X, X', X", Y, Y', Z 4 , Z 4 ', Z 5 and Z 5 ' are as defined below; and wherein, for Sχ-Sg, R{ through R^may be the same or different and each may be hydrogen, halogen or an acyclic substituent containing not more than 20 carbon atoms, not more than 16 halogen atoms, and not more than 6 heteroatoms selected from oxygen, nitrogen, sulfur, silicon and phosphorus; one substituent selected from R), R|, R , R , Rg, Rg and Rg may optionally comprise an additional bond completing an unsaturated linkage to P^; one or two of the substituents optionally comprise the same or different values of G , as defined below; R 12 3 , R 1 1 4 , n additonal bond to Ei , thereby completing an unsaturated linkage; one of the substituents Rj-R ^may be linked to either the atom in P χ that carries the S j chain or to an atom in P χ adjacent thereto, to form a 4-8 membered ring optionally containing 1-4 identical or different ring hetero members selected from X and =N-, the ring being optionally substituted by 1-8 identical or different substituents selected from halogen, hydroxy, methoxy, ethoxy, methyl, ethyl, cyano, azide, nitro, hydroxymethyl, 1-hydroxyethyl, 2- hydroxy-2-propyl, CF 3 , OCF 3 , SH, SCH3, SOCH3, SCF3, COOH, COOCH3, COCH3, CH=O, acetoxy, amino, mono- or dialkylamino totalling 1-4 carbon atoms inclusive, acetamido, N-methylacetamido, carboxamido, N-alkylated carboxamido containing 1-4 carbon atoms inclusive, hydroxyacetyl and hydroxyacetoxy; provided that, for any given S j , S2, S3, S4, S5 or Sg, but excluding P χ and E j : the total of carbon atoms is 25 or less; the total of halogen atoms is 16 or less; the total of oxygen atoms is 6 or less; the total of nitrogen atoms is 4 or less; the sulfur, silicon and phosphorus atoms each total 3 or less; and the total of oxygen, nitrogen, silicon, phosphorus and sulfur atoms together is 8 or less; " may be the same or different and are selected from: 0 Q Q ,_ I I I I I I 0 ' ? Q ' • I I — N — — N — — P — — p O R 3 R 4 p5 U \ R 2 H R X R x SUBSTITUTE SHEET -143- Rf. χ 1 ° wherein RJ ζ , R , Rχ and Rj may independently be hydrogen; Rj£ through may be the same or different and each may be an acyclic substituent containing 1-20 carbon atoms, not more than 16 halogen atoms, and not more than 6 heteroatoms selected from oxygen, nitrogen, and sulfur, such that for any substituent the oxygen atoms total 4 or less, the nitrogen atoms total 4 or less, and the sulfur atoms total 2 or less; R , R , R * and Rj^may independently be hydroxy; Q and Q * are as defined below; RJ j may optionally represent an additional bond to P χ , thus completing an unsaturated linkage; one or two of the substituents Rχ-R j may optionally comprise the same or different values of G , as defined below; wherein Y and Y' may be the same or different and are selected from: O / \ a n d C — C— SUBSTITUTE SHEET -144- wherein R^ and R , and R and Ri^, each pair being cis or trans relative to one another, may be the same or different and each may be hydrogen or an acyclic substituent containing not more than 20 carbon atoms, not more than 16 halogen atoms, and not more than 6 heteroatoms selected from oxygen, nitrogen, and sulfur, such that for any substituent the oxygen atoms total 4 of less, the nitrogen atoms total 4 or less, and the sulfur atoms total 2 or less; R^r and Ry^ may also independently be halogen; one or two of the substituents Rγ-Rγ may optionally comprise the same or different values of G , as defined below; one of the substitents Rχ-R> and Rγ-Rγ may be linked to either the atom in P χ that carries the chain containing X, X', and/or X" or to an atom in P χ adjacent thereto, to form a 4-8 membered ring defined as for the analogous Rj-Rg -containing ring above; wherein Z 1 is selected from: N _N — o— N — N— O CzzN- an d ■ N=C I R •zl Rl lr is selected from -C.= — N — — N— NrrC — -C zN— O- -N: :C — I I R 1 5 R 1 6 Z 3 is selected from: O 0 • Z 4 and Z 4 independently may be: ■ N Z° and Z independently may be: o r -O— N- I R 30 wherein the substituents from hydrogen, halogen and radical containing 1-12 carbon atoms and optionally containing 0-12 halogens and 0-6 heteroatoms selected from oxygen, nitrogen and sulfur; one of the substituents R 5 £ may be linked to either the atom in P χ that carries the chain containing Z- or to an atom in P χ adjacent thereto, to form a saturated, unsaturated, or aromatic, carbocyclic or heterocyclic 4-8 membered ring optionally containing 1-4 other identical or different hetero ring members selected from O, S, =N-, and NH, the ring being optionally substituted on its carbon and/or NH members by 1-8 identical or different substituents selected from halogen, hydroxy, methoxy, ethoxy, methyl, ethyl, cyano, azide, nitro, hydroxymethyl, 1-hydroxyethyl, 2-hydroxy-2-propyl, CF 3 , OCF 3 , SH, SCH3, SOCH3, SCF 3 , COOH, COOCH3, COCH3, CH=O, acetoxy, amino, mono- or dialkylamino totalling 1-4 carbon atoms inclusive, acetamido, N-methylacetamido, carboxamido, N-alkylated carboxamido containing 1-4 carbon atoms inclusive, hydroxyacetyl and hydroxyacetoxy; R2 may comprise G^ as defined below; an optional ring may be formed between R 6 and P χ as described above for Rx-Rx 2 ; R£, RJ, R 1 Z > R26 Z or Rjj ? may comprise an additional bond to P χ , thus completing an unsaturated linkage; and only one of the substituents be substituted or unsubstituted phenyl or benzyl; wherein M and M' independently may be: 0 r -N — 1 2 wherein Rfø and Rfø may be the same or different and each may be hydrogen or a saturated or singly or multiply