NEW CEPHALOTAXANES, THEIR METHOD OF PREPARATION AND THEIR USE IN TREATMENT OF CANCERS, LEUKEMIAS, PARASITES INCLUDING THUS RESISTANT TO USUAL CHEMOTHERAPEUTIC AGENTS AND AS REVERSAL AGENTS

Abstract: The present invention concerns a compound of formula (I) wherein: W represents O or NH, Q represents an unbranched or branched, saturated or unsaturated or aromatic, cyclic or acyclic or heterocyclic hydrocarboned radical containing 1 to 30 carbon atoms including or not heteroatom(s), R<1> is H, OH, OMe, O-(C1-C30)-alkyl, O-aryl-(C1-C30)-alkyl, O-(C2-C30)-alkenyl, O-(C3-C30)-cycloalkyl or null and R<2> is H or OH, or R<1>, R<2> form together -O-, R<3>=R<4>=OMe or R<3> and R<4> form together -OCH2O-, R is H, C1-C30alkyl or O-protecting group and R<6> represents an unbranched or branched, saturated or unsaturated or aromatic, cyclic or acyclic or heterocyclic hydrocarboned radical containing 1 to 30 carbon atoms including or not heteroatom(s), or R and R<6> form together -CMe2-, n is 0 to 8, R<5> is H, OH, OMe, O-(C1-C30)-alkyl, O-aryl-(C1-C30)-alkyl, O-(C2-C30)-alkenyl, O-(C3-C30)-cycloalkyl or O-aryl, the doted line is null or forms a double bond depending on the meaning of R<1>. It also concerns their methods of preparation and their use in treatment of cancers, leukemias, parasites and as reversal agents of harringtonines.

Description: TITLE NEW CEPHALOTAXANES, THEIR METHOD OF PREPARATION AND THEIR USE IN TREATMENT OF CANCERS, LEUKEMIAS, PARASITES INCLUDING THUS RESISTANT TO USUAL CHEMOTHERAPEUTIC AGENTS AND AS REVERSAL AGENTS The present invention concerns new cephalotaxanes, their methods of preparation and their use in treatment of cancers, leukemias, parasites including thus resistant to usual chemotherapeutic agents and as reversal agents of harπngtonines Cephalotaxanes (CTX) are particular alkaloids today only extracted from the Cephalotaxaceae family which exhibiting the structural formula 1 1 Several substituents may be encountered on this core hydroxyl, ether, acyloxy etc Some double bound or intramolecular bridge achieve to definite cephalotaxanes Several dozen of cephalotaxanes have been isolated from various cephalotaxus species Cephalotaxoids include cephalotaxanes and unnatural analogs of cephalotaxanes Cephalotaxines 2 are cephalotaxanes without acyloxy side-chain Harπngtonines (i e harπngtonine = HA and homoharπngtomne = HHT) are natural esters of cephalotaxines exhibiting generally a strong cytotoxic activity Harπngtonines are natural esters of cephalotaxines exhibiting generally a strong cytotoxic activity Harπngtoids include harπngtonines and unnatural analogs of harπngtonines Two harπngtonines are very promising drugs in the treatment of certain leukemia such as Chronic Myelogenous Leukemia (CML) Definite activity of HHT was observed in acute myelogenous leukemia (AML) acute promyeiocytic leukemia (APL), and myelodysplastic syndrome (MDS) (Warrell Jr Rpet al 3 617- 621 , 1985, Feldman E et al, Leukemia 6 1185-88, 1992, Feldman EJ et al, Leukemia 10 40-42, 1996, Kantarjian H et al , Cancer 63 813-817, 1989 Kantarjian H et al , J Clin Oncol 18 3513-3521 ,2000) The present applicant have initiated in France compassionate use of HHT in CML patients resistant or not eligible to all existing therapies and several phase II and III clinical trials including in patient with CML and AML are ongoing in France and in the U S However it should be pointed out that harπngtonines pertain to the series of natural drugs exhibiting the multiresistance phenomenon which led to relapse of the cancer diseases This situation is a serious limitation to the use of natural chemotherapeutic agents in the treatment of cancers and leukemia Harπngtonine inhibit protein synthesis at the level of elongation, however ultimate mechanism of action of harπngtonine remain unknown The final result is the self-destruct of the cell Clinically, harπngtonines have a selective action in leukemia of the myeloid series In addition harπngtonines interacts with P Glycoprotein (PGP) and Multiresistance Protein (MRP) PGP MRP and other efflux pumps are complex molecular entities which are ubiquist in nature Their role is to selectively efflux the environmental natural toxic agents, including agents of chemotherapy (anthracyclines, taxanes, epipodophyllotoxins, harπngtonine, etc ) It was pointed out that no common structural feature of this natural cytotoxic may related to molecular recognizing by PGP A number of analogs all less active than harπngtonines have been synthesized The more active among these esters are about one magnitude less cytotoxic than harπngtonines in vitro (i e HA, HHT neoharπngtonine, have an activity = IC50 ranged from 10 to 30 ng per mL whereas analog previously synthesized have an IC50 higher than 100ng/mL) No relation structure activity relationship had been previously found since the discovering of harπngtonines Therefore, there is the need of new analogs of harπngtonines having the same magnitude of cytotoxicity than harπngtonines in vitro Surprisingly, the present applicant have synthesized a series of CTX analogs exhibiting stronger in vitro inhibition of leukemic cell lines such as K562 than HHT used as reference The present invention provides cephalotaxanes having formula (I) wherein W represents O or NH Q represents an unbranched or branched, saturated or unsaturated or aromatic, cyclic or acyclic or heterocyclic hydrocarboned radical containing 1 to 30 carbon atoms including or not heteroatom(s), R is H, OH, OMe, O-(C 1 -C 30 )alkyl, O-aryl(C 1 -C 30 )alkyl, O-(C 2 -C 30 )alkenyl, O-(C 3 -C 30 )cycloalkyl or null and R 2 is H or OH, or R , R 2 form together -0-, R 3 = R 4 = OMe or R 3 and R 4 form together -OCH 2 0-, R is H, Cι-C 30 alkyl or O-protecting group and R 6 represents an unbranched or branched, saturated or unsaturated or aromatic, cyclic or acyclic or heterocyclic hydrocarboned radical containing 1 to 30 carbon atoms including or not heteroatom(s), or R and R 6 form together -CMe 2 -, n is 0 to 8, R 5 is H, OH, OMe, O-(C 1 -C 30 )alkyI, O-aryl(C 1 -C 30 )alkyl, O-(C 2 -C 30 )alkenyl, O-(C 3 -C 30 )cycloalkyl or O-aryl, • the doted line is null or forms a double bond depending on the meaning of R\ except for compounds where • W represents O, the doted line forms a double bond, R is null, R 2 is H, R 3 and R 4 represent -O-CH 2 -O-, R 5 is OMe, Q = C0 2 R 7 and 1 °) R = H, R 6 = -(C-OH)Me 2 , n = 2 or 3, R 7 = Me or H, 2°) R = H, R B = -(C-H)Me 2 , n = 2 to 4, R 7 = Me, 3°) R = H, R e = -(C-H)Me 2l n = 1 or 2, R 7 = H, 4°) R = H, R 5 = Ph, n = 1 to 3, R 7 = Me, 5°) R = H, R 6 = -CH=CH-Ph, n = 0, R 7 = Me, 6°) R = H, R 5 = CH 3l n = 4, R 7 = Me, 7°) R and R 6 form together -CMe2-, n = 2 or 3, R 7 = Me, • W represents O, the doted line forms a double bond, R 1 is null, R 2 is OH, R 3 and R 4 represent -0-CH2-0-, R 5 is OMe and R = H, R 6 = -(C-H)Me 2l n = 2 or 3, R 7 = Me • W represents O, the doted line is null, R 1 and R 2 represent -0-, R 3 and R 4 represent -O-CH 2 -0-, R 5 is OMe and R = H, R 6 = -(C-H)Me 2 , n = 2, R 7 = Me The term "O-Protecting group" as used in the present invention refers to a substituent which protects hydroxyl groups against undesirable reactions during synthetic procedures such as those O-protecting groups disclosed in Greene, "Protective Groups In Organic synthesis", (John Wiley & Sons, New York (1981 )) O-protecting groups comprise substituted methyl ethers, for example, methoxymethyl, benzyloxymethyl, 2-methoxyethoxymethyl, 2-(trιmethylsιlyl) ethoxymethyl, t-butyl, benzyl and tπphenylmethyl, tetrahydropyranyl ethers, substituted ethyl ethers, for example 2,2,2-trιchloroethyl, silyl ethers, for example, trimethylsilyl, t-butyldimethylsilyl and t-butyldiphenylsilyl and esters prepared by reacting the hydroxyl group with a carboxylic acid for example, acetate, propionate, benzoate and the like The term "C-|-C 30 alkyl" as used in the present invention refers to straight or branched chain substituted or unsubstituted alkyl radicals containing from 1 to 30 carbon atoms including, but not limited to, methyl, ethyl, n-propyl, iso-propyl, n- butyl, iso-butyl, sec-butyl, t-butyl, n-pentyl, n-hexyl and the like The term "C 2 -C 30 alkenyl ' as used in the present invention refers to straight or branched chain substituted or unsubstituted alkenyl radicals containing from 1 to 30 carbon atoms including, but not limited to, ethenyl, propenyl, butenyl, pentenyl, hexenyl and the like. The term "aryl ' as used in the present invention refers to a monocyclic or bicyclic carbocyclic ring system having one or more aromatic rings including but not limited to, phenyl, naphthyl, tetrahydronaphthyl, indanyl and the like. Aryl groups can be unsubstituted or substituted with one or more substituents. The term "aryl(C-rC 30 )alkyl" as used in the present invention refers to an aryl group such as defined above appended to a CrCgoalkyl radical such as defined above, for example, benzyl and the like. The term "C 3 -C 30 cycloalkyl" as used herein refers to a carbocyclic ring having 3 to 30 carbon atoms including, but not limited to, cyclopropyl, cyclopentyl, cyclohexyl and the like. Cycloalkyl groups can be unsubstituted or substituted with one or more substituents. An advantageous embodiment provides compounds of formula (I) wherein Q = COZ-R 8 , • Z = O, S, or NH, and or Z-R 8 is NR 2 R 13 , R 12 and R 3 representing respectively R 9 and R 10 , R 9 , R 0 , R 11 are independently H, C C 30 alkyl, C 3 -C 30 cycloalkyl, aryl, aryl-(d- C 30 )-alkyl, C 2 -C 30 alkenyl, C 2 -C 30 alkynyl, Cι-C 30 trihalogenoalkyl, C C 30 alkylamino- (C 1l -C 30 )-alkyl, C -C 30 dialkylamϊno-(C 1 -C 3 o)-alkyl, or amino-(C 1 -C 30 )-alkyl, or where R 4 , R S , R 16 are independently H, halogen, C,-C 30 alkyl, C 3 -C 30 cycloalkyl, aryl, aryl-(C 1 -C 30 )-alkyl, C 2 -C 30 alkenyl or C 2 -C 30 alkynyl, Cι-C 30 trϊhalogenoalkyl, m is 0 to 4, each of these groups including or not heteroatom(s), such as in particular S, N or O. The term "C 2 -C 30 alkynyl" as used in the present invention refers to straight or branched chain substituted or unsubstituted alkynyl radicals containing from 1 to 30 carbon atoms including, but not limited to, ethynyl, propynyl, butynyl, pentynyl, hexynyl, heptynyl and the like The term "Cι-C 30 trιhalogenoalkyl" as used in the present invention refers to straight or branched chain alkyl radicals containing from 1 to 30 carbon atoms substituted by three halogen atoms The term "C C 3 oalkylamιno" as used in the