unsaturated, straight or branched, acyclic substituent containing 1-20 carbon atoms, not more than 16 halogen atoms, and not more than 6 heteroatoms selected from oxygen, nitrogen, and sulfur, in which the oxygen atoms total 4 or less, the nitrogen atoms total 4 or less, and the sulfur atoms total 2 or less, the heteroatoms being preferably situated in functional groups selected from hydroxy, amino, thiol, nitro, azide, ether, thioether, aldehyde, keto, carboxy, ester, amide, cyano, nitroguanidine, and cyanoguanidine; Rfø may optionally comprise an additional bond to P χ group, thus completing an unsaturated linkage; R j f or Rfø may optionally comprise the same or different values of G , as defined below; Rfø or Rjj j may be linked to either the atom in P χ that carries the chain containing M and/or M' or to an atom in P χ adjacent thereto, to form a 4-8 membered ring defined as for the analogous Rj-R^containing ring above; wherein Q-Q'" independently may be: :0 N -Rj o r =ZZN — 0— Rn Q wherein ' RΛ and Rζ may be the same or different and each may have the values specified above for Rfø and Rfø; Rfo and/or R may optionally comprise the same or different values of G , as defined below; Rζ may be linked to either the atom in P χ that carries the chain containing Q and/or Q' or to an atom in P χ adjacent thereto, to form a 4-8 meme'bered ring defined as for R{-R ( containing ring above; wherein R^-R^ are independently selected from: Q Q ' Q " I I I I I I -C- ■ S- -S— I I O I I R≤ R Q wherein RA and R may be the same or different and each may he selected from halogen and the values specified above for R^ j and R J; R and/or R7 may optionally comprise the same or different values of G , as defined below; Q and ' are as defined above; one of R and R? may be linked to either the atom in P χ bonded to the chain that carries RQ or to an atom in P χ adjacent thereto, to form a 4-8 membered ring defined as for Rj-R^containing ring above; wherein G and G^ independently comprise a group containing 1-3 fused or separate, saturated, unsaturated or aromatic 4-8 membered rings, each ring optionally containing 1-4 identical or different hetero ring members selected from X and =N-, each ring being optionally substituted on its carbon and/or NH members by 1-8 identical or different substituents, preferably selected from halogen, hydroxy, methoxy, ethoxy, methyl, ethyl, cyano, azide, nitro, hydroxymethyl, 1- hydroxyethyl, 2-hydroxyethyl, 2-hydroxy-2-propyl, CF3, OCF3, SH, SCH3, SOCH3, SCF3, COOH, COOCH3, COCH3, CH=O, acetoxy, amino, mono- or dialkylamino totalling 1-4 carbon atoms inclusive, acetamido, N- methylacetamido, carboxamido, N-alkylated carboxamido containing 1-4 carbon atoms inclusive, hydroxyacetyl and hydroxyacetoxy; wherein for G 1 the optional second and third rings may be fused to the first ring and/or to one another or may be separate rings connected to one another and/or to the atom bearing G- by a single or double bond or by an intervening substituted or unsubstituted, linear or branched, saturated or unsaturated chain containing not more than 8 carbon atoms, not more than 8 halogens, and not more than 4 heteroatoms selected from oxygen, nitrogen, silicon, phosphorus and sulfur; and wherein for G-" the first ring is singly or doubly bonded to P χ or to a component atom of the S β chain connecting P χ and G and the optional second and third rings may be fused to the first ring or to one another or may be separate rings connected to one another and/or to the first ring by single or double bonds or by an intervening substituted or unsubstituted, linear or branched, saturated or unsaturated chain containing not more than 8 carbon atoms, not more than 8 halogens, and not more than 4 heteroatoms selected from oxygen, nitrogen, silicon, phosphorus and sulfur; wherein E j is selected from =O, =S, =NH, =NOR£ wherein Rg is hydrogen or a CJ-CQ normal or branched alkyl radical, hydrogen, halogen, -OH, -SH, -NH 2 , -NH-NH 2 , -N 3 , -CN, -NO, -NO 2 , -NHOH, -ONH 2 , or is selected from : T~ ' D Rf2 z=CRn£4nR5 T 2 •s i τ 5 τ 5 'τ 5 " 1 " A I I -s- T I I I I O o -T— P— T' • P— T' wherein T ~ is selected from — O-, — S-, and — NH— ; T 2 is selected from =O, =S, and =N-R , in which R may be hydrogen, hydroxy, cyano, or nitro; T^ is selected from =O and =S; \, T 3 , rtnd T 4 ' are independently selected from -OH, -NH 2 , -SH, -N 3 , - NH~NH 2 , and -NH-ORj^, in which R may be hydrogen, C^ alkyl or Cγ. 3 ac y l ; T may also be hydrogen or halogen; T -T^ are independently selected from hydrogen and hydroxy; T~- may also be halogen; R£ is selected from hydrogen, halogen, hydroxy, nitro, nitroso, cyano, azide, - NH 2 , --NH--OH, -SH, -O-NH 2 , -NH-NH 2 , -T 1 ~C(=T )-T 3 , -C(=T 2 )- T 3 , -SiT 5 T 5 T 5 ", -T 1 -S(=O)(=T )-T 4 , -S(=O)(=T 2 )-T 4 , --T 1 »P(--T 4 )-- T 4 ', -P(.-T 4 )~T 4 ', -T1~P(=T 2 ')(-T 3 )~T 4 , and -P(=T 2 ')(~T 3 )-T 4 ; Rg and Rg are individually selected from hydrogen, --C(=T^)--T , cyano, nitro, azide, halogen and a C^-Ci g straight or branched chain, saturated, unsaturated and/or aromatic-containing alkyl moiety optionally containing not more than 10 halogen atoms and not more than 4 heteroatoms selected from oxygen, nitrogen and sulfur; and if Rg is cyano or — C(=T^)~T , then Rg or Rjr may optionally be selected from -SiT 5 T 5 T 5 ", -T 1 -P(=T 2 ')(~T 3 )~T 4 , and ~P(=T 2 ')(~T 3 )-T 4 ; and R and Rg are individually selected from hydrogen, halogen, cyano, nitro, — C(=T 2 )~T 3 , ~T 1 ~C(=T 2 )~T 3 , -CRJ R|R|, ~SiT 5 T 5 T 5 ", ~S(=O)(=T 2 )~ T 4 , and -P(=T 2, )(-T 3 )-T 4 . 4. A compound of Claim 3 wherein Sx and PI taken together comprise: (i) dihalomethyl, trihalomethyl, -N3, -NH2, -CN, -COOH, -CH=CHCOOH, -C≡CCOOH, -CSSH, -COSH, -SO2H, -SO3H, -P(=O)(Ra)OH, - P(=S)(Ra)OH, -P(=O)(ORa)OH, -P(=S)(ORa)OH, -CH=NOH, - CH=NOCH3, -CHN(→O)CH3, -C(CH3)=NOH, -CH=CHRa, -C≡C-Ra, - CH2C≡C-Ra, -Si(CH3)2OH, -Si(OH)2CH3, -SiCH3)2F, -Si(CH3)2Ra, - CH2Si(CH3)2Ra, or =CHRa, in which Ra is hydrogen or Cl-12 linear or branched, saturated, unsaturated and/or aromatic hydrocarbon optionally substituted by not more than 16 halogens; or (ϋ) -CH2- or ~CH(CH3)~, to either of which is bonded -Ra, -N3, -NH2, - CN, -COOH, -COSH, -CSSH, -Si(CH3)2OH, -Si(OH)2CH3, ~SiCH3)2F, - SO2H, -SO3H, -PO3H2, ~P(=O)(Ra)OH, -P(=S)(Ra)OH, - P(=O)(ORa)OH, -P(=S)(ORa)OH, the o-, m- or p-isomer of-M- C6H4CH2-T3, the o-, m- or p-isomer of --C6H4CH2--T3, -SRa, - SCH2CH2OH, -S(=O)-CH2CH2OH, -S(CH2)3OH, -S(CH2)4OH, - SCH2CH2SH, -M-C(=T2)-M'~Ra except -OC=ONH2, -OCH2C(=O)CH3, -OCH2C(=NOH)CH3, the o-, m- or p-isomer of-M-C(=T2)-M'--C6H4-T3, or the o-, m- or p-isomer of-M~C(=T2)-M'-C6H4CH2-T3. 5. A compound of Claim 3 wherein P j is PJR: wherein carbons (1 and 2) or (2 and 3) may be joined by a double bond; carbons (5 and 6) or (6 and 7) may be joined by a double bond; S j E | may be bonded to carbon 5, 6 or 7; R A1 re P resents not more than 8 identical or different substituents bonded independently via single and/or double bonds to carbons 1, 2 and/or 3, which substituents may independently be halogen(s) and/or other groups, which halogens and groups taken together contain a total of not more than 30 carbon atoms, not more than 24 halogen atoms and not more than 9 heteroatoms selected from oxygen, nitrogen, silicon, phosphorus and sulfur; R^ represents not more than 6 identical or different substituents bonded independently via single and/or double bonds to carbons 5, 6 and/or 7, which substituents may independently be halogen(s) and/or other groups, which halogens and groups taken together contain not more than 12 carbon atoms, not more than 8 halogen atoms, and not more than 5 heteroatoms selected from oxygen, nitrogen, silicon, phosphorus and sulfur; and R£4 represents not more than 10 identical or different substituents bonded independently via single or double bonds to carbons 9, 11, 12, 13 and/or 14, which substituents may independently be halogen(s) and/or other groups, the group or groups optionally completing 1-3 additional rings through bonds among themselves and/or 1-5 additional rings when taken together with A , A , a ring formed by A* and A~" together, and/or a bond to carbon atom 9, which halogen and groups taken together, include not more than 50 carbon atoms, not more than 24 halogen atoms, and not more than 15 heteroatoms selected from oxygen, nitrogen, silicon, phosphorus and sulfur. 6. A compound of Claim 5 wherein carbons 13 and 14 of Pi ^ carry a substituted or unsubstituted cyclopropyl moiety, forming P^p: wherein the p^ and R^g radicals may independently be hydrogen, halogen and/or other groups, which halogens and groups taken together contain a total of not more than 30 carbon atoms, not more than 24 halogen atoms and not more than 9 heteroatoms selected from oxygen, nitrogen, silicon, phosphorus and sulfur. 7. A compound of Claim 6 wherein the Pi p carbon 2 carries a methyl group, J is hydroxy, carbon 9 carries a hydroxy group in the alpha configuration, carbons 10 and 14 carry alpha hydrogens, carbon 11 carries a methyl group in the alpha configuration and p& and R^g are both methyl, forming P^pp: SUBSTITUTE SHEET ) mpound of Claim 5 wherein PJR carries an orthoester moiety bonded to the 6- membered ring via one orthoester oxygen atom in the alpha configuration to carbon 9 and via two orthoester oxygen atoms in the alpha configuration to any two of carbons 12-14, forming PI RR: wherein R j ^ represents hydrogen, halogen or other group, the group optionally completing 1 additional ring to carbon 1, which group includes not more than 30 carbon atoms, not more than 16 halogen atoms, and not more than 9 heteroatoms selected from oxygen, nitrogen, silicon, phosphorus and " sulfun SUBSTITUTE SHEET 9. A compound of Claim 8 wherein the P I RR carbon 2 carries a methyl group, J 1 is hydroxy, carbon 10 carries a hydrogen atom in the alpha configuration, carbon 11 carries a methyl group in the alpha configuration and carbon 13 carries an isopropenyl group, forming Pi RRR: 10. A compound SUBSTITUTE SHEET wherein R j gi represents not more than 8 identical or different substituents bonded independently via single and/or double bonds to carbons 1, 2 and/or 3, which substituents may independently be halogen(s) and/or other groups, which halogens and groups taken together contain a total of not more than 30 carbon atoms, not more than 24 halogen atoms and not more than 9 heteroatoms selected from oxygen, nitrogen, silicon, phosphorus and sulfur; RA3I represents not more than 6 identical or different substituents bonded independently via single and/or double bonds to carbons 5, 6 and/or 7, which substituents may independently be halogen(s) and/or other groups, which halogens and groups taken together contain not more than 12 carbon atoms, not more than 8 halogen atoms, and not more than 5 heteroatoms selected from oxygen, nitrogen, silicon, phosphorus and sulfur; carbon atom 9 may be unsubstituted or may carry a substituent defined as for ^A21 aDove 5 and R^4 j represents not more than 10 identical or different substituents bonded independently via single or double bonds to carbons 9, 11, 12, 13 and/or 14, which substituents may independently be halogen(s) and/or other groups, the group or groups optionally completing 1-3 additional rings through bonds among themselves and/or 1-5 additional rings when taken together with A , A a ring formed by A- and A^ together, and/or a bond to carbon atom 9, which halogen and groups taken together, include not more than 50 carbon atoms, not more than 24 halogen atoms, and not more than 15 heteroatoms selected from oxygen, nitrogen, silicon, phosphorus and sulfur. 