present invention refers to R 18 NH- wherein R 18 is a C C 30 alkyl group such as defined above The term "C C 30 dιalkylamιno" as used herein refers to R 19 R 20 N- wherein R 19 and R 20 are independently selected from C-pdoalkyl such as defined above The term "CrCsoaminoalkyl' as used herein refers to a CrC 30 alkyl radical such as defined above to which is appended an ammo group (-NH 2 ) The term "C 1 -C 30 alkylamιno-(Cι-C 30 )-alkyl" as used herein refers to a C C 30 alkyl radical such as defined above to which is appended an Cι-C 30 alkylamιno group such as defined above The term "C 1 -C 3 odιalkylamιno-(C 1 -C 30 )-alky ' as used herein refers to a Cι- C 30 alkyl radical such as defined above to which is appended an d- C 30 dιalky!amιno group such as defined above Another advantageous embodiment provides compounds of formula (I) wherein • R 6 = -(C-Y)Me 2 , -CH=CMe 2 , or an aryl group or R and R δ form together -CMe 2 -, Y = H OH or halogen A further advantageous embodiment provides compounds of formula (I) wherein the doted line forms a double bond R 1 is null R 2 ιs H R 3 and R 4 represent -0-CH 2 -0- A further aspect of the invention provides compounds of formula (I) wherein • the doted line is null • R 1 and R 2 represent -O- R 3 and R 4 represent -0-CH 2 -0- R 5 is OMe. Yet, a further preferred embodiment provides compounds of formula (I) wherein n = 1 to 3. Another further aspect of the invention provides compounds of formula (I) wherein W represents O. Advantageously, a compound according to the present invention is selected from the group consisting of the following compounds 1 to 65 : 2 10 11 12 13 14 15 16 17 18 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 and 65. Th advantageous compounds of the present invention are the one of formula (I) wherein Q represents COZR 8 , Z is such as described above and R 8 has 6 carbon atoms without any hydrophilic group. Some of the compounds described herein contain one or more centers of asymmetry and may thus give rise to diastereoisomers and optical isomers. The present invention is meant to comprehend such possible isomers or diastereoϊsomers alone or in a mixture, such as for example their racemic mixture. Some of the compounds described herein contain olefinic double bonds and are meant to include both E and Z geometric isomers. Another aspect of the invention is a process for preparing a compound of formula (I). A, In the case where W represents NH, it comprises the following steps A1 to A2: A1 : reacting cephalotaxines of formula V : wherein R is H, OH, OMe, O-(C 1 -C 30 )alkyl, O-aryl(C 1l -C 30 )alkyl, O-(C 2 -C 30 )alkenyl, O-(C 3 -C 30 )cycloalkyl or null and R 2 is H or OH, or R 1 , R 2 form together -0-, R 3 = R 4 = OMe or R 3 and R 4 form together -OCH 2 0-, R 5 is H, OH, OMe, ©-(C-rCao kyl, O-aryl(C C 30 )alkyl, O-(C 2 -C 30 )alkenyl, O-(C 3 -C 30 )cycloalkyl or O-aryl, • the doted line is null or forms a double bond depending on the meaning of R 1 by methods known by the one skilled in the art to obtain the compounds of formula VI wherein R 1 is H, OH, OMe, O-(C 1 -C 30 )alkyl, O-ary d-C^alkyl, O-(C 2 -C 30 )alkenyl, O-(C 3 -C 30 )cycloalkyl or null and R 2 is H or OH, or R 1 , R 2 form together -O-, R 3 = R 4 = OMe or R 3 and R 4 form together -OCH 2 0-, • R 5 is H, OH, OMe, O-(C 1 -C 30 )alkyl, O-aryl(C r C 30 )alkyl, O-(C 2 -C 30 )alkenyl, O-(C 3 -C 30 )cycloalkyl or O-aryl, • the doted line is null or forms a double bond depending on the meaning of R 1 For example, such methods are the following : - substituting the hydroxyl group of the cephalotaxines of formula V by an halogen or a tosylate by methods known by the one skilled in the art (such as by using SOCl 2 ), then substituting the halogen or the tosylate by the group NH 2 by methods known by the one skilled in the art (such as 1 ) the use of gaseous ammoniac in methylene chloride at 0°C and 1 atm or 2) the use of NaN 3 in DMF followed by 2f) a catalytic hydogenolysis with for example Pd/C as the catalyst or 2 2 ) the use of LiAlH 4 ) to obtain the compounds of formula VI. A2 : reacting the compounds of formula VI by the methods disclosed in WO 99/48894. B. In the case where W represents O, Q = COR 8 and R 8 is such as described above, it comprises the step of reacting harringtonines or homoharringtonines commercially available (by SIGMA) with organometallic compounds, advantageously organolithium or grignard reagent. C. In the case where W represents O, Q=CH 2 ZR 8 or CH 2 R 8 and Z and R 8 are such as described above, it comprises the step of reducing harringtonines or homoharringtonines commercially available (by SIGMA) with an hydride, advantageously boron or aluminium hydride D. In the case where W represents O, Q = COZ-R 8 and Z and R 8 are such as described above, it comprises the following steps ϊ) then ΪI), i) hydrolyzing selectively the compound of formula (IV) which is available commercially wherein R is H, OH, OMe, O^d-C^-alkyl, O-aryl -(C^C^-alkyl, O-(C 2 -C 30 )- alkenyl, O-(C 3 -C 30 )-cyc!oalkyl or null and R 2 is H or OH, or R and R 2 form together -O- R 3 = R 4 = OMe or R 3 and R 4 form together -OCH 2 0- • R is H, d-doalkyl or O-protecting group and R 6 represents an unbranched or branched, saturated or unsaturated or aromatic, cyclic or acyclic or heterocyclic hydrocarboned radical containing 1 to 30 carbon atoms, including or not heteroatom(s), or R and R 6 form together -CMe 2 - • n is 0 to 8. R 5 is H, OH, OMe, O-(C 1l -C 30 )-alkyl, O-aryl-(C 1 -C 30 )-alkyl, O-(C 2 -C 30 )-alkenyl, O-(C 3 -C 30 )-cycloalkyl or O-aryl. • the doted line is null or forms a double bond depending on the meaning of R 1 , with an agent such as mineral hydroxide, advantageously lithium, potassium or sodium hydroxide, in hydro-organic solvent mixture to give as reaction product, amphoteric acid of formula (III) wherein R 1 to R 5 , R and R 6 are defined as above, ii) performing the esterification of the above obtained amphoteric acid of formula (III) with an esterification agent and a compound of formula R 8 -ZH, R 8 and Z being defined as above and wherein the steps i) and ii) are carried out successively or simultaneously. Advantageously the compounds of the following formula wherein R 1 ' is H, OH, OMe, O-(C 1l -C 30 )-alkyl, O-aryl -(C 1 -C 30 )-alkyl, O-(C 2 -C 30 )- alkenyl, O-(C 3 -C 30 )-cycloalkyl or null and R 2 is H or OH, or R 1 ' and R 2 form together -O- R 3 = R 4 = OMe or R 3 and R 4 form together -OCH 2 0- R is H, d-doalkyl or O-protecting group and R 6 represents an unbranched or branched, saturated or unsaturated or aromatic, cyclic or acyclic or heterocyclic hydrocarboned radical containing 1 to 30 carbon atoms including or not heteroatom(s), or R and R 6 form together -CMe 2 - • n is 0 to 8 R 5 is H, OH, OMe, O-(C C 30 )-alkyl, O-aryKd-C^-alkyl, O-(C 2 -C 30 )-alkenyl O-(C 3 -C 30 )-cycloalkyl or O-aryl • the doted line is null or forms a double bond depending on the meaning of R\ • Z = O or S, and • R 17 represents C C 30 alkyl, C 2 -C 30 alkenyl C 3 -C 30 cycloalkyl, C 2 -C 30 alkynyl, aryl- (C C 30 )-alkyl or aryl and advantageously methyl or ethyl, can also be used instead of the compounds of formula IV to prepare, according to the process A, the product of formula (I) Advantageously, the esterification agent in process A is a lewis acid or a protonic acid In an advantageous embodiment of the process A according to the present invention, the amphoteric acid of formula (III) is activated with an imide or by formation of a mixte anhydride or an acid chloride Advantageously the imide is dicyclohexylcarbodiimide or diisopropylcarbodiimide More advantageously the mixte anhydride is formed with 2 4,6- tπchlorobenzoic acid by contact with 2,4,6-trιchlorobenzoyl chloride in the presence of a base In another advantageous embodiment of the process A according to the present invention, the steps i) and n) are carried out simultaneously, without isolation of the amphoteric acid of formula (III), via a reaction of transestenfication performed in presence of an acidic or basic catalyst Advantageously, the catalyst is a base, such as an alkaline hydride More advantageously the catalyst is a lewis acid or a protonic acid Given their pharmacological properties, the compounds of the present invention may be used in human therapy in the treatment of cancer pathology This invention includes also a pharmaceutical composition which comprises a therapeutically effective amount of at least one compound according to the present invention with one or more pharmaceutically acceptable carriers excipients or diluents These pharmaceutical compositions may be formulated for oral, intravenous or subcutaneous administration Another aspect of the invention is the use of at least one compound according to the present invention or of the pharmaceutical composition as described above as (i) chemotherapeutic agent, (n) enhancer of other chemotherapeutic agents (in) for inhibiting tumors growth, (iv) for inhibiting mammalian parasites, Yet, another aspect of the invention is the use of at least one compound according to the present invention for the preparation of a pharmaceutical composition as (i) chemotherapeutic agent, ( ) enhancer of other chemotherapeutic agents (in) for inhibiting tumors growth, (iv) for inhibiting mammalian parasites or (v) as reversal agents in particular of harringtonines (a reversal agent is an agent able to reverse the cell multiresistance phenomenon) Finally, the present invention describes a method for treating mammalian tumors which comprises administering to a mammal a therapeutically effective amount of at least one compound according to the present invention Another advantages of the compounds according to the present invention, is its activity on leukemic cell lines exhibiting resistance to other agents including harringtonines The following examples which are given without implied limitation, illustrates the present invention Example 1 Preparation of (-)-cephalotaxyl (2'S)-2~carboxymethyl-6,6-dιmethyl-2- tetrahydropyranecarboxylate or 4 -demethyl-anhydro-ep homohai rinqtonine To a stirred solution of anhydro-epi-homoharπngtonine (5 g, 9 48 mmol) in ethanol (162 5 ml) was added potassium hydroxide (5 35mg, 94 8 mmol) and water (50 ml) After stirring 7 hours at ambient temperature and evaporation of ethanol under reduced pressure, the residual aqueous layer is saturated with sodium chloride and extracted with dichloromethane (3 x 100 ml) The combined organic layers were dried over magnesium sulfate, and evaporated to dryness The resulting crude product was purified by column chromatography (silica 15-40 μm (50g), dichloromethane then dichloromethane / methanol, 90 10 to 75 25) to provide the expected compound (4 6g, 95%) The product thus obtained showed the following characteristics 1 H NMR 400 MHz (CDCl 3 ) (δ ppm, J Hz) 6 61 (1 H, s, H-14 λ ), 6 58 (1 H, s, H-17*), 5 85 (3H, m, H-3 + OCH 2 0), 5 06 (1 H, s, H-1 ), 3 80 (1 H, d, J 4 . 