11. A compound of Claim 10 wherein P j j carbons 13 and 14 of carry a substituted or unsubstituted cyclopropyl moiety, thus forming P ] ] s j : wherein the R^δ j and R^gi radicals may independently be hydrogen, halogen and/or other groups, which halogens and groups taken together contain a total of not pore than 30 carbon atoms, not more than 24 halogen atoms and not more than 9 heteroatoms selected from oxygen, nitrogen, silicon, phosphorus and sulfur. 12. A compound of Claim 11 wherein P I TJ V J carbon 2 carries a methyl group, J- is hydroxy, carbon 11 carries a methyl group in the alpha configuration, carbon 14 carries an alpha hydrogen and R^ and R^g j are both methyl, forming 13. A compound of Claim 3 wherein P2 isP2NN : wherein Kg j represents 1-3 identical or different substituents located independently at carbons 5, 6, and/or 7, which substituents may independently be hydrogen, halogen and/or other groups which, taken together, contain not more than 40 carbon atoms, not more than 24 halogen atoms, and not more than 9 heteroatoms selected from oxygen, nitrogen, silicon, phosphorus, and sulfur, the groups being optionally connected to one another, to K3 and/or to Kg2 to form 1-3 additional carbocyclic or heterocyclic rings; 1 and wherein K β 2 is hydrogen or a group which contains not more than 20 carbon atoms, not more than 24 halogen atoms, and not more than 6 heteroatoms selected from oxygen, nitrogen, silicon, phosphorus and sulfur, this group being optionally connected to B j or K j to form an additional carbocyclic or heterocyclic ring. 14. A compound of Claim 13 wherein K j and K3 are hydrogen and K2 is -NH— , forming P NNN : SUBSTITUTE SHEET and K4 is hydrogen or other group containing not more than 20 carbon atoms, not more than 24 halogen atoms, and not more than 9 heteroatoms selected from oxygen, nitrogen, silicon, phosphorus and sulfur, the group being optionally connected to Kg to form an additional ring. 15. A compound of Claim 14 wherein P NNN * s se i ecte d from P2L and P2 , wherein P 2L is: whereip K β ^> is hydrogen, halogen or other group which contains not more than 40 carbon atoms, not more than 24 halogen atoms, and not more than 9 heteroatoms selected from oxygen, nitrogen, silicon, phosphorus and sulfur, this group being optionally connected to K β 2 t form an additional ring; and wherein P2T is wherein a four-carbon saturated, unsaturated or aromatic ring connects positions 6 and 7 and substituents K1 . Q -K13 may independently be absent in favor of unsaturated linkages or may be hydrogen, halogen and/or other groups which, taken together, contain not more than 36 carbon atoms, not more than 24 halogen atoms, and not more than 9 heteroatoms selected from oxygen, nitrogen, silicon, phosphorus and sulfur. 16. A compound selected from the group consisting of: (i) 12,20-dideoxy-20-chlorophorbol 13-angelate; (ii) 20-deoxy-20-bromophorbol 12-myristate 13-acetate; (iii) 20-deoxy-20-iodophorbol 12-myristate 13-acetate; (iv) 20-deoxy-20-chlorophorbol 12,13-bis(2,4-difluorophenylacetate); (v) 20-deoxy-20-fluorophorbol 12, 13-bis(2,4-difluorophenylacetate); (vi) 12-beta,13-bis(2,4-difluorophenylacetoxy)-4,9-dihydroxy-l,6(20),7- tigliatrien-3-one; 12-beta,13-bis(2,4-difluorophenylacetoxy)-4,9-dihydroxy-7- fl uoro- 1 ,6(20)-tigliadien-3-one; (vii) 20-deoxy-20-cyanophorbol 12-myristate 13-acetate; (viii) 20-deoxy-20-dimethylaminophorbol 12-myristate 13-acetate; (ix) 12-beta-myristoyloxy- 13-acetoxy-4,9-dihydroxy-7-hydroxymethyl- l,6(20)-tigliadien-3-one; (x) 20-Deoxy-3-deoxo-3-hydroximino-20-n-propylthiophorbol 12,13- Bis(2',4'-difluorophenylacetate); (xi) 6-Deshydroxymethyl-6-carbomethoxyphorbol 12, 13-Bis(2',4'- difluorophenylacetate); (xii) 20-Deoxy-20-mercaptomethylphorbol 12,13-Bis(2',4'- difluorophenylacetate); (xiii) 20-deoxy-20-(l'-azidoethyl)phorbol 12-(4'-biphenyl)acetate 13-[3- (3,5-difluorophenyl)propionate]; (xiv) 20-Deoxy-20-(alpha-benxylthio)phorbol 12,13-Bis(2',4'- difluorophenylacetate); (xv) 20-Deoxy-20-methylaminophorbol 12,13-Bis(2',4'- difluorophenylacetate) (xvi) phorbol 12-(3-phenoxy)benzoate 13-butyrate 20-carbamate; (xvii) 20-deoxy-20-(2-hydroxyethylthio)-3-deoxo-3-hydroximinophorbol 12,13-bis(pentafluorophenylpropionate); and (xviii) 12-beta-Myristoyloxy- 13-acetoxy-4,9-dihydroxy- 1 ,6(20)-tigladien- 3-one. 17. A compound of Claim 3 wherein E j is selected from halogen, -COOH, -CH N3, ~CH 2 SH, -CH 2 NH 2 , -CH 2 COOH, -CH=NOH, -CH 2 P(=O)(OH) 2 , - CH P(=O)(CH 3 )OH, -CH 2 SO 2 H and -CH 2 SO 3 H. 18. A compound of Claim 17 selected from the group consisting of: (i) 20-deoxy-12,13-bis-O-(2,4-difluoroethyl)phorbol 20-sulfonic acid; (ii) 20-deoxyphorbol 12,13-bis(2,4-difluorophenylacetate) 20-sulfinic acid; (iii) 20-deoxyphorbol 12,13-bis(2,4-difluorophenylacetate) 20- phosphonic acid; (iv) 20-deoxyphorbol 12,13-bis(2,4-difluorophenylacetate) 20- methylphosphinic acid; (v) 20-deoxy-20-azidophorbol 12, 13-bis(2,4-difluorophenylacetate); (vi) 20-deoxy-20-mercaptophorbol 12, 