3 = 9 6, H-4), 3 68 (3H, s, OCH 3 ), 3 09 (2H, m, H-1 1 β + H- 8α), 2 94 (1 H, m, H-10α), 2 60 (2H, m, H-8β + H-10β), 2 37 (1 H, dd, J AB = 14 0, J = 6 7, H-1 1 σ), 2 16 and 1 90 (2H, 2d, J AB = 12 3, CH 2 C0 2 ), 2 02 (I H, m, H-6 A ), 1 90 (1 H, m H-6 B ), 1 76 (2H m, CH 2 -7) 1 5 - 1 2 (6H, m, 3 χ CH 2 ), 1 26 (3H s, CH 3 ), 1 05 (3H, s, CH 3 ) Example 2 Preparation of (-)-cephalotaxyl (2'R)-2-carboxymethyl-6,6-dimethyl~2~ tetrahydropyrane carboxylate or 4'-demethyl-anhydro-homoharrιnqlonιne To a stirred solution of anhydro-homoharπngtonine (1g, 1 9 mmol) in ethanol (32 5 ml) was added potassium hydroxide (1 ,07g, 19 mmol) and water (10 ml) After stirring 6 hours at ambient temperature and evaporation of ethanol under reduced pressure, the residual aqueous layer is saturated with sodium chloride and extracted with dichloromethane (3 x 25 ml) The combined organic layers were dried over magnesium sulfate, and evaporated to dryness The resulting crude product was purified by column chromatography (silica 15-40 μm (10g), dichloromethane then dichloromethane / methanol, 98 2 to 80 20) to provide the expected compound (678 mg, 69 5%) The product thus obtained showed the following characteristics 1 H NMR 400 MHz (CDCI 3 ) (δ ppm, J Hz) 6 64 (1 H, s, H-17), 6 56 (1 H, s, H-14), 5 90 (3H, br s, H-3 + OCH 2 0) 5 07 (1 H s H-1 ), 3 80 (1 H, d, J 4 . 3 = 9 6, H-4), 3 71 (3H, s, OCH 3 ), 3 09 (2H, m, H-11 β+ H-8 ), 2 95 (1 H, dd, J AB = 11 6, J = 6 9, H-10α), 2 59 (2H, m, H-8β + H-10β), 2 37 (1 H, dd, J AB = 14 0, J = 6 7, H-1 1 α), 2 07 and 2 02 (2H, 2d, J AB = 9 6, CH 2 C0 2 ), 1 91 (1 H, m, H-6 A ), 1 75 (3H m, H-6 B + CH 2 -7), 1 6 - 1 0 (6H, m, χ CH 2 ), 1 22 (3H, s, CH 3 ), 1 09 (3H, s, CH 3 ) Example 3 Preparation ofX-cephalotaxyl (2'S)-2-ethoxycarbonylmethyl-6,6-dimethyl-2- tetrahydropyrane carboxylate or 4'-ethyl-4 -demethyl-anhydro-epi- homohamnqtonine 1°) Method A A mixture of 4'-demethyl-anhydro-epι-homoharnngtonιne resulting from Example 1 (100 mg, 0 195 mmol) and a solution of boron trifluonde-etherate in ethanol 1 5 M (1 12 ml, 0 973 mmol) was stirred at ambient temperature for 15 hours and at 50°C for 5 hours After cooling of the reaction mixture, sodium hydroxide 2N was added to pH 10 and the resulting layer was extracted with dichloromethane (3 x 10 ml) The combined organic layers were washed with brine (50 ml), dried over magnesium sulfate and evaporated to dryness to provide the expected compound (80 mg crude, 76%) The crude product thus obtained showed the following characteristics 1 H NMR 400 MHz (CDCI 3 ) (δ ppm, J Hz) 662 (1H, s, H-14*), 658 (1H, s, H-17*), 585 (3H. m, H-3 + OCH 2 0), 502 (1H, s, H-1), 405 (2H, m, 0CH 2 CH 3 ), 379 (1H, d, J 43 = 96, H-4), 365 (3H s, OCH 3 ), 326 (1H, m, H-11β), 313 (1H, m, H-8α), 299 (1H, m, H-10α), 266 (2H, m, H-8β + H-10β), 243 (1H, dd, JAB = 145, J = 67, H-11α), 212 and 178 (2H, 2d, J AB = 142, CH 2 C02), 204 (1H, m, H-6 A ), 188 (1H, m, H-6 B ), 178 (2H, m, CH 2 -7), 15 - 09 (6H, m, 3 χ CH 2 ), 122 (3H, t, J = 72, OCH 2 CH 3 ), 116 (3H, s, CH3), 102 (3H, s, CH 3 ) 2°) Method B Sodium hydride 60% (0.5 mg, 0 037 mmol) was added to a solution of anhydro-epi-homoharπngtonine (39 mg 0.074 mmol) resulting from Example 1 in dry ethanol (1 ml) and the resulting mixture was stirred at ambient temperature for 48 hours After addition of water (5 ml) the resulting aqueous layer was extracted with ether (2 x 5 ml) The combined organic layers were washed with brine (2 x 100 ml) dried over magnesium sulfate and evaporated to dryness to provide the expected product (24 mg crude, 60%) The product thus obtained showed identical characteristics to this obtained with method A 3°) Method C To a stirred mixture of 4'-demethyl-anhydro-epι-homoharrιngtonιne (50 mg, 0097 mmol) resulting from Example 1 in dry dichloromethane (0 35 ml) was added at 0°C triethylamine (dried over potassium hydroxide) (13 μl, 0 097 mmol) and 2,4,6-trιchlorobenzoyl chloride (15 μl, 0 097 mmol) over a period of 10 minutes After stirring at ambient temperature for 2 hours a solution of 4- dimethylaminopyridine (23 8 mg, 0 195 mmol) and ethanol (10 μl, 0 175 mmol) in dry dichloromethane (0 15 ml) was added After stirring at ambient temperature for 2 5 hours, the reaction mixture was diluted with dichloromethane (5 ml) The resulting organic layer was successively washed with water (5 ml), with saturated sodium hydrogen carbonate solution (5 ml), with brine (5 ml) The resulting aqueous layer was extracted with dichloromethane (10 ml), then the combined organic layers after drying over magnesium sulfate were evaporated to dryness The resulting crude product thus obtained (44 mg crude, 85%) showed identical characteristics to this obtained with method A Example 4 Preparation of (-)-cephalotaxyl (2'R)-2-ethoxycarbonylmethyl-6,6-dιmethyl-2- tetrahydropyrane carboxylate or 4'-ethyl~4'-demethyl-anhvdro-homohamnqtonιne To a stirred mixture of 4 -demethyl-anhydro-homoharπngtonine (256 mg 0 498 mmol) resulting from Example 2 in dry dichloromethane (1 8 ml) was added at 0°C triethylamine (dried over potassium hydroxide) (69 μl 0 498 mmol) and 2,4,6-trιchlorobenzoyl chloride (78 μl, 0 498 mmol) over a period of 10 minutes After stirring at ambient temperature for 2 5 hours a solution of 4- dimethylaminopyπdine (121 mg, 0 996 mmol) and ethanol (58 μl, 0 996 mmol) in dry dichloromethane (0.8 ml) was added After stirring at ambient temperature for 15 hours, the reaction mixture was diluted with dichloromethane (5 ml) The resulting organic layer was successively washed with water (7 ml), with saturated sodium hydrogen carbonate solution (7 ml), with brine (5 ml) After a last extraction of the combined aqueous layers with dichloromethane (10 ml) the combined organic layers were dried over magnesium sulfate and evaporated to dryness The resulting crude product was purified by column chromatography (silica 15-40 μm (8g), dichloromethane then dichloromethane / methanol, 99 1 to 97 3) to provide the expected compound (241 mg, 89%) The product thus obtained showed the following characteristics IR (film ) (cm-1) 1735 (C02), 1657 (C=C-0), 1504 (Ar), 1221 (C-O), 1 141 (C-O), 1080 (C-O), 1034 (C-O), 930 1 H NMR 400 MHz (CDCI 3 ) (δ ppm, J Hz) 6 62 (1 H, s, H-14*), 6 58 (1 H, s, H-17*), 5 92 (1 H, d, J 3 4 = 9 5, H-3), 5 89 and 5 81 (2H, 2s, OCH 2 0), 5 06 (1 H, s, H-1 ), 4 06 (2H ( m, OCH 2 CH 3 ), 3 78 (1 H, d, H- 4), 3 72 (3H, s, OCH 3 ), 3 20 (2H, m, H-1 1 β + H-8α), 3 01 (1 H, m, H-1 Oo), 2 67 (2H, m, H-8β + H-10β), 2 41 (1 H, m, H-1 1 σ), 2 14 and 1 66 (2H, 2d, JAB = 14 4, CH 2 C0 2 ), 2 06 (1 H, m, H-6 A ), 1 80 (1 H, m, H-6 B ), 1 68 (2H, m, CH 2 -7), 1 65 - 1 2 (6H, m, 3 χ CH 2 ), 1 21 (3H, t, J = 7 1 , OCH 2 CH 3 ), 1 10 (3H, s, CH 3 ), 1 01 (3H, s, CH 3 ) Example 5 Preparation of (-)-cephalotaxyl (2'S)-2-isopropyloxycarbonylmethyl-6,6-dimethyl- 2-tetrahydropyrane carboxylate or 40sopropyl-4'-demethyl-anhydro-epi- homohamnqtonine A mixture of 4'-demethyl-anhydro-epi-homoharringtonine resulting from Example 1 (100 mg, 0.195 mmol) and a solution of boron trifluoride-etherate in isopropanol 6 M (1.5 ml, 3.9 mmol) was stirred at ambient temperature for 15 hours. The reaction mixture was alkalinized to pH 10 with sodium hydroxide 2N (6 ml) and the resulting layer was extracted with dichloromethane (3 x 10 ml). The combined organic layers were washed with brine (10 ml), dried over magnesium sulfate and evaporated to dryness. The resulting crude product was purified by column chromatography (silica 15-40 μm (2.4g), dichloromethane then dichloromethane / methanol, 99:1 ) to provide the expected compound (56 mg, 52%). %). The product thus obtained showed the following characteristics: 1 H NMR 400 MHz (CDCI 3 ) (δ ppm, J Hz): 6.61 (1 H, s, H-14*), 6.58 (1 H, s, H-17*), 5.84 (3H, m, H-3 + OCH 2 0), 5.02 (1 H, s, H-1 ), 4,92 (1 H, m, J = 6.2, CH(CH 3 ) 2 ), 3,78 (1 H, d, J 4 . 3 = 9.6, H-4), 3.65 (3H, s, OCH 3 ), 3.24 (1 H, m, H-11 β), 3.09 (1 H, m, H-8α), 2.94 (1 H, m, H-10α), 2.60 (2H, m, H-8β + H-10β), 2.40 (1 H, dd, JAB = 14.4, J = 6.6, H-11α), 2.08 and 1.71 (2H, 2d, J AB = 13.8, CH 2 C0 2 ), 2.01 (1 H, m, H-6 A ), 1.9 - 1.0 (6H, m, 3 χ CH 2 ), 1.86 (1 H, m, H-6 B ), 1.75 (2H, m, CH 2 -7), 1.20 (6H, d, J = 6.2, CH(CH 3 ) 2 ), 1.12 (3H, s, CH 3 ), 101 (3H. s, CH 3 ). Example 6 Preparation of(-)-cephalotaxyl (2'R)-2-isopropyloxycarbonylmethyl-6,6-dimethyl-2- tetrahydropyrane carboxylate or 4øsopropyl-4'-demethyl-anhydro- homoharrinqtonine : To a stirred mixture of 4'-demethyl-anhydro-homoharrιngtonιne (255 mg, 0 498 mmol) resulting from Example 2 in dry dichloromethane (1 8 ml) as added at 0°C triethylamine (dried over potassium hydroxide) (69 μl, 0 498 mmol) and 2,4,6-tπchlorobenzoyl chloride (78 μl, 0 498 mmol) over a period of 10 minutes After stirring at ambient temperature for 2 5 hours a solution of 4- dimethylaminopyπdine (121 mg, 0 996 mmol) and isopropanol (76 μl, 0 996 mmol) in dry dichloromethane (0 8 ml) was added After stirring at ambient temperature for 15 hours, the reaction mixture was diluted with dichloromethane (5 ml) The resulting organic layer was successively washed with water (7 ml), with saturated sodium hydrogen carbonate solution (7 ml), with brine (7 ml) The resulting aqueous layer was extracted with dichloromethane (10 ml), then the combined organic layers after drying over magnesium sulfate were evaporated to dryness The resulting crude product was purified by column chromatography (silica 15-40 μm (8), dichloromethane then dichloromethane / methanol, 99 1 to 98 2) to provide the expected compound (216 mg 78%) The product thus obtained showed the following characteristics IR (film ) (cm "1 ) 1731 (C0 2 ), 1656 (C=C-O), 1504 (Ar), 1223 (C-O), 1 142 (C-O), 1 108 (C-O) 1036 (C-O), 914 1 H NMR 400 MHz (CDCl 3 ) (δ ppm, J Hz) 6 62 (1 H s H-14*), 6 59 (1 H, s, H-17*) 5 91 (1 H d, J 3 . 4 = 9 6, H-3), 5 88 and 5 79 (2H 2s, OCH 2 0) 5 04 (1 H s, H-1 ) 4 93 (1 H, m J = 6 3 CH(CH 3 ) 2 ) 3 79 (1 H d J 4 . 3 = 9 3, H-4) 3 72 (3H s OCH 3 ) 3 19 (2H m, H-11 J} + H-8α) 2 99 (1 H m H-10α) 2 62 (2H m, H-8β + H-10β) 2 41 (1 H m H-11α) 2 09 and 1 70 (2H, 2d, J AB = 14 1 CH 2 C02), 2 04 (1 H, m H-6 A ) 1 91 (1 H m H-6 B ) 1 77 (2H m CH 2 -7), 1 65 - 1 2 (6H, m, 3 χ CH 2 ), 1 19 (6H, d J 6 3 CH(CH 3 ) 2 ) 1 1 1 (3H s, CH 3 ), 1 02 (3H, s, CH 3 ) Example 7 Preparation of (-)-cephalotaxyl (2'S)-2-benzyloxycarbonylmethyl-6,6-dιmethyl-2- tetrahydropyrane carboxylate or 4'-benzyl-4'-demethyl-anhydro-epι- homoharnnqtonine To a stirred mixture of 4'-demethyl-anhydro-epι-homoharrιngtonιne (62 mg, 0 12 mmol) resulting from Example 1 in dry dichloromethane (0 43 ml) was added at 0°C triethylamine (dried over potassium hydroxide) (17 μl, 0 12 mmol) and 2,4,6-trιchlorobenzoyl chloride (19 μl, 0 12 mmol) over a period of 10 minutes After stirring at ambient temperature for 2 5 hours a solution of 4- dimethylaminopyπdine (29 mg, 0 14 mmol) and benzylic alcohol (25 μl, 0 24 mmol) in dry dichloromethane (0 19 ml) was added After stirring at ambient temperature for 15 hours, the reaction mixture was diluted with dichloromethane (5 ml) The resulting organic layer was successively washed with water (5 ml) with saturated sodium hydrogen carbonate solution (5 ml) with brine (5 ml) The resulting aqueous layer was extracted ith dichloromethane (10 ml), then the combined organic layers after drying over magnesium sulfate were evaporated to dryness The resulting crude product was purified by column chromatography (silica 15-40 μm (3g) dichloromethane then dichloromethane / methanol, 99 5 0 5 to 98 5 1 5) to provide the expected compound (40 mg, 55%) The product thus obtained showed the following characteristics 1 H NMR 400 MHz (CDCI3) ( ' ppm J Hz) 7 35 (5H, m, Ph), 6 58 (1 H, s, H-17), 6 47 (1 H s, H-14), 5 81 and 5 71 (2H, 2d, J AB = 1 4, OCH 2 0), 5 81 (1 H, d, J = 9 2, H-3), 5 08 and 4 99 (2H, 2d, J AB = 12 4, OCH 2 Ph) 5 0 (1 H, s, H-1 ), 3 70 (1 H, d, J 4 3 = 9 7, H-4), 3 63 (3H, s, OCH 3 ), 3 23 (1 H, m, H-1 1 β) 3 08 (1 H, m, H-8α), 2 93 (1 H, m, H-10α), 2 59 (2H m, H-8β + H- 10β), 2 37 (1 H, dd, J AB = 14 3, J = 7 0, H-1 1α), 2 16 and 1 80 (2H, 2d J AB = 14 3 CH 2 C0 2 ), 2 0 (1 H, m, H-6 A ), 1 90 (1 H, m H-6 B ), 1 75 (2H m, CH 2 -7), 1 6 - 0 8 (6H, m, 3 χ CH 2 ), 1 07 (3H, s, CH 3 ), 1 02 (3H, s CH 3 ) Example 8 Preparation of (-)-cephalotaxyl (2'R)-2-benzyloxycarbonylmethyi-6,6-dιmethyl-2- tetrahydropyrane carboxylate or 4'-benzyl-4'-demethyl-anhydro- homoharπnqtonine To a stirred mixture of 4'-demethy!-anhydro-homoharrιngtonιne (255 mg, 0 496 mmol) resulting from Example 2 in dry dichloromethane (1 8 ml) was added at 0°C triethylamine (dried over potassium hydroxide) (69 CI, 0 496 mmol) and 2,4,6-trιchlorobenzoyI chloride (78 μl 0 496 mmol) over a period of 10 minutes After stirring at ambient temperature for 2 5 hours a solution of 4- dimethylaminopyridine (121 mg 0 992 mmol) and benzylic alcohol (102 μl 0 992 mmol) in dry dichloromethane (0 8 ml) was added After stirring at ambient temperature for 15 hours, the reaction mixture was diluted with dichloromethane (0 8 ml) The resulting organic layer was successively washed with water (5 ml) with saturated sodium hydrogen carbonate solution (5 ml) with brine (5 ml) The resulting aqueous layer was extracted with dichloromethane (10 ml) then the combined organic layers after drying over magnesium sulfate were evaporated to dryness The resulting crude product was purified by column chromatography (silica 15-40 μm (8g), dichloromethane then dichloromethane / methanol, 99:1 to 98:2) to provide the expected compound (278 mg, 93%). The product thus obtained showed the following characteristics: IR (film ) (cm "1 ) : 1737 (C0 2 ), 1656 (C=C-0), 1504 (Ar), 1222 (C-O), 1 141 (C-O), 1081 (C-O), 1036 (C-O), 91 1. 1 H NMR 400 MHz (CDCI 3 ) (δ ppm, J Hz): 7.34 (5H, m, Ph), 6.60 (1 H, s, H-17), 6.52 (1 H, s, H-14), 5,91 (1 H, d, J = 9.8, H-3), 5.77 and 5.61 (2H, 2s, OCH 2 0), 5.05 (2H, s, OCH 2 Ph), 5.03 (1 H, s, H-1), 3.75 (1 H, d, J 4 . 3 = 9,7, H-4), 3.67 (3H, s, OCH 3 ), 3.1 1 (2H, m, H-1 1 β + H-8α), 2.93 (1 H, m, H-10α), 2.59 (2H, m, H-8β + H-10β), 2.36 (1 H, dd, J AB = 14.0, J = 6.6, H- 11α), 2.18 and 1.66 (2H, 2d, J AB = 14.5, CH 2 C0 2 ), 2.0 (1 H, m, H-6 Α ), 1 89 (1 H, m, H-6 B ), 1 ,75 (2H, m, CH 2 -7), 1 ,7 - 1 ,2 (6H, m, 3 χ CH 2 ), 1.06 (3H, s, CH 3 ), 1.04 (3H, s, CH 3 ), Example 9 Preparation of (-)-cephalotaxyl (2'R)-2-methylthiocarbonylmethyl-6,6-dimethyl-2- tetrahydropyrane carboxylate or 4'-methylthio-4'-demethoxy-anhydro- homohar nqtonine : To a stirred mixture of 4'-demethyl-anhydro-homoharringtonine (404 mg, 0,786 mmol) resulting from Example 2 in dry dichloromethane (2.75 ml) was added at 0 S C triethylamine (dried over potassium hydroxide) (105 μl, 0.786 mmol) and 2,4,6-trϊchlorobenzoyl chloride (123 μl, 0 786 mmol) over a period of 10 minutes. After stirring at ambient temperature for 2.5 hours a solution of 4- dimethylaminopyridine (192 mg, 1 57 mmol) in dry dichloromethane (0 8 ml) and methanethiol (218 μl, 1 57 mmol) Were added After stirring at ambient temperature for 15 hours, the reaction mixture Was diluted with dichloromethane (10 ml) The resulting organic layer was successively washed with water (14 ml), with saturated sodium hydrogen carbonate solution (14 ml), with brine (14 ml) The resulting aqueous layer was extracted with dichloromethane (20 ml), then the combined organic layers after drying over magnesium sulfate were evaporated to dryness The resulting crude product was purified by column chromatography (silica 15-40 μm (12g), dichloromethane then dichloromethane / methanol, 99 1 to 96 4) to provide the expected compound (228 mg, 53%) The product thus obtained showed the following characteristics IR (film ) (cm 1 ) 1741 (C0 2 ), 1690 (COS), 1656 (C=C-0), 1504 (Ar), 1222 (C-O), 1 142 (C-O), 1078 (C-O), 1035 (C-O), 913 1 H NMR 400 MHz (CDCI 3 ) (δ ppm, J Hz) 6 64 (1 H, s, H-14*), 6 58 (1 H, s, H-17*), 5 91 (1 H, d, J 3 4 = 9 7, H-3), 5 88 and 5 84 (2H, 2s, OCH 2 0), 5 04 (1 H, s, H-1 ), 3 79 (1 H, H-4), 3 70 (3H, s, OCH 3 ), 3 10 (2H, m, H-11 β + H-8σ), 2 95 (1 H, m, H-10α), 2 60 (2H, m, H-8β + H-10β), 2 35 (1 H, d, J AB = 14 5, CH A COS) and (1 H, m, H-1 1 α), 2 23 (3H, s, SCH 3 ), 2 03 (1 H, m, H-6 A ), 1 90 (1 H, m, H-6 B ), 1 75 (2H, m, CH 2 -7), 1 8 - 1 2 (7H, m, 3 χ CH 2 + CH B COS), 1 14 (3H, s, CH 3 ), 1 03 (3H, s, CH 3 ) Example 10 Preparation of (-)-cephalotaxyl (2'S)-2-ethylthiocarbonyimethyl-6,6-dimethyl-2- tetrahydropyrane carboxylate or 4'-ethylthιo-4'-demethoxy-anhydro-epι- homoharπnqtonme To a stirred mixture of 4'-demethyl-anhydro-epι-homoharrιngtonιne (70 mg, 0 136 mmol) resulting from Example 1 in dry dichloromethane (0 49 ml) was added at 0°C triethylamine (dried over potassium hydroxide) (19 μl, 0 136 mmol) and 2,4,6-trιchlorobenzoyI chloride (21 μl, 0 136 mmol) over a period of 10 minutes After stirring at ambient temperature for 2 5 hours a solution of 4- dimethylaminopyridine (33 mg, 0 272 mmol) and ethanethiol (20 μl, 0 272 mmol) in dry dichloromethane (0 25 ml) was added After stirring at ambient temperature for 15 hours, the reaction mixture was diluted with dichloromethane (5 ml). The resulting organic layer was successively washed with water (5 ml), with saturated sodium hydrogen carbonate solution (5 ml), with brine (5 ml) The resulting aqueous layer was extracted with dichloromethane (10 ml), then the combined organic layers after drying over magnesium sulfate were evaporated to dryness The resulting crude product was purified by column chromatography (silica 15-40 μm (2g), dichloromethane / methanol, 99 1 ) to provide the expected compound (40 mg, 53%) The product thus obtained showed the following characteristics 1 H NMR 400 MHz (CDCl3) (δ ppm, J Hz) 6 64 (1 H, s H-14 * ) 6 56 (1 H s H-17*), 5 87 and 5 83 (3H, 2d, J AB = 1 5 OCH 2 0 + H-3), 5 02 (1 H, s, H-1 ), 3 78 (1 H d, J . 3 = 9 7, H-4) 3 65 (3H, s, OCH 3 ), 3 24 (1 H, m, H-1 1 β), 3 09 (1 H, m, H-8σ) 2 95 (1 H, m, H-10u), 2 79 (2H, m, SCH 2 CH 3 ) 2 60 (2H, m, H-8β + H-10β) 2 41 (1 H, dd J AB = 14.2, J = 7 0, H-11 ) 2 28 and 1 83 (2H, 2d, J AB = 14 4, CH ? COS), 2 01 (1 H, m, H-6 A ) 1 91 (1 H, m H-6 B ), 1 75 (2H, m, CH 2 -7) 1 5 - 0 85 (6H m 3 χ CH 2 ), 1 20 (3H, t J = 7 4, SCH 2 CH 3 ) 1 14 (3H, s, CH 3 ), 1 01 (3H s CH 3 ). Example 11 Preparation of (-)-cephalotaxyl (2'R)-2-ethylthιocarbonylmethyl-6,6-dιmethyl-2- tetrahydropyrane carboxylate or 4'-ethylthιo-4'-demethoxy-anhydro- homoharπnqtonine To a stirred mixture of 4'-demethyl-anhydro-homoharrιngtonιne (250 mg, 0 486 mmol) resulting from Example 2 in dry dichloromethane (1 8 ml) was added at 0°C triethylamine (dried over potassium hydroxide) (68 μl, 0 486 mmol) and 2,4,6-trιchlorobenzoyl chloride (76 μl, 0 486 mmol) over a period of 10 minutes After stirring at ambient temperature for 2 5 hours a solution of 4- dimethylaminopyndine (1 19 mg, 0 973 mmol) and ethanethiol (72 μl, 0 973 mmol) in dry dichloromethane (0 8 ml) was added After stirring at ambient temperature for 15 hours, the reaction mixture was diluted with dichloromethane (5 ml) The resulting organic layer was successively washed with water (7 ml), with saturated sodium hydrogen carbonate solution (7 ml), with brine (7 ml) The resulting aqueous layer was extracted with dichloromethane (10 ml), then the combined organic layers after drying over magnesium sulfate were evaporated to dryness The resulting crude product was purified by column chromatography (silica 15-40 μm (7g), dichloromethane then dichloromethane / methanol, 99 1 to 98 2) to provide the expected compound (251 mg, 93%) The product thus obtained showed the following characteristics IR (film cm 1740 (C0 2 ), 1688 (COS) 1657 (C=C-0), 1504 (Ar), 1223 (C-O), 1142 (C-O), 1078 (C-O), 1037 (C-O) 910 1 H NMR 400 MHz (CDCI3) (ό ppm, J Hz) 664 (1H s H-14*), 659 (1H s H-17*), 5.91 (1H H-3) 590 and 5.85 (2H 2s OCH 2 0) 503 (1H, s, H-1), 380 (1H, H-4) 3.71 (3H, s, OCH 3 ) 314 (2H , H- 1 1 β + H-8α), 2 88 (1 H, m, H-10α). 