13-bis(2,4-difluorophenylacetate); (vii) 20-deoxy-20-aminophorbol 12, 13-bis(2,4-difluorophenylacetate); (viii) 20-deoxy-20-hydroximinophorbol 12,13-bis(2,4- difluorophenylacetate); (ix) 20-deoxy-20-carboxyphorbol 12, 13-bis(2,4-difluorophenylacetate); (x) 20-des(hydroxymethyl)-6-chlorophorbol 12,13-bis(2,4- difluorophenylacetate); (xi) 20-des(hydroxymethyl)-6-bromophorbol 12,13-bis(2,4- difluorophenylacetate); (xii) 20-deoxy-20-carboxyphorbol 12-myristate 13-acetate; (xiii) 20-Deoxy-3-deoxo-3,20-bis(hydroximino)phorbol 12, 13-Bis(2',4'- difluorophenylacetate) ; (xiv) 6-Deshydroxymethyl-6-carboxyphorbol 12,13-Bis(2',4'- difluorophenylacetate) (xv) 6-deshydroxymethyl-6-carboxy-3-deoxo-3-benzoyloxyphorbol 12- butyrate 13-(2',4'-difluorobenzoate); (xvi) 6-deshydroxymethyl-6-carboxyphorbol 12-myristate 13-acetate; (xvii) 6-deshydroxymethyl-6-carboxyphorbol 12-(3,5-difluorocinnamate) 13-[3-(2',4'-difluorophenyl)propionate]; and (xviii) 12-deoxy-6-deshydroxymethyl-6-carboxyphorbol 13-decanoate. 18. A compound selected from the group consisting of: (i) 20-O-(4-hydroxy-2-butynyl)phorbol 12,13 bis(2',4'- difluorophenylacetate); (ii) 20-O-(4-hydroxy-2-butenyl)phorbol 12-(4'-biphenyI)acetate 13- acetate; (iii) 20-O-acetonylphorbol 12-[(2,2-dimethyl)(2',4'-difluorophenyl)acetate 13-butyrate; (iv) 20-O-(2-propyl)phorbol 12-myristate 13-acetate; and (v) 20-O-(3-hydroxypropyl)phorbol 12-myristate 13-acetate. 19. A compound selected from the group consisting of: (i) 20-deoxy-20-(N,N',N'-trimethylhydrazinyl)phorbol 12,13 bis(2',4'- difluorophenylacetate); and (ii) phorbol 12-myristate 13-acetate 20-(N',N'-diethylhydrazone). 20. A compound selected from the group consisting of: (i) 6-Deshydroxymethyl-6-carbomethoxyphorbol 12,13-Bis(2',4'- difluorophenylacetate) (ii) 12-deoxy-6-deshydroxymethyl-6-[N-(2- hydroxyethyl)carboxamido]phorbol 13-decanoate; (iii) 6-Deshydroxymethyl-6-[N-(2,3-dihydroxypropyl)carboxamido]- phorbol 12,13-Bis(2 , ,4'-difluorophenylacetate) 1. A compound of Claim 3 wherein S4E 0 taken together comprise an aminocarbonyloxymethylene group or a CJ-CJQ saturated or unsaturated alkyl- , aralkyl- or arylaminocarbonyloxymethylene group. 22. A compound of Claim 21 selected from the group consisting of: (i) phorbol 12-myristate 13-acetate 20-methyl-carbamate; (ii) phorbol 12-myristate 13-acetate 20-ethyl-carbamate; (iii) phorbol 12-myristate 13-acetate 20-n-propyicarbamate; and (iv) phorbol 12-myristate 13-acetate 20-n-butylcarbamate. 23. A compound selected from the group consisting of: (i) 20-Deoxy-20-acetonylthiophorbol 12,13-Bis(2',4'- difluorophenylacetate); and (ii) 20-O-acetonylphorbol 12-[(2,2-dimethyl)(2',4'-difluorophenyl)acetate 13-butyrate. 24. A compound selected from the group consisting of: (i) phorbol 12-myristate 13-acetate 20-(2-hydroxymethyl phenyl) ether; (ii) 20-deoxy-20-(l-tetrazolyl)phorbol 12-myristate 13-acetate; (iii) 20-Deoxy-20-(l-imidazolyl)phorbol 12,13-Bis(2',4'- difluorophenylacetate); (iv) 20-Deoxy-20-(2-imidazolyl)phorbol 12,13-Bis(2',4'- difluorophenylacetate); and (v) 20-Deoxy-20-[(3-hydroxymethylphenyl)aminophorbol 12, 13-Bis(2\4'- difluorophenylacetate). 25. A compound selected from the group consisting of: (i) 6-deshydroxymethyl-6-oxoresiniferonol 9, 13, 14-orthophenylacetate; and (ii) mezerein 20-carbamate. 26. A compound selected from the group consisting of: (i) 20-deoxyresiniferonol 9,13,14-orthophenylacetate 20-sulfonic acid; (ii) 20-deoxyresiniferonol 9,13,14-orthophenylacetate 20-sulfinic acid; (iii) 20-deoxyresiniferonol 9,13,14-orthophenylacetate 20-phosphonic acid; (iv) 20-deoxyresiniferonol 9,13,14-orthophenylacetate 20- methylphosphinic acid; (v) 20-deoxy-20-azidoresiniferonol 9,13,14-orthophenylacetate; (vi) 20-deoxy-20-mercaptoresiniferonol 9, 13, 14-orthodecanoate; (vii) 20-deoxy-20-aminoresiniferonol 9,13,14-orthophenylacetate;; (viii) 20-deoxy-20-hydroximinoresiniferonol 9,13,14- orthophenylacetate; ; (ix) 20-deoxy-20-carboxyresiniferonol 9,13,14-ortl ophenylacetate; (x) 6-de_>hydroxymethyl-6-chlororesiniferonol 9, 13, 14-orthodecanoate; (xi) 6-deshydroxymethyl-6-bromoresiniferonol 9, 13, 14-orthodecanoate; and (xii) 6-deshydroxymethyl-6-carboxyresiniferonol 9,13,14- orthophenylacetate. 27. A compound selected from the group consisting of: (i) 20-deoxyresiniferonol 9,13,14-orthophenylacetate 20-acetonyl thioether; and (ii) mezerein 20-acetonyl ether. 28. A compound selected from the group consisting of: (i) 20-deoxy-20-(N,N',N'-trimethylhydrazinyl)resiniferonol 9, 13, 14- orthodecanoate; and (ii) 5-hydroxy-6,7-alpha-epoxy resiniferonol 9, 13, 14-orthodecanoate 20- (N'-acetyl)hydrazone. 29. A compound selected from the group consisting of: (i) resiniferonol-9, 13, 14-orthophenylacetate 20-ethylcarbamate; (ii) 6-deshydroxymethyl-6-[N-(2'- hydroxyethyl)carboxamido]resiniferonoI-9, 13, 14- orthophenylacetate; and (iii) 6-deshydroxymethyl-6-carbomethoxyresiniferonol-9, 13, 14- orthophenylacetate. 30. A compound selected from the group consisting of: (i) 20-O-acetonylresiniferonol-9, 13, 14-orthophenylacetate; and (ii) 20-O-[ 1 '(2'-hydroximinopropyl)]resiniferonol-9, 13, 14- orthophenylacetate. 31. A compound selected from: (i) 20-O-(4- hydroxyphenoxy)carbonylresiniferonol 9,13,14- orthophenylacetate; and (ii) 20-O-(2-hydroxyphenoxy)carbonylmezerein. 32. A compound selected from the group consisting of: (i) 6-des(hydroxymethyl)-6-carboxyingenol; (ii) 6-des(hydroxymethyl)-6-carboxyingenol 3-benzoate; (iii) 6-des(hydroxymethyl)-6-carboxyingenol 3-(2',4'- difluorobenzyl)carbamate; (iv) 6-des(hydroxymethyl)-6-chloroingenol 3-benzoate; (v) 6-des(hydroxymethyl)-6-chloroingenol 3-(2',4'- difluorobenzyl)carbamate; and (vi) 20-deoxy-20-azidoingenol 3-(2',4'-difluorobenzyl)carbamate. 