2 81 (2H, m, SCH 2 CH3), 2 61 (2H, m, H-8« I + H-10β), 2 38 (1 H, m, H-11 D), 2 35 (1 H, d, JAB = 14 8, Cfc COS), 2 02 (1 H, m, H- 6 A ), 1 91 (1 H, m, H-6 B ), 1 77 (2H, m, CH 2 -7), 1 65 - 1 1 (7H, m, 3 χ CH 2 + CH R CQS), 1 20 (3H, t, J = 7 4, SCH 2 CH 3 ), 1 14 (3H, s, CH3), 1 02 (3H, s, CH3) Example 12 Preparation of (-)-cephalotaxyl (2'S)-2-ιsopropylthιocarbonylmethyl-6,6-dιmethyl- 2-tetrahydropyrane carboxylate or 4'-ιsopropylthιo-4'-demethoxy-anhydro-epι- homoharrin tonine To a stirred mixture of 4'-demethyl-anhydro-epι-homoharrιngtonιne (49 mg 0 095 mmol) resulting from Example 1 in dry dichloromethane (0 34 ml) was added at 0°C triethylamine (dried over potassium hydroxide) (13 μl, 0 095 mmol) and 2,4,6-trιchlorobenzoyl chloride (15 μl, 0 095 mmol) over a period of 10 minutes After stirring at ambient temperature for 2 5 hours a solution of 4- dimethylaminopyπdine (23 mg, 0 19 mmol) and isopropanethiol (18 μl, 0 19 mmol) in dry dichloromethane (0 2 ml) was added After stirring at ambient temperature for 15 hours, the reaction mixture was diluted with dichloromethane (5 ml) The resulting organic layer was successively washed with water (5 ml), with saturated sodium hydrogen carbonate solution (5 ml), with brine (5 ml) The resulting aqueous layer was extracted with dichloromethane (10 ml), then the combined organic layers after drying over magnesium sulfate were evaporated to dryness The resulting crude product was purified by column chromatography (silica 15-40 Mm (1 g) dichloromethane / methanol, 99.1 ) to provide the expected compound (40 mg, 74%). The product thus obtained showed the following characteristics 1 H NMR 400 MHz (CDCI 3 ) (δ ppm, J Hz) 6 64 (1 H, s, H-14*), 6 57 (1 H, s, H-17*), 5 87 (3H, 2d, J AB = 1 4 OCH 2 0 + H-3) 5 02 (1 H s, H-1 ), 3 78 (1 H, d J 4 3 = 9 7, H-4), 3 65 (3H, s 0CH 3 ) 3 55 (1 H, m J = 6 9, CH(CH 3 ) 2 ), 3 23 (1 H, m H-11 β), 3 09 (1 H m, H-8α) 2 94 (1 H, m H-10σ) 2 60 (2H, m, H-8β + H-10β), 2 42 (1 H, dd, J AB = 13 9, J = 6 8, H-11 α), 2 25 and 1 79 (2H, 2d, J AB = 14 3, CH 2 COS), 2 04 (1 H, m, H-6 A ), 1 90 (1 H, m, H-6 B ), 1 75 (2H, m, CH 2 -7), 1 45 - 0 85 (6H, m, 3 χ CH 2 ), 1 25 (6H, d, J = 6 9, CH(CH 3 ) 2 ), 1 14 (3H, s, CH 3 ), 1 01 (3H, s, CH 3 ) Example 13 Preparation of (-)-cephalotaxyl (2'R)-2-ιsopropylthιocarbonylmethyl-6,6-dιmethyl- 2-tetrahydropyrane carboxylate or 4'-ιsopropylthιo-4'-demethoxy-anhydro- homoharnnqtonine To a stirred mixture of 4'-demethyl-anhydro-homoharrιngtonιne (248 mg 0 483 mmol) resulting from Example 2 in dry dichloromethane (1 8 ml) was added at 0°C triethylamine (dried over potassium hydroxide) (67 μl, 0 483 mmol) and 2,4,6-trιchlorobenzoyl chloride (76 μl, 0 483 mmol) over a period of 10 minutes After stirring at ambient temperature for 2 5 hours a solution of 4- dimethylaminopyπdine (120 mg 0 965 mmol) and isopropanethiol (90 μl 0 965 mmol) in dry dichloromethane (0 8 ml) was added After stirring at ambient temperature for 15 hours the reaction mixture was diluted with dichloromethane (5 ml) The resulting organic layer was successively washed with water (7 ml) with saturated sodium hydrogen carbonate solution (7 ml), with brine (7 ml) The resulting aqueous layer was extracted with dichloromethane (10 ml) then the combined organic layers after drying over magnesium sulfate were evaporated to dryness The resulting crude product was purified by column chromatography (silica 15-40 Dm (8g), dichloromethane then dichloromethane / methanol, 99 1 to 98 2) to provide the expected compound (267 mg, 97%) The product thus obtained showed the following characteristics IR (film ) (cm 1 ) 1740 (C0 2 ), 1687 (COS), 1656 (C=C-O), 1504 (Ar), 1223 (C-O), 1 142 (C-O), 1078 (C-O), 1036 (C-O), 912 1 H NMR 400 MHz (CDCI 3 ) (δ ppm, J Hz) 664 (1H, s, H-14*), 658 (1H, s, H-17 * ), 591 (1H, d, J 34 = 97, H-3), 589 and 585 (2H, 2s, OCH 2 0), 504 (1H, s, H-1), 379 (1H, d, H-4), 371 (3H, s, OCH 3 ), 356 (1H, , J = 69, CH(CH 3 ) 2 ), 318 (2H, m, H-11 β + H-8α), 299 (1H, m, H-10α), 261 (2H, m, H-8β + H-10β), 239 (1H, m, H-11α), 231 (1H, d, J AB = 143, CH A COS), 204 (1H, m, H-6 A ), 192 (1H, m, H-6 B ), 178 (2H, m, CH2-7), 17 - 12 (7H, m, 3 χ CH2 + CH R COS), 125 and 124 (6H, 2d, J = 68, CH(CH 3 ) 2 ), 113 (3H, s, CH3), 10 (3H, s, CH3) Example 14 Preparation of (-)-cephalotaxyl (2'S)-2-tert-butylthιocarbonylmethyl-6,6-d[methyl-2- tetrahydropyrane carboxylate or 4 > -tert-butylthιo-4'-demethoxy-anhydro-epι- homoharrin tonine To a stirred mixture of 4'-demethyl-anhydro-epι-homoharrιngtonιne (70 mg, 0 136 mmol) resulting from Example 1 in dry dichloromethane (0 49 ml) was added at 0°C triethylamine (dried over potassium hydroxide) (19 μl 0 136 mmol) and 2 4,6-trιchlorobenzoyl chloride (21 μl, 0.136 mmol) over a period of 10 minutes. After stirring at ambient temperature for 2 5 hours a solution of 4- dimethylaminopyridine (33 mg 0 272 mmol) and terf-butanethiol (31 μl, 0 272 mmol) in dry dichloromethane (0 3 ml) was added After stirring at ambient temperature for 15 hours, the reaction mixture was diluted with dichloromethane (5 ml) The resulting organic layer was successively washed with water (5 ml) with saturated sodium hydrogen carbonate solution (5 ml), with brine (5 ml) The resulting aqueous layer was extracted with dichloromethane (10 ml), then the combined organic layers after drying over magnesium sulfate were evaporated to dryness The resulting crude product was purified by column chromatography (silica 15-40 μm (1 5g), dichloromethane / methanol, 99 1 ) to provide the expected compound (46 mg, 58%) The product thus obtained showed the following characteristics 1 H NMR 400 MHz (CDCI3) (δ ppm, J Hz) 6 65 (1 H, s, H-14*), 6 56 (1 H, s, H-17*), 5 87 and 5 84 (2H, .2d J AB = 1 5, OCH 2 O), 5 84 (1 H, d, J 3 4 = 10 0, H-3), 5 02 (1 H, s, H-1 ), 3 78 (1 H, d, J 4 3 = 9 6, H- 4), 3 64 (3H, s, OCH 3 ), 3 24 (1 H, m, H-11 β), 3 09 (1 H, m, H-8α), 2 96 (1 H, m, H- 10α), 2 60 (2H, m, H-8β + H-10β), 2 42 (1 H, dd, J AB = 14 3, J = 7 0, H-1 1 α), 2 20 and 1 71 (2H, 2d, J AB = 14 1 , CH 2 COS), 2 01 (1 H, m, H-6 A ), 1 88 (1 H, m, H-6 B ), 1 75 (2H, m, CH 2 -7), 1 6 - 0 85 (6H, m, 3 χ CH 2 ) 1 41 (9H, s, C(CH3)3 ), 1 13 (3H, s, CH 3 ), 1 01 (3H, s, CH 3 ) Example 15 Preparation of (-)-cephalotaxyl (2'R)-2-tert-butylthιocarbonylmethyl-6,6-dιmethvJ~ 2-tetrahydropyrane carboxylate or 4'-tert-butylthto-4 -demethoxy-anhydro- homoharnnqtonine To a stirred mixture of 4'-demethyl-anhydro-homoharrιngtonιne (234 mg 0 455 mmol) resulting from Example 2 in dry dichloromethane (1 8 ml) was added at 0°C triethylamine (dried over potassium hydroxide) (63 μl, 0 455 mmol) and 2,4,6-trιchlorobenzoyl chloride (72 μl, 0 455 mmol) over a period of 10 minutes After stirring at ambient temperature for 2 5 hours a solution of 4- dimethylaminopyπdine (1 11 mg, 0 911 mmol) and terf-butanethiol (102 μl, 0 91 1 mmol) in dry dichloromethane (0 8 ml) was added After stirring at ambient temperature for 15 hours, the reaction mixture was diluted with dichloromethane (5 ml) The resulting organic layer was successively washed with water (7 ml), with saturated sodium hydrogen carbonate solution (7 ml), with brine (7 ml) The resulting aqueous layer was extracted with dichloromethane (10 ml), then the combined organic layers after drying over magnesium sulfate were evaporated to dryness The resulting crude product was purified by column chromatography (silica 15-40 μm (6g), dichloromethane then dichloromethane / methanol, 99 1 to 98 2) to provide the expected compound (212 mg, 81%) The product thus obtained showed the following characteristics IR (film ) (cm "1 ) 1738 (C0 2 ), 1681 (COS), 1659 (C=C-0), 1504 (Ar), 1222 (C-O) 1141 (C-O), 1077 (C-O), 1037 (C-O), 911 1 H NMR 400 MHz (CDCI 3 ) (δ ppm, J Hz) 6 65 (1 H, s, H-14*), 6 59 (1 H, s, H-17*), 5 89 (3H, m, OCH 2 0 + H-3), 5 03 (1 H, s, H-1 ), 3 76 (1 H, H-4), 3 72 (3H, s, OCH 3 ), 3 13 (2H, m, H-1 1 β + H-8α), 3 0 (1 H, m, H-10α), 2 63 (2H, m, H-8β + H-10β), 2 40 (1 H, m, H-1 l ot), 2 23 (1 H, d, J AB = 12 2, CH A COS), 2 01 (1 H, m, H-6A), 1 93 (1 H, m, H-6B), 1 78 (2H, m, CH2-7), 1 7 - 1 2 (6H, m, 3 χ CH2 + CH B COS), 1 41 (9H, s, C(CH 3 ) 3 ), 1 12 (3H, s, CH 3 ), 0 99 (3H, s, CH 3 ) Example 16 Preparation of (-)-cephalotaxyl (2'S)-2-(methylamιno)carbonylmethyl-6,6-dιmethyl- 2-tetrahydropyrane carboxylate or 4 -methylamιno-4'-demethoxy-anhydro-epι- homoharnnqtonine . To a stirred mixture of 4'-demethyl-anhydro-epι-homoharrιngtonιne (52 mg, 0 10 mmol) resulting from Example 1 in dry dichloromethane (0 34 ml) was added at 0°C triethylamine (dried over potassium hydroxide) (14 μl, 0 10 mmol) and 2,4,6-trιchlorobenzoyl chloride (15 5 μl, 0 10 mmol) over a period of 10 minutes After stirring at ambient temperature for 2 5 hours a solution of 4- dimethylaminopyπdine (49 mg 0 40 mmol) in dry dichloromethane (0 3 ml) and methylamine hydrochloride (13 5 mg, 0 20 mmol) were added After stirring at ambient temperature for 15 hours the reaction mixture was diluted with dichloromethane (5 ml) The resulting organic layer was successively washed with water (5 ml), with saturated sodium hydrogen carbonate solution (5 ml) The resulting aqueous layer was extracted with dichloromethane (10 ml), then the combined organic layers after drying over magnesium sulfate were evaporated to dryness The resulting crude product was purified by column chromatography (silica 15-40 μm (2g), dichloromethane then dichloromethane / methanol, 98 2) to provide the expected compound (47 mg 89 %) The product thus obtained showed the following characteristics 1 H NMR 400 MHz (CDCI 3 ) (δ ppm, J Hz) 6 61 (1 H, s H-14*), 6 59 (1 H, s, H-17*), 6 48 (1 H m , NH) , 5 85 (3H, m, OCH 2 0 + H-3) 5 03 (1 H, s, H-1 ) 3 79 (1 H d, J 4 3 = 9 7, H-4), 3 67 (3H, s, OCH 3 ) 3 17 (1 H, m, H-1 1 β), 3 09 (1 H, m, H-8σ) 2 93 (1 H m H-10α), 2 74 (3H, d J = 4.9 NHCH 3 ) , 2 59 (2H, m, H-8β + H-10β) 2 37 (1 H dd, J AB = 14 2 J = 7 0, H-1 1 α) 2 1 1 and 1 84 (2H, 2d, J AB = 14 5 CH 2 CON), 2 02 (1 H m H-6 A ) 1 89 (2H m H- 6 B + CH) 1 75 (2H, m, CH 2 -7), 1 4 - 1 1 (5H m CH + 2 χ CH 2 ), 1 18 (3H, s CH 3 ) 0 96 (3H s, CH 3 ) Example 17 Preparation of (-)-cephalotaxyl (2'S)-2-(dιmethylamιno)carbonylmethyl-6,6- dιmethyl-2-tetrahydropyrane carboxylate or 4'-dιmethylamιno-4'-demethoxy- anhydro-epi-homoharπnqtonine To a stirred mixture of 4'-demethyl-anhydro-epι-homoharrιngtonιne (60 mg, 0 1 17 mmol) resulting from Example 1 in dry dichloromethane (0 4 ml) was added at 0°C triethylamine (dried over potassium hydroxide) (16 2 μl 0 11 1 mmol) and 2,4,6-trιchlorobenzoyl chloride (18 μl, 0 117 mmol) over a period of 10 minutes After stirring at ambient temperature for 2 5 hours a solution of 4- dimethylaminopyndine (28 6 mg, 0 234 mmol) in dry dichloromethane (0 16 ml) and dimethylamme (in excess) were added After stirring at ambient temperature for 15 hours, the reaction mixture was diluted with dichloromethane (5 ml) The resulting organic layer was successively washed with water (5 ml), with saturated sodium hydrogen carbonate solution (5 ml), with brine (5 ml) The resulting aqueous layer was extracted with dichloromethane (10 ml), then the combined organic layers after drying over magnesium sulfate were evaporated to dryness The resulting crude product was purified by column chromatography (silica 15-40 μm (1 5g) dichloromethane then dichloromethane / methanol, 99 1 to 98 2) to provide the expected compound (1 1 mg, 17 4 %) The product thus obtained showed the following characteristics 1 H NMR 400 MHz (CDCI 3 ) (δ ppm J Hz) 6 59 (2H s, H-17 + H-14), 5 88 (1 H d, J3-4 = 9 7, H-3) 5 84 (2H s OCH 2 0) 5 01 (1 H s H-1 ) 3 80 (1 H d, J 4 . 3 = 9 9, H-4), 3 66 (3H s OCH 3 ), 3 23 (1 H m, H- 1 1 β), 3 09 (1 H m, H-8α) 2 95 (1 H m H-10ι/) and (3H s, NCH 3 ) 2 88 (3H s NCH 3 ) 2 60 (2H m H-8 ' + H-1 Op) 2 37 (1 H m, H-11 ) 2 35 and 1 73 (2H 2d J AB = 13 5, CH 2 CON), 2 01 (2H, m, CH 2 -6), 1 95 - 1 10 (8H m, CH2-7 + 3 χ CH 2 ), 1 08 (3H, s, CH 3 ), 0 96 (3H, s, CH 3 ) Example 18 Preparation of (-)-cephalotaxyl (2'S)-2-(dιethylamιno)carbonylmethyl-6,6-dιmethyl- 2-tetrahydropyrane carboxylate or 4'-dιethylamιno-4'-demethoxy-anhydro-epι- homohamn tonine To a stirred mixture of 4'-demethyl-anhydro-epι-homoharrιngtonιne (57 mg, 0 11 mmol) resulting from Example 1 in dry dichloromethane (0 34 ml) was added at 0°C triethylamine (dried over potassium hydroxide) (15 3 μl, 0 11 mmol) and 2,4,6-trιchlorobenzoyl chloride (17 1 μl, 0 1 1 mmol) over a period of 10 minutes After stirring at ambient temperature for 2 5 hours a solution of 4- dimethylaminopyπdine (27 4 mg, 0 22 mmol) and diethylamine (23 μl, 0 22 mmol) in dry dichloromethane (0 16 ml) was added After stirring at ambient temperature for 15 hours, the reaction mixture was diluted with dichloromethane (5 ml) The resulting organic layer was successively washed with water (5 ml), with saturated sodium hydrogen carbonate solution (5 ml), with brine (5 ml) The resulting aqueous layer was extracted with dichloromethane (10 ml), then the combined organic layers after drying over magnesium sulfate were evaporated to dryness The resulting crude product was purified by column chromatography (silica 15-40 μm (1 5g), dichmoromethane then dichloromethane / methanol, 99 1 to 98 2) to provide the expected compound (50 mg, 80%) The product thus obtained showed the following characteristics 1 H NMR 400 MHz (CDCI 3 ) (o ppm J Hz)- 6 60 (1 H, s, H-14*), 6 58 (1 H, s, H-17*), 5 84 (3H, m, OCH 2 0 + H-3), 5 02 (1 H, s, H-1 ), 3 81 (1 H, d, J 4 3 = 9 6, H-4), 3 69 (2H, m, NCH 2 CH 3 ), 3 66 (3H, s, OCH 3 ), 3 21 (1 H, m, H-1 1 β), 3 08 (1 H, m, H-8α), 2 95 (3H, m, H-10α + NCH 2 CH 3 ), 2 60 (2H, m, H-8β + H-1 Oβ), 2 41 and 1 71 (2H, 2d, J AB = 13 3, C_H 2 COn), 2 37 (1 H, dd, J AB = 14 2, J = 7 0, H-1 1α), 2 01 (1 H, m, H-6 A ), 2 0 - 1 0 (6H, m 3 χ CH 2 ), 1 89 (1 H, m, H-6 B ), 1 75 (2H, m, CH 2 -7), 1 10 (9H m, N(CH 2 CH 3 ) 2 + CH 3 ), 0 92 (3H, s CH 3 ) Example 19 Preparation of (-)-cephalotaxyl (2'R)-2-(dιethylamιno)carbonylmethyl-6,6-dιmethyl- 2-tetrahydropyrane carboxylate or 4'-dιethylamιno-4'-demethoxy-anhydro- homoharπnqtonine To a stirred mixture of 4'-demethyl-anhydro-homoharπngtonιne (250 mg, 0 487 mmol) resulting from Example 2 in dry dichloromethane (1 8 ml) was added at 0°C triethylamine (dried over potassium hydroxide) (65 μl, 0 487 mmol) and 2,4,6-trιchlorobenzoyl chloride (76 μl, 0 487 mmol) over a period of 10 minutes After stirring at ambient temperature for 2 5 hours a solution of 4- dimethylaminopyπdine (1 19 mg 0.974 mmol) and diethylamine (105 μl 0 974 mmol) in dry dichloromethane (0 8 ml) was added, After stirring at ambient temperature for 15 hours, the reaction mixture was diluted with dichloromethane (5 ml) The resulting organic layer was successively washed with water (5 ml), with saturated sodium hydrogen carbonate solution (5 ml), with brine (5 ml) The resulting aqueous layer was extracted ith dichloromethane (10 ml), then the combined organic layers after drying over magnesium sulfate were evaporated to dryness The resulting crude product was purified by column chromatography (silica 15-40 Dm (8g), dichloromethane then dichloromethane / methanol, 99 1 to 97 3) to provide the expected compound (226 mg, 82%) The product thus obtained showed the following characteristics 1 H NMR 400 MHz (CDCI 3 ) (δ ppm, J Hz) 6 63 (1 H, s, H-14*), 6 59 (1 H, s, H-17*), 5 86 (1 H, d, J 3 4 = 9 6, H-3), 5 82 and 5 78 (2H, 2s, OCH 2 0), 5 04 (1 H, s, H-1 ), 3 81 and 3 72 (2H, 2m, NCH 2 CH 3 ), 3 80 (1 H, d, H-4), 3 70 (3H, s, OCH 3 ), 3 12 (2H m, H-1 1 β + H-8α), 2 90 (3H m, H- 10α + NCH 2 CH 3 ), 2 59 (2H, m, H-8β + H-10β), 2 38 (1 H dd, J AB = 14 2 J = 6 7, H-11α), 2 24 (1 H, d, J AB = 13 1 , CHACOIM), 2 02 (1 H, m, H-6 A ), 1 95 - 1 15 (10H m, H-6 B + CH 2 -7 + CH 8 CON + 3 χ CH 2 ), 1 06 and 1 03 (6H, 2t, J = 7 1 N(CH 2 CH 3 ) 2 ), 1 04 (3H, s, CH 3 ) , 0 92 (3H, s, CH 3 ) Example 20 Preparation of (-)-cephalotaxyl (2'S)-2-(but-2-enyl)oxycarbonylmethyl-6,6- dιmethyl-2-tetrahydropyrane carboxylate or 4'-(but-2-enyl)-4'-demethyl-anhydro- epi-homoharrinqtonine 1 °) Method A To a stirred mixture of 4'-dernethyl~anhydro-epι-hornoharrιngtonιne (60 mg 0 12 mmol) resulting from Example 1 in dry dichloromethane (0 35 ml) was added at 0°C triethylamine (dried over potassium hydroxide) (17 μl 0.12 mmol) and 2 4 6-trιchlorobenzoyl chloride (19 μl 0 12 mmol) over a period of 10 minutes After stirring at ambient temperature for 2 5 hours a solution of 4- dimethylaminopyπdine (29 mg, 0 14 mmol) and crotyl alcohol (17 μl, 0 24 mmol) in dry dichloromethane (0 19 ml) was added After stirring at ambient temperature for 72 hours, the reaction mixture was diluted with dichloromethane (5 ml) The resulting organic layer was successively washed with water (5 ml) with saturated sodium hydrogen carbonate solution (5 ml), with brine (5 ml) The resulting aqueous layer was extracted ith dichloromethane (10 ml), then the combined organic layers after drying over magnesium sulfate were evaporated to dryness The resulting crude product was purified by column chromatography (silica 15-40 μm (1g), dichloromethane then dichloromethane / methanol, 99 1 to 97 3) to provide the expected compound (36 mg, 55%) The product thus obtained showed the following characteristics 1 H NMR 400 MHz (CDCI3) (δ ppm, J Hz) 6 61 (1 H, s, H-17*), 6 57 (1 H, s, H-14*), 5 85 and 5 81 (2H, 2d J AB = 1 4, OCH 2 0), 5 83 (1 H, d, J 3 2 = 9 6, H-3) , 5 75 (1 H, dq, J c b = 15 2, J c d = 6 5, H-c) , 5 55 (1 H, m J b c = 15 3, H-b) , 5 02 (1 H, s, H-1 ), 4 46 and 4 38 (2H, 2dd, J AB = 12 3 J a b = 6 5, CH 2 -a) , 3 77 (1 H, d, J 4 3 = 9 7, H-4), 3 65 (3H, s OCH 3 ), 3 23 (1 H, m, H-11 β), 3 09 (1 H, m, H-8α), 2 95 (1 H, m, H-10α), 2 61 (2H, m, H-8β + H- 10β), 2 40 (1 H, dd, J AB = 14 2, J = 6 6, H-11α), 2 13 and 1 78 (2H, 2d J AB = 14 3, CH 2 C0 2 ), 2 01 (1 H m, H-6 A ), 1 90 (1 H, m, H-6 B ), 1 76 (2H, m, CH 2 -7), 1 71 (3H, dd, J d c = 6 5, J d b = 1 1 , CH 3 d ) 1 55 - 1 2 (6H, m, 3 χ CH 2 ), 1 1 1 (3H s, CH 3 ), 1 01 (3H, s, CH 3 ) 2°) Method B Sodium hydride 60% (10 mg 0 228 mmol) was added to a solution of anhydro-epi-homoharπngtonine (100 mg 0 18 mmol) resulting from Example 1 in crotyl alcohol (1 ml) and the resulting mixture was stirred at ambient temperature for 72 hours After neutralization by addition of hydrochloric acid 1 N, dilution with water (5 ml) and saturation with sodium chloride, the resulting aqueous layer was extracted with dichloromethane (3 x 5 ml) The combined organic layers were dried over magnesium sulfate and evaporated to dryness The resulting crude product was purified by column chromatography (silica 15-40 μm (2g), dichloromethane then dichloromethane / methanol 99 1 ) to provide the expected product (66 mg, 62%) The product thus obtained showed identical characteristics to this obtained with method A Example 21 Preparation of (-)-cephalotaxyl (2'R)-2-(but-2-enyl)oxycarbonylmethyl-6,6- dιmethyl-2-tetrahydropyrane carboxylate or 4'-(but-2-enyl)-4'-demethyl-anhydto- homoharπnqtonine Sodium hydride 60 % (21 9 mg, 0 9 mmol) was added to a solution of anhydro-homoharringtonine (400 mg, 0 767 mmol) in 3-methyl-2-bUtenol (4 ml) and the resulting mixture was stirred at ambient temperature for 36 hours under argon After dilution with water (50 ml) the aqueous layer was extracted with dichloromethane (3 x 20 ml) The combined organic layers were diluted with dichloromethane (150 ml), washed with water (50 ml), dried over magnesium sulfate and evaporated to dryness (350 mg crude, 81 %) The crude product thus obtained was purified by column chromatography (silica 15-40 μm (5g), dichloromethane then dichloromethane / methanol, 95 5) to provide the expected product (105 mg, 24 5%) The product thus obtained showed the following characteristics 1 H NMR 400 MHz (CDCI 3 ) (δ ppm, J Hz) 6 61 (1 H, s H-17*), 6 57 (1 H, s H-14*), 5 91 (1 H, d J 3 . 2 = 9 4, H-3) 5.86 and 5 78 (2H, 2d, JAB = 1 4, OCH 2 0), 5 72 (1 H, m, H-c) , 5 55 (1 H, m H-b) , 5 03 (1 H, s, H-1), 4 43 (2H, m, CH 2 -a) , 3 78 (1 H, d J 4 . 3 = 9 7 H-4) 3 69 (3H, s OCH 3 ), 3 1 1 (2H, m, H-1 1 β + H-8α), 2 94 (1 H m, H-10α), 2 59 (2H, m, H-8β + H- 10β) 2 36 (1 H, dd, J AB = 14 1 , J = 6 9 H-11α), 2 13 and 1 60 (2H, 2d, J AB = 14 43, CH 2 C0 2 ), 2 0 (1 H, m, H-6 A ) 1 89 (1 H m, H-6 B ) 1 75 (2H, m CH 2 -7), 1 71 (3H dd, J d . c = 5 5, J d . b = 1 1 CH 3 -d) ,1 7 - 1 2 (6H, m, 3 χ CH 2 ) 1 10 (3H, s CH 3 ) 1 04 (3H, s, CH 3 ) Example 22 Preparation of 4'-demethyl-epι-homoharrιnqtonιne from epi-homoharrinqtonine To a stirred solution of epi-homoharπngtonine (266 mg, 0 488 mmol) in methanol (6 7 ml) was added lithium hydroxide (119 mg, 0 488 mmol) and water (2 2 ml) After stirring 5 hours at ambient temperature 1 N hydrochloric acid was added to pH 7 and ethanol was evaporated under reduced pressure After addition of dichloromethane (10 ml), the residual aqueous layer is exhausted by tnturation with magnesium sulfate The solid removed by filtration was washed with dichloromethane (4 > 2 ml) and the combined organic layers were dried over magnesium sulfate and evaporated to dryness to provide the expected compound (128 mg crude, 49%) The crude product thus obtained showed the following characteristics 1 H NMR 400 MHz (DMSO-d s ) (δ ppm, J Hz) 6 64 (1 H, s, H-17*), 6 57 (1 H s, H-14*), 5 90 (2H, s, OCH 2 0), 5 75 (1 H, d, J 3 4 = 9 5, H-3), 5 1 1 (1 H, s, H-1 ), 3 95 (1 H, s, 2'-OH), 3 78 (1 H, d, J 4 3 = 9 7, H-4), 3 58 (3H, s, OCH 3 ), 3 06 (1 H m, H-1 1 β), 2 81 (1 H, m, H-8α) 2 68 (1 H, m, H-10α) 2 52 (2H, m H-8β + H-10β) 2 33 (1 H, dd, J AB = 13 4 J = 6 3 H-1 1 σ) 2 0 (2H m, CH 2 C0 2 ) , 1 9 - 0 6 (1 OH m CH 2 -6 + CH 2 -7 + 3 χ CH 2 ), 0 99 (3H s CH 3 ), 0 97 (3H, s, CH 3 ) Example 23 Preparation of 4'-demethyl-homohamnqlonme from homohaninqtonme To a stirred solution of homoharπngtonine (60 mg, 0 1 1 mmol) in methanol (1 5 ml) was added lithium hydroxide (27 mg, 1 1 mmol) and water (0 5 ml) After stirring 15 hours at ambient temperature 1 N hydrochloric acid was added to pH 7-8 and ethanol was evaporated under reduced pressure After addition of dichloromethane (5 ml), the residual aqueous layer is exhausted by tnturation with magnesium sulfate The solid removed by filtration was washed with dichloromethane (4 x 2 ml) and the combined organic layers were dried over magnesium sulfate and evaporated to dryness to provide the expected compound (28 mg crude, 48%) The crude product thus obtained showed the following characteristics IR (film ) (cm -1 ) • 3600-2800 (C0 2 H, OH), 1738 (C0 2 ), 1657 (C=C-0), 1505 (Ar), 1223 (C-O), 1166 (C-O), 1080 (C-O), 1041 (C-O), 912 1 H NMR 400 MHz (DMSO-d 6 ) (δ ppm, J Hz) 663 (1H, s, H-17*), 654 (1H, s, H-14*), 589 + 586 (2H, 2s, OCH 2 0), 570 (1H, d, J 34 = 96, H-3), 513 (1H, s, H-1), 402 (1H, s, 2'-OH), 377 (1H d J 4 . 