33. A compound selected from the group consisting of: (i) ingenol 20-methylcarbamate; and (ii) 9-deoxy-9-butylideneingenol 20-methylthiocarbamate. 34. A compound selected from the group consisting of: (i) ingenol-3-benzoate 20-acetonyl ether; and (ϋ) ingenol 3-biphenylcarbamate 20-acetonyl ether. 35. A compound selected from: (i) 20-O-(4- hydroxyphenoxy)carbonylingenol 3-benzoate; and (ii) 20-O-(4-hydroxyphenoxy)carbonylingenol 3-(2',4'- difluorophenylcarbamate. 36. A compound selected from the group consisting of: (i) rac-14-O-(N-Methyl)carbamoylindolactam V; (ii) rac-14-O-(N-Methyl)carbamoyl-l-N-diphenylphosphoryl-(iii) indolactam V; (iv) rac- 14-O-(N-Methyl)carbamoyl- 1 -N-(2-triphenylphosphonium)- ethylindolactam V, methanesulfonate salt; (v) rac- 14-O-(N-Methyl)carbamoyl- 1-N-trimethylsilymethyl-indolactam V; (vi) 14-O-(N-Methyl)carbamoyl-7-octyl-(9S,12S)-indolactam V; (vii) 14-O-[(Diisopropylamino)methoxy]phosphinyl-7-octyl-(9S,12S)-indolactam V; (viii) 14-O-(Dimethyl)thiophosphoryl-7-octyl-(9S, 12S)-indolactam V; (ix) 14-Deshydroxy- 14-(N-methanesulfonyl)amino-7-octyl-(9S, 12S)-indolactam V; (x) 14-Deshydroxy-14-triphenylphosphonium-7-octyl-(9S, 12S)-indolactam V, iodide salt; (xi) 14-O-[N-(S)-(l'-Naphthyl)ethyl]carbamoyl-7-octyl-(9R, 12R)-indolactam V; (xii) 14-O-[N-(S)-(l'-Naphthyl)ethyl]carbamoyl-7-octyl-(9S,12S)-indolactam V; (xiii) 14-O-[N-(R)-(l'-Naphthyl)ethyl]carbamoyl-(9R,12R)-indolactam V; (xiv) 14-O-[N-(R)-(l'-Naphthyl)ethyl]carbamoyl-(9S,12S)-indolactam V; and (xv) 14-O-Carbamoyl-7-octyl-(9S,12S)-indolactam V. 37. A compound selected from the group consisting of: (i) 20-deoxy-20-(2-hydroxyethylthio)phorbol 12-butyrate; (ii) 20-deoxy-20-(2-hydroxyethylthio)phorbol 12,13-dibutyrate; (iii) 20-deoxy-20-(2-hydroxethylthio)phorbol 12-myristate 13-acetate; (iv) 20-deoxy-20-[(2-hydroxethyl)methyl-amino]phorbol 12-myristate 13- acetate; (v) 20-deoxy-20-(3-hydroxypropylthio)phorbol 12,13-bis(2,4- difluorophenylacetate); (vi) 20-deoxy-20-N-methylaminophorbol 12-myristate 13-acetate; (vii) phorbol 12-myristate 13-acetate 20-cholinephosphate; (viii) 20-deoxy-20-(2,3-dihydroxypropylthio)phorbol 12, 13-bis(2',4'- difluorophenylacetate) ; (ix) 20-deoxy-20-[2-(formylamino)ethylthio]phorbol 12-myristate 13- acetate; (x) 20-deoxy-20-[2-(methylsulfonylamino)ethylthio]phorbol 12-myristate 13-acetate; (xi) 20-deoxy-20-propylthiophorbol 12,13-bis(2',4'- difluorophenylacetate); 5 (xii) 20-deoxy-20-(2-mercaptoethylthio)phorbol 12,13-bis(2 , ,4'- difluorophenylacetate); (xiii) 20-deoxy-20-(2-hydroxyethylthio)phorbol 12,13-[O,O'- bis(isopropyldimethylsilyl)]; (xiv) 20-deoxy-20-(2-carboxyethylthio)phorboI 12-(4'-biphenyl)acetate 10 13-[3-(3,5-difluorophenyl)propionate]; (xv) 20-deoxy-20-(2-hydroxyethyIsulfinyl)phorboI 12,13- bis(pentafluorophenylacetate); (xvi) 20-deoxy-20-(propylsulfinyl)phorbol 12,13-bis(2',4'- difluorophenylacetate); 15 (xvii) 20-deoxy-20-(propylsulfonyl)phorbol 12,13-bis(2\4'- difluorophenylacetate); and (xviii) 20-O-(2-Hydroxyethyl)phorbol 12-Myristate 13-Acetate. 38. A compound selected from the group consisting of: 20 (i) 20-deoxy-20-(l-hydroxyethyl)phorbol 12-myristate 13-acetate; (ii) 20-deoxy-20-(2-hydroxyethyl)phorbol 12-myristate 13-acetate; (iii) 20-deoxy-20-(2-hydroxyethyl)phorbol 12,13-bis(2,4- difluorophenylacetate) 25 (iv) 12,20-dideoxy-20-(2-hydroxyethyl)phorbol 13-angelate. 39. A compound selected from the group consisting of: (i) 20-deoxy-20-(2-hydroxyethylthio)resiniferonol 9,13,14- 30 orthophenylacetate; (ii) 20-deoxy-20-(2-carboxyethylthio)resiniferonol 9,13,14- orthophenylacetate; and (iii) 20-deoxy-20-(3'hydroxypropyl)-mezerein. ) 35 40. A compound selected from the group consisting of: (i) 20-deoxy-20-(n-propylmercapto)ingenol 3-benzoate; and (ii) 20-deoxy-20-(n-propylmercapto)ingenol 3-(2',4'- difluorobenzyl)carbamate. 40 SUBSTITUTE SHEET 41. A compound selected from the group consisting of: iii) 9-Deshydroxymethyl-9-carboxyindolactam V; and iii) 9-Deshydroxymethyl-9-carboxy-epi-indolactam V. 42. A compound selected from the group consisting of: i) 14-Deshydroxy- 14-(3'-hydroxypropyl)thio-7-octyl-(9R, 12R)-indolactam V; ii) 14-Deshydroxy- 14-(4'-hydroxybutyl)thio-7-octyl-(9R,12R)-indolactam V; iii) 14-Deshydroxy- 14-trimethylphosphonium-7-octyl-(9R, 12R)-indolactam V, methanesulfonate salt; and iv) 14-Deshydroxy- 14-trimethylsilyl-7-octyl-(9R,12R)-indolactam V. 43. A compound selected from the group consisting of: i) (-)-7-Octyl- 14-deoxy- 14-(2'-hexynyl)-indolactam V; and ii) -)-7-Octyl- 14-deoxy-14-(4'-hydroxy-2'-butynylthio)-indolactam V. 44. A compound selected from the group consisting of: i) the semicarbazone of (-)-7-Octyl- 14-deoxy- 14-oxo-indolactam V; and ii) the O-methyloxime of (-)-7-Octyl- 14-deoxy- 14-oxo-indolactam V. 45. A compound selected from the group consisting of: i) (-)-7-Octylindolactam V-14-O-acetonyl ether; and ii) (-)-7-Octylindolactam V-14-O-(2'-hydroximinopropyl) ether. 