3 = 96, H- 4), 359(3H, s, OCH 3 ), 304(1H, m, H-11β), 281 (1H, td J = 87 and 36), H-8α), 269 (1H, m, H-10α), 252 (2H m, H-8β + H-10β), 233 (1H, dd, J AB = 140, J = 70, H-11α), 186 (1H, m, H-6 A ), 181 (1H, m H-6 B ), 168 + 157 (4H, 2m, CH 2 -7 + CH 2 C0 2 ), 116 (6H, m, 3 χ CH 2 ), 102 (3H, s, CH 3 ), 101 (3H, s, CH 3 ) Example 24 Preparation of (2 S)-4'-ethyl-4'-demethyl-epιøomohamnqtonιne 1°) Method A To a stirred solution of 4'-ethyl-4'-demethyl-anhydro-epι-homoharrιngtonιne (59 mg, 0 109 mmol) resulting from Example 3 in dry dichloromethane (0 3 ml) under nitrogen was added at -10°C a commercial solution of hydrobromic acid in acetic acid (0 195 ml, 0 98 mmol, HBr 30% w/w) After stirring at -10°C for 3 hours was added water (2 8 ml) and the temperature was raised to 20°C After stirring at 20°C for 3 hours, was added a sodium carbonate solution (0 76 M, 6 ml) up to pH 8 The resulting aqueous layer, after saturation with sodium chloride, was extracted with dichloromethane (3 x 10 ml) and the combined organic layers were dried over magnesium sulfate and evaporated to dryness to provide the expected compound (46 mg crude, 76%>) The crude product thus obtained showed the following characteristics 1 H NMR 400 MHz (CDCI 3 ) (δ ppm, J Hz) 6 64 (1 H s, H-17 * ), 6 59 (1 H, s, H-14 * ), 5 95 and 5 85 (2H, 2d, J AB = 1 3, OCH 2 0), 5 94 (1 H, d, J 3 4 = 9 3, H-3), 5 03 (1 H, s, H-1 ), 4 1 1 (2H, m, OCH 2 CH 3 ), 3 78 (1 H, d, J 4 . 3 = 9 8, H-4), 3 65 (3H, s, OCH 3 ), 3 52 (1 H, s, 2 -OH), 3 09 (2H, m, H-1 1 β + H-8α), 2 93 (1 H, m, H-10α), 2 59 and 2 51 (2H, 2d J AB = 16 6, CH 2 C0 2 ), 2 57 (2H, m, H-8β + H-10β), 2 38 (1 H, dd, J AB = 14 2, J = 6 8, H-1 1 ), 2 02 (1 H, m, H-6 A ), 1 89 (1 H, m, H-6 B ), 1 71 (2H, m, CH 2 -7), 1 5 - 0 6 (6H, m 3 χ CH 2 ), 1 24 (3H, t J = 7 2, OCH 2 CH 3 ), 1 16 (3H, s, CH 3 ) 1 15 (3H, s CH 3 ) 2°) Method B To a stirred mixture of 4'-demethy!-epι-homoharrιngtonιne (40 mg, 0 075 mmol) resulting from Example 22 in dry dichloromethane (0 26 ml) was added at 0°C triethylamine (dried over potassium hydroxide) (10 μl, 0 075 mmol) and 2,4 6-trιchlorobenzoyl chloride (12 μl 0 075 mmol) over a period of 10 minutes After stirring at ambient temperature for 2 5 hours a solution of 4- dimethylaminopyridine (18 4 mg, 0 15 mmol) and ethanol (8 μl, 0,138 mmol) in dry dichloromethane (0 16 ml) was added After stirring at ambient temperature for 15 hours, the reaction mixture was diluted with dichloromethane (10 ml) The resulting organic layer was successively washed with water (5 ml), with saturated sodium hydrogen carbonate solution (5 ml) with brine (5 ml) The resulting aqueous layer was extracted with dichloromethane (10 ml), then the combined organic layers after drying over magnesium sulfate were evaporated to dryness The resulting crude product was purified by column chromatography (silica 15-40 □ m (1g), dichloromethane then dichloromethane / methanol, 99 1 to 98 2) to provide the expected compound (1 1 mg, 26 %) The product thus obtained showed identical characteristics to this obtained with method A Example 25 Preparation of (2 R)-4'-ethyl-4'-demethyl-homoharrιnqtonιne 1°) Method A To a stirred solution of 4'-ethyl-4 -demethyl-anhydro-homoharrιngtonιne (220 mg 0 406 mmol) resulting from Example 4 in dry dichloromethane (1 1 ml) under nitrogen was added at -10°C a commercial solution of hydrobromic acid in acetic acid (0 728 ml 3 6 mmol, HBr 30% w/w) After stirring at -10°C for 3 hours, was added water (10 ml) and the temperature was raised to 20°C After stirring at 20°C for 3 hours was added a sodium carbonate solution (0 76 M 31 5 ml) up to pH 8-9 The resulting aqueous layer, after saturation with sodium chloride was extracted with dichloromethane (3 x 20 ml) and the combined organic layers were dried over magnesium sulfate and evaporated to dryness The resulting crude product was purified by column chromatography (silica 15-40 μm (8g) dichloromethane then dichloromethane / methanol 99 1 to 98 2) to provide the expected compound (125 mg, 55%) The product thus obtained showed the following characteristics HRMS calcd for C 30 H 42 NO 9 [M + H] + 560 2860, obsd 560 2863 IR (film ) (cm "1 ) 3516 (OH), 3427 (OH), 1741 (C0 2 ), 1656 (C=C-O), 1504 (Ar), 1224 (C-O), 1 183 (C-O), 11 14 (C-O), 1083 (C-O), 1035 (C-O), 91 1 1 H NMR 400 MHz (CDCI 3 ) (δ ppm, J Hz) 6 62 (1 H, s, H-17*), 6 55 (1 H, s, H-14*), 5 98 (1 H, d, J 3 . 4 = 9 7, H-3), 5 86 (2H, m, OCH 2 0), 5 05 (1 H, s, H-1 ), 4 02 (2H, m, OCH 2 CH 3 ), 3 78 (1 H, d, J 4 3 = 9 7, H-4), 3 68 (3H, s, OCH 3 ), 3 53 (1 H, s, 2'-OH), 3 10 (2H, m, H-11 β+ H~8α), 2 96 (1 H, m, H-10α), 2 60 (2H, m, H-8β + H-10β), 2 38 (1 H, m, H~11α), 2 24 and 1 90 (2H, 2d, J AB = 16 2, CH 2 C0 2 ), 2 02 (1 H, m, H-6 A ), 1 90 (1 H, m, H-6 B ), 1 76 (2H, m, CH 2 -7), 1 5 - 1 15 (6H, m, 3*CH 2 ), 1 21 (3H, t, J = 7 2, OCH 2 CH 3 ), 1 19 (6H, 2s, 2 χ CH3) 2°) Method B Sodium hydride 60% (2 4 mg, 0 1 mmol) was added to a solution of homoharπngtonine (300 mg, 0 55 mmol) in dry ethanol (30 ml) and the resulting mixture was stirred at ambient temperature for 27 hours After addition of water (10 ml) the resulting aqueous layer was saturated with sodium chloride and extracted with dichloromethane (3 x 20 ml) The combined organic layers were dried over magnesium sulfate and evaporated to dryness The crude product thus obtained was purified by phase-reversed chromatography (octadecylsilane 12 μm (65 g), buffer NH CI-HCI / methanol, 82 18) After removal of methanol in vacuo the resulting aqueous layer was alkalinized to pH 8-9 and extracted with dichloromethane (3 x 50 ml) The combined organic layers were dried over magnesium sulfate and evaporated to dryness to provide the expected compound (298 mg, 97%) The product thus obtained showed identical characteristics to this obtained with method A Example 26 Preparation of (2 S)-4øsopropyl-4'-demethyl-epι-homohamnqtonine To a stirred solution of 4'-ιsopropyl-4'-demethyl-anhydro-epι- homoharπngtonine (46 mg, 0 083 mmol) resulting from Example 5 in dry dichloromethane (0 23 ml) under nitrogen Was added at -10°C a commercial solution of hydrobromic acid in acetic acid (0 148 ml, 0 745 mmol, HBr 30% w/w) After stirring at -10°C for 3 hours, was added water (2 2 ml) and the temperature was raised to 20°C After stirring at 20°C for 3 hours, was added a sodium carbonate solution (0 76 M, 4 ml) up to pH 8 The resulting aqueous layer, after saturation with sodium chloride, was extracted with dichloromethane (3 x 5 ml) and the combined organic layers were dried over magnesium sulfate and evaporated to dryness to provide the expected compound (30 mg crude, 64%) The crude product thus obtained showed the following characteristics 1 H NMR 400 MHz (CDCl 3 ) (δ ppm, J Hz) 6 64 (1 H, s, H-17*), 6 59 (1 H, s, H-14*) 5 94 and 5 85 (2H, 2d, J AB = 1 3, OCH 2 0), 5 93 (1 H, d, J 3 4 = 9 8, H-3), 5 03 (1 H, s, H-1), 4 98 (1 H, m, J = 6 2, OCH(CH 3 ) 2 ), 3 78 (1 H, d, J 4 . 3 = 9 7, H-4), 3 65 (3H, s, OCH 3 ), 3 54 (1 H, s, 2'-OH), 3 09 (2H, m, H-1 1 β + H-8α), 2 94 (1 H, m, H-10α), 2 57 and 2 49 (2H, 2d, J AB = 16 6, CH 2 C0 2 ), 2 56 (2H, m H-8β + H-10β), 2 38 (1 H, dd, J AB = 14 0, J = 7 0, H- 1 1α), 2 02 (1 H, m, H-6 A ), 1 89 (1 H, m, H-6 B ), 1 71 (2H, m, CH 2 -7), 1 5 - 0 6 (6H, m, 3 χ CH 2 ), 1 22 and 1 21 (6H, 2d, J = 6 2, OCH(CH 3 ) 2 ), 1 16 (3H, s CH 3 ), 1 15 (3H s, CH 3 ) Example 27 Preparation of (2'R)-4'-ιsopropyl-4'-demethyl-homohamnqtonιne 1°) Method A To a stirred solution of 4'-isopropyl-4'-demethyl-anhydro-homoharrιngtonιne (220 mg, 0,36 mmol) resulting from Example 6 in dry dichloromethane (1 ml) under nitrogen was added at -10°C a commercial solution of hydrobromic acid in acetic acid (0 64 ml, 3 24 mmol, HBr 30% w/w) After stirring at -10°C for 3 hours, was added water (9 5 ml) and the temperature was raised to 20°C After stirring at 20°C for 3 hours, was added a sodium carbonate solution (0 76 M, 17 4 ml) up to pH 8-9 The resulting aqueous layer, after saturation with sodium chloride, was extracted with dichloromethane (3 x 20 ml) and the combined organic layers were dried over magnesium sulfate and evaporated to dryness. The resulting crude product was purified by column chromatography (silica 15-40 μm (6g), dichloromethane then dichloromethane / methanol, 99 1 to 97 3) to provide the expected compound (103 mg, 50%) The product thus obtained showed the following characteristics HRMS calcd for C31 H 44 NO g [M + H 574 3016, obsd 574 3012 IR (film ) (cm "1 ) 3519 (OH), 3430 (OH), 1735 (C0 2 ), 1655 (C=C-O), 1504 (Ar) 1224 (C-O), 1 182 (C-O), 1109 (C-O), 1039 (C-O), 910 1 H NMR 400 MHz (CDCI 3 ) (δ ppm, J Hz). 6.63 (1 H, s H-17*), 6 56 (1 H, s, H-14 * ), 5 96 (1 H, d, J 3 . 4 = 9 8, H-3), 5 86 (2H, s, OCH 2 0), 5 05 (1 H, s, H-1 ), 4 88 (1 H, m, J = 6 2, OCH(CH 3 ) 2 ), 3 78 (1 H, d J 4 . 