46. A compound selected from the group consisting of: i) (-)-7-Octylindolactam V 14-(4'-hydroxyphenoxy)carbonate; ii) (-)-7-Octyl-14-deoxy-14-(m-hydroxymethylphenylamino)-indolactam V; iii). (-)Indolactam V 14-(4'-hydroxyphenoxy)carbonate; iv) 9-Deshydroxymethyl-9-[N-(2'-glucosyl)]-carboxamidoindolactam V; and v) 9-Deshydroxymethyl-9-[N-(2'-glucosyl)]-carboxamido-epi-indolactam V. 47. A compound comprising an antagonist of protein kinase C, a noninflammatory agonist of protein kinase C, an antagonist for toxic phorboids, or a non- inflammatory phorboid-type agonist, excluding: a) phorbol- 12-n-alkanoylesters, phorbol 12-alkenoyl esters, phorbol 12- benzoate and phorbol 12-(12'-N-dansylaminododecanoate); b) diterpene compounds in which: for all P j , S χ E j taken together, when bonded to carbon 6, are --CH3, -CH=O, -CH 2 O-R es wherein R es is an acyl group, -CH 2 O-R et wherein R et is a C j -Cg hydrocarbon radical or is — C(CH3) 2 O~linked via the oxygen atom to carbon 5 of Pi , or -CH=NNHR j1 wherein R^ is a phenyl ring with or without substituents; PιS χ Eι comprises a 12- beta-13-alpha-diacetoxy derivative of a compound having the exact 20-carbon tigliane skeleton; P j S χ E j comprises 20-deoxy- 20-chlorocrotophorbolone or 20-deoxy-20-chlorophorbol 12,13- diesters wherein the ester groups are both selected from saturated or unsaturated alkanoyl or are both benzoyl; if S X E } is =CH bonded to carbon 6 of P j , P j carries a ring formed by — OC(CH3) 2 O~ bonded in the beta configuration to carbons 3 and 4; and P j S χ E j comprises 6-deshydroxymethyl-6-carboxyphorbol 12,13-didecanoate; c) indole compounds having --COOMe, —COOEt or — CH 2 — R , in which R g is hydrogen, chloro, bromo, C1-C12 saturated or unsaturated linear or branched alkoxy, CH3OCH2O— , C j -C j ^ linear or branched alkanoyloxy, bromoacetoxy, benzoyloxy, azidobenzoyloxy, 3,5-(CH )2-CQH COO — , methanesulfonyloxy, toluenesulfonyloxy, dansyloxy, (tetrahydro-2H-pyran-2-yl)oxy, or (C j -C6 linear or branched alkyl) n (phenyl)3. n silyloxy, wherein n is 0-3, in place of the hydroxymethyl group; and d) diacylglycerol compounds having carboxyl, carbaldehyde, carbaldehyde-2,4-dinitrophenylhydrazone, cyano, alkanoyloxymethylene, alkyoxymethlene chloromethyl or methyl in place of the hydroxymethyl group. 48. A method of producing a phorboid antagonist or a non-inflammatory agonist ligand selective for one or more phorboid receptors and/or protein kinase C subtypes, comprising the step of replacing a hydroxymethyl or 1-hydroxyethyl group of a parent compound, which compound: a. binds reversibly or irreversibly to a diacylglycerol-type receptor; and/or b. activates any form of the enzyme protein kinase C; and c. contains an hydroxymethyl or 1-hydroxy-ethyl group bonded to a carbon atom; and ___. SUBSTITUTE SHEET wherein S 0 -E 0 represents a moiety which is either i) singly or doubly bonded to the carbon atom of the parent compound in place of the hydroxymethyl or 1- hydroxyethyl group; or ii) singly or doubly bonded to a carbon atom immediately adjacent to the carbon atom to which the hydroxymethyl or 1- hydroxyethyl group is bound in the parent compound; and wherein S Q is a substituted or unsubstituted, saturated, unsaturated and/or aromatic, straight or branched, acyclic, ring-containing and/or ring-carrying chain of atoms which separates P Q and E Q by a linear count of at least two but not more than 12 atoms and contains and/or carries not more than 9 heteroatoms selected from oxygen, nitrogen, silicon, sulfur, phosphorus, arsenic, boron and selenium, and not more than 16 halogen atoms; provided that the total number of atoms does not exceed 35; and wherein E Q comprises hydrogen, halogen or a saturated or singly or multiply unsaturated group containing up to 15 carbon atoms and optionally containing 1 to 12 halogen atoms and/or 1 to 6 heteroatoms selected from oxygen, nitrogen, silicon, sulfur, phosphorus, arsenic, boron and selenium, or wherein S Q E 0 taken together may be a hydrogen, halogen, thionic sulfur atom or ketonic oxygen atom or a hydroxy, amine, or thiol group singly or doubly bonded to the carbon atom of the parent compound P Q in place of the hydroxymethyl or 1-hydroxyethyl group. 4g. A composition, comprising: a physiologically acceptable pharmaceutical carrier; and a compound, in the form of an individual isomer, an isomer mixture, a racemate or optical antipode, or a pharmaceutically acceptable salt thereof, of the formula: P - G wherein P represents a radical, formally derived from a parent compound, which compound: a. binds reversibly or irreversibly to a diacylglycerol-type receptor; and/or b. activates any form of the enzyme protein kinase C; and c. contains an hydroxymethyl or 1-hydroxyethyl group bonded to a carbon atom; and wherein G is any group of 55 or fewer atoms selected from carbon, hydrogen, oxygen, nitrogen, halogen, sulfur, phosphorus, silicon, arsenic, boron and 5 selenium either i) singly or doubly bonded to the carbon atom of the parent compound in place of the hydroxymethyl or 1-hydroxyethyl group; or ii) singly or doubly bonded to a carbon atom immediately adjacent to the carbon atom to which the hydroxymethyl or 1-hydroxyethyl group is bound in the parent compound; and wherein the hydroxymethyl or 1-hydroxyethyl group of the 10 parent compound is absent or has been replaced by G. 50. A composition, comprising: a physiologically acceptable pharmaceutical carrier; and 15 a compound, in the form of an individual isomer, an isomer mixture, a racemate or optical antipode, or a pharmaceutically acceptable salt thereof, of the formula: 2 P 0 - S 0 - E 0 wherein P Q represents a radical, formally derived from a parent compound, which compound: a. binds reversibly or irreversibly to a diacylglycerol-type receptor; 25 and/or b. activates any form of the enzyme protein kinase C; and c. contains an hydroxymethyl or 1-hydroxy-ethyl group bonded to a carbon atom; and wherein S 0 -E 0 represents a moiety which is either i) singly or doubly bonded to 30 the carbon atom of the parent compound in place of the hydroxymethyl or 1- hydroxyethyl group; or ii) singly or doubly bonded to a carbon atom immediately adjacent to the carbon atom to which the hydroxymethyl or 1- hydroxyethyl group is bound in the parent compound; and 35 wherein S Q is a substituted or unsubstituted, saturated, unsaturated and/or aromatic, straight or branched, acyclic, ring-containing and/or ring-carrying chain of atoms which separates P Q and E Q by a linear count of at least two but not more than 12 atoms and contains and/or carries not more than 9 heteroatoms selected from oxygen, nitrogen, silicon, sulfur, phosphorus, 40 arsenic, boron and selenium, and not more than 16 halogen atoms; provided thatthe total number of atoms does not exceed 35; and wherein E Q comprises hydrogen, halogen or a saturated or singly or multiply unsaturated group containing up to 15 carbon atoms and optionally containing 1 to 12 halogen atoms and/or 1 to 6 heteroatoms selected from oxygen, nitrogen, silicon, sulfur, phosphorus, arsenic,boron and selenium, or wherein S Q E Q taken together may be a hydrogen, halogen, thionic sulfur atom or ketonic oxygen atom or a hydroxy, amine, or thiol group singly or doubly bonded to the carbon atom of the parent compound P Q in place of the hydroxymethyl or 1-hydroxyethyl group. 51. A composition, comprising: a physiologically acceptable pharmaceutical carrier; and a compound described in the Specification or Claim 3. 52. A composition, comprising: a physiologically acceptable pharmaceutical carrier; and a compound, or pharmaceutically acceptable salt thereof, selected from the group consisting of 6-deshydroxymethyl-6-carboxyphorbol 12,13- didecanoate; 6-deshydroxymethyl-6-carboxyphorbol 12,13-diacetate; diterpene-type phorboids with the exact 20-carbon tigliane skeleton or 19-carbon 20-nor-tigliane skeleton and acetoxy groups at positions 12- beta and 13-alpha; diterpene-type phorboids with -C^O C^^O- connecting positions 5-beta (via the oxygen atom) and 6 (via the methylene group); and diterpene-type phorboids with any of the following moieties bonded to carbon 6 of the diterpene-type phorboid: comprises a phenyl ring with or without substitution, -CH=O, --CH CI, -CH3, =CH 2 , esterified hydroxymethyl or alkyl-etherified hydroxymethyl. 53. A method for treating a mammal infected with a virus which comprises administering to a mammal in need of such treatment an antivirally effective quantity of a composition comprising an acceptable pharmaceutical carrier and an antivirally active compound or compounds, in the form of an individual isomer, an isomer mixture, a racemate or optical antipode, or a pharmaceutically acceptable salt thereof, described in the Specification or Claims hereof. 54. The method of Claim 53 wherein said disease is caused by a retrovirus. 55. The method of Claim 54 wherein said retrovirus comprises any Human Immunodeficiency Virus. 56. A method for treating a mammal infected with a virus which comprises administering to a mammal in need of such treatment an antivirally effective quantity of a composition comprising an acceptable pharmaceutical carrier and an antivirally active compound or compounds, or pharmaceutically acceptable salts thereof, selected from the group consisting of 6-deshydroxymethyl-6- carboxyphorbol 12,13-didecanoate; 6-deshydroxymethyl-6-carboxyphorbol 12,13-diacetate; diterpene-type phorboids with the exact 20-carbon tigliane skeleton and acetoxy groups at positions 12-beta and 13-alpha; diterpene-type phorboids with --C^OCfC^JgO- connecting positions 5-beta (via the oxygen atom) and 6 (via the methylene group); and diterpene-type phorboids with any of the following moieties bonded to carbon 6 of the diterpene-type phorboid: — CH=NNHR j1 wherein R j1 comprises a phenyl ring with or without substitution, ~CH=O, --CH CI, -CH3, esterified hydroxymethyl or alkyl-etherified hydroxymethyl. 57. The method of Claim 56 wherein said disease is caused by a retrovirus. 58. The method of Claim 57 wherein said retrovirus comprises any Human Immunodeficiency Virus. 59. A method of activating or inhibiting protein kinase C which comprises contacting protein kinase C or a cell containing protein kinase C with, or administering in vivo a composition containing a pharmaceutically acceptable carrier and, respectively, an activating or inhibiting amount of a compound selected from the.group in Claim 1. 60. A method of activating or inhibiting protein kinase C which comprises contacting protein kinase C or a cell containing protein kinase C with, or administering in vivo a composition containing a pharmaceutically acceptable carrier and, respectively, an activating or inhibiting amount of a compound selected from the group in Claim 2. 61. A method of activating or inhibiting protein kinase C which comprises contacting protein kinase C or a cell containing protein kinase C with, or administering in vivo a composition containing a pharmaceutically acceptable carrier and, respectively, an activating or inhibiting amount of a compound described in the specification or selected from the group in Claim 3. sun STITUTE SHEET

Inventors: DRIEDGER PAUL E, QUICK JAMES, DRIEDGER, PAUL, E., QUICK, JAMES
Applicants: ALDER RES CENTER LTD, ALDER RESEARCH CENTER LIMITED PARTNERSHIP
Application year: 1991
Main classification: C07C69
IPC codes: A61K31, A61P31, C07C69, C07C225, C07C247, C07C255, C07C275, C07C309, C07C317, C07C323, C07C333, C07D209, C07D213, C07D401, C07D403, C07D487, C07D521, C07F7, C07F9, C07H13