3 = 9 8, H-4), 3 68 (3H, s, OCH 3 ), 3.54 (1 H, s, 2'-OH), 3 10 (2H, m, H-1 1 β + H-8α), 2.95 (1 H m, H-10α), 2 60 (2H, m H-8β + H-10β) 2 38 (1 H, dd, J AB = 14 0, J = 6.7, H-11 α), 2 19 and 1 87 (2H, 2d, J AB = 16.0 CH 2 C0 2 ), 2 02 (1 H, m, H-6 A ), 1 91 (1 H, m, H-6 B ), 1 76 (2H, m, CH 2 -7), 1 5 - 1 16 (6H, m, 3 χ CH 2 ), 1 18 (12H, m, 2°) Method B Sodium hydride 60 % (13 mg, 0 325 mmol) was added (in 2 parts, at t = 0 and t = 16 hours) to a solution of homoharπngtonine (440 mg, 0 807 mmol) in isopropanol (6 ml) with stirring at ambient temperature under argon 4 hours after the last addition the mixture was adjusted to pH 1 9 by addition of hydrochloric acid 0 1 N (157 ml) and the aqueous layer was washed with ether (3 x 8 ml) The resulting aqueous layer was alkalinized with ammonia 25% (0 3 ml) and was extracted with dichloromethane (8 x 8 ml) The combined organic layers were dried over magnesium sulfate and evaporated to dryness (31 1 mg crude, 67%) The crude product thus obtained was purified by phase-reversed chromatography (octadecylsilane 12 μm (100 g), buffer pH 3 / methanol, 61 39) After removal of methanol in vacuo the resulting aqueous layer was alkalinized to pH 10 with ammonia 25% and extracted with dichloromethane (6 ^ 8 ml) The combined organic layers were dried over magnesium sulfate and evaporated to dryness to provide the expected compound (143 mg 31 %) The product thus obtained showed identical characteristics to this obtained with method A Example 28 Preparation of (2'S)-4'-benzyl-4'-demethyl-ephhomohamnqtonιne To a stirred solution of 4 -benzyl-4 -demethyl-anhydro-epi- homoharπngtonine (28 mg, 0 046 mmol) resulting from Example 7 in dry dichloromethane (0 14 ml) under nitrogen was added at -10°C a commercial solution of hydrobromic acid in acetic acid (83 μl, 0 417 mmol, HBr 30% w/w) After stirring at -10°C for 3 hours, was added water (2 ml) and the temperature was raised to 20°C After stirring at 20°C for 3 hours, was added a sodium carbonate solution (0 76 M, 4 ml) up to pH 8 The resulting aqueous layer, after saturation with sodium chloride, was extracted with dichloromethane (3 x 3 ml) and the combined organic layers were dried over magnesium sulfate and evaporated to dryness to provide the expected compound (30 mg crude, 100%) The crude product thus obtained showed the following characteristics 1 H NMR 400 MHz (CDCI 3 ) (δ ppm, J Hz) 7 34 (5H, m, Ph), 6 64 (1 H, s, H-17), 6 60 (1 H, s, H-14), 5 90 (3H, m, OCH 2 0 + H- 3), 5 12 and 5 07 (2H, 2d, J AB = 12 4, OCH 2 Ph), 5 01 (1 H, s, H-1 ) 3 78 (1 H, d H- 4), 3 60 (3H, s, OCH 3 ), 3 13 (2H, m, H-11 β + H-8α) 2 96 (1 H, m, H-10α), 2 66 and 2 57 (2H, 2d, J AB = 16 7, CH 2 C0 2 ), 2 60 (2H, m, H-8β + H-10β), 2 40 (1 H, m, H-1 1 α), 2 04 (1 H, m, H-6 A ), 1 92 (1 H, m, H-6 B ), 1 78 (2H, m, CH 2 -7), 1 6 - 0 8 (6H, m, 3 χ CH 2 ), 1 16 (3H, s, CH 3 ), 1 15 (3H, s, CH 3 ) Example 29 Preparation of (2'R)-4 , -benzyl-4'-demethyl-homohamnqtonιne 1 °) Method A To a stirred solution of 4'-benzyl-4 -demethyl-anhydro-homoharπngtonine (261 mg, 0 432 mmol) resulting from Example 8 in dry dichloromethane (1 3 ml) under nitrogen was added at -10°C a commercial solution of hydrobromic acid in acetic acid (0.775 ml, 3 89 mmol, HBr 30% w/w) After stirring at -10°C for 3 hours was added water (18 6 ml) and the temperature was raised to 20°C After stirring at 20°C for 3 hours, was added a sodium carbonate solution (0 76 M, 37 ml) up to pH 8 The resulting aqueous layer, after saturation with sodium chloride was extracted with dichloromethane (3 x 20 ml) and the combined organic layers were dried over magnesium sulfate and evaporated to dryness The resulting crude product was purified by column chromatography (silica 15-40 μm (8g) dichloromethane then dichloromethane / methanol, 99 1 to 95 5) to provide the expected compound (80 mg 30%) The crude product thus obtained showed the following characteristics IR (film ) (cm 1 ) 3520 (OH), 3401 (OH), 1744 (C02), 1655 (C=C-0), 1504 (Ar), 1224 (C-O), 1173 (C-O), 1082 (C-O), 1037 (C-O), 910 1 H NMR 400 MHz (CDCI 3 ) (δ ppm, J Hz) 7 33 (5H, m, Ph), 6 62 (1 H, s H-17), 6 44 (1 H, s, H-14), 5 96 (1 H, d, J 3 4 = 9 7, H- 3), 5 77 and 5 65 (2H, 2s, OCH 2 0), 5 09 and 4 94 (2H, 2d J AB = 12 4, OCH 2 Ph) 5 05 (1 H, s, H-1 ), 3 70 (1 H, d, J 4 3 = 10, H-4), 3 68 (3H, s OCH 3 ), 3 52 (1 H, s, 2'- OH), 3 10 (2H, m, H-1 1 β + H-8α) 2 93 (1 H, m, H-10α), 2 59 (2H m, H-8β + H- 10β), 2 40 (1 H, dd, J AB = 14, J = 6 7, H-11σ) 2 31 and 1 92 (2H, 2d, J AB = 16 3, CH 2 C0 2 ), 2 0 (1 H, , H-6 A ), 1 90 (1 H, m, H-6 B ), 1 75 (2H, m CH 2 -7), 1 6 - 1 1 (6H, m, 3 χ CH 2 ), 1 25 (1 H, s, OH), 1 19 (3H, s, CH 3 ), 1 18 (3H, s, CH 3 ) 2)° Method B Sodium hydride 60 % (10 mg, 0 275 mmol) was added to a solution of homoharringtonine (300 mg, 0 55 mmol) in benzylic alcool (4 ml) and the resulting mixture was stirred at ambient temperature for 1 5 hours under argon After adjusting to pH 2 5 by addition of hydrochloric acid 0 1 N (15 ml) the aqueous layer was washed with ether (3 x 15 ml) The resulting aqueous layer was alkalinized with ammonia 25%) (1 5 ml) and was extracted with dichloromethane (6 x 15 ml) The combined organic layers were dried over magnesium sulfate and evaporated to dryness The crude product thus obtained was purified by phase- reversed chromatography (octadecylsilane 12 μm (100 g) buffer pH 3 / methanol 47 53) After removal of methanol in vacuo the resulting aqueous layer was alkalinized to pH 9 with ammonia 25% and extracted with dichloromethane (3 -. 5 ml) The combined organic layers were dried over magnesium sulfate and evaporated to dryness to provide the expected compound (154 mg 45%) The product thus obtained showed the following characteristics Example 30 Preparation of (2 R)-4'-methylthιo-4'-demethoxy-homoharrιnqtonιne To a stirred solution of 4'-methylthιo-4'-demethoxy-anhydro- homoharπngtonine (209 mg, 0 384 mmol) resulting from Example 9 in dry dichloromethane (1 ml) under nitrogen was added at -10°C a commercial solution of hydrobromic acid in acetic acid (0 608 ml, 3 46 mmol, HBr 30% w/w) After stirring at -10°C for 3 hours, was added water (12 2 ml) and the temperature was raised to 20°C After stirring at 20°C for 3 hours, was added a sodium carbonate solution (0 76 M, 29 ml) up to pH 8-9 The resulting aqueous layer, after saturation with sodium chloride, was extracted with dichloromethane (3 x 20 ml) and the combined organic layers were dried over magnesium sulfate and evaporated to dryness The resulting crude product was purified by reversed- phase column chromatography (n-octadecylsilane, 15 μm (20 g), methanol / buffer pH 3, 32 68) and the retained fractions were combined After removal of methanol in vacuo the residual aqueous layer (250 ml) was adjusted to pH 8, extracted with dichloromethane (3 > 80 ml) and the combined organic layers were dried over magnesium sulfate and evaporated to dryness to provide the expected compound (100 mg 46 5%) The crude product thus obtained showed the following characteristics HRMS calcd for C 29 H 40 NO 8 S [M + H] + 562 2475 obsd 562 2477 IR (film ) (cm "1 ) 3513 (OH) 3369 (OH) 1744 (C02), 1688 (COS) 1655 (C=C-O) 1503 (Ar) 1223 (C-O) 1150 (C-O), 1081 (C-O) 1035 (C-O) 91 1 1 H NMR 400 MHz (CDCI 3 ) (δ ppm, J Hz): 6,62 (1 H, s, H-17*), 6.54 (1 H, s, H-14*), 6 01 (1 H, d, J 3 . 4 = 9.7, H-3), 5.87 (2H, s, OCH 2 0), 5.05 (1 H, s, H-1 ), 3 78 (1 H, d, J 4 . 3 = 9.6, H-4), 3.68 (3H, s, OCH 3 ), 3 42 (1 H, s, 2'-OH), 3.09 (2H, m, H-11 β + H-8α), 2.94 (1 H, m, H-10α), 2.59 (2H, m, H- 8β + H-10β), 2.50 and 2.03 (2H, 2d, J AB = 15.8, CH 2 COS), 2,40 (1 H, m, H-1 1 α), 2.23 (3H, s, SCH 3 ), 2.03 (1 H, m, H-6 A ), 1.91 (1 H, m, H-6 B ), 1.76 (2H, m, CH 2 -7), 1.6 - 1.2 (6H, m, 3 χ CH 2 ), 1.19 (3H, s, CH 3 ), 1.18 (3H, s, CH 3 ). Example 31 Preparation of (2'S)-4'-ethylthio-4'-demethoxy-epi-homohamnqtonine : To a stirred solution of 4'-ethylthio-4'-demethoxy-anhydro-epι- homoharringtonine (18 mg, 0.032 mmol) resulting from Example 10 in dry dichloromethane (90 Ol) under nitrogen was added at -10°C a commercial solution of hydrobromic acid in acetic acid (58 μl, 0.29 mmol, HBr 30% w/w). After stirring at -10°C for 3 hours, was added water (2 ml) and the temperature was raised to 20°C. After stirring at 20°C for 3 hours, was added a sodium carbonate solution (0.76 M, 2 ml) up to pH 8. The resulting aqueous layer, after saturation with sodium chloride, was extracted with dichloromethane (3 x 2 ml) and the combined organic layers were dried over magnesium sulfate and evaporated to dryness to provide the expected compound (18 mg crude, 76%), The crude product thus obtained showed the following characteristics: 1 H NMR 400 MHz (CDCI 3 ) (o ppm, J Hz): 6.66 (1 H, s, H-17 * ), 6.59 (1 H, s, H-14*), 5.95 and 5.85 (2H, 2d, J AB = 1.2, OCH 2 0), 5,95 (1 H, d, J 3 . 4 = 9,7, H-3), 5,03 (1 H, s, H-1 ), 3.78 (1 H, d, J 4 . 3 = 9.7, H- 4), 3.66 (3H, s, OCH 3 ), 3 43 (1 H, s, 2'-OH), 3 12 (2H, m, H-1 1 β -i- H-8α), 2.94 (1 H, m, H-10α), 2 89 (2H, m, SCH,CH 3 ), 2 79 (2H, m, CH 2 COS), 2 58 (2H, m H-8β + H-10β), 2 40 (1 H, dd, J AB = 14 2, J = 6 9, H-11α), 2 02 (1 H, m, H-6 A ) 1 90 (1 H m H-6 B ), 1 76 (2H, m, CH 2 -7), 1 5 - 0 6 (6H, m, 3 χ CH 2 ), 1 24 (3H, t, J = 7 4, SCH 2 CH 3 ), 1 16 (3H, s, CH 3 ), 1 15 (3H, s, CH 3 ) Example 32 Preparation of (2'R)-4'-ethylthio-4'-demethoxy-homoharrinqtonine To a stirred solution of 4'-ethylthιo-4'-demethoxy-anhydro- homoharπngtonine (251 mg, 0 45 mmol) resulting from Example 1 1 in dry dichloromethane (1 1 ml) under nitrogen was added at -10°C a commercial solution of hydrobromic acid in acetic acid (0 803 ml, 4 05 mmol, HBr 30%) w/w) After stirring at -10°C for 3 hours, was added water (14 6 ml) and the temperature was raised to 20°C After stirring at 20°C for 3 hours, was added a sodium carbonate solution (0 76 M, 35 9 ml) up to pH 8-9 The resulting aqueous layer, after saturation with sodium chloride, was extracted with dichloromethane (3 x 20 ml) and the combined organic layers were dried over magnesium sulfate and evaporated to dryness The resulting crude product was purified by column chromatography (silica 15-40 μm (8g), dichloromethane then dichloromethane / methanol, 99 5.0 5 to 95 5) to provide the expected compound (120 mg 46%) The product thus obtained showed the following characteristics HRMS calcd for C 30 H 42 NO 8 S [M + H] + 576 2631 , obsd 576 2624 IR (film ) (cm '1 ) 3514 (OH), 3391 (OH), 1744 (C02), 1687 (COS) 1656 (C=C-O) 504 (Ar), 1223 (C-O), 1159 (C-O) 1081 (C-O) 1035 (C-O), 911 1 H NMR 400 MHz (CDCI 3 ) (δ ppm, J Hz) 6 63 (1 H, s, H-17*), 6 54 (1 H, s, H-14*), 5 99 (1 H, d, J 3 4 = 9 8, H-3), 5 97 (2H, s, OCH 2 0), 5 05 (1 H, s, H-1), 3 78 (1 H, d, J 4 3 = 9 8, H-4), 3 67 (3H, s, OCH 3 ), 3 43 (1 H, s, 2'-OH), 3 09 (2H, m, H-11 β + H-8α), 2 94 (1 H, m, H-10α), 2 84 (2H, m, SCH 2 CH 3 ), 2 59 (2H, m, H-8β + H-10β), 2 46 and 1 98 (2H, 2d, J AB = 15 8, CH 2 COS), 2 38 (1 H, dd, J AB = 14 0, J = 6 9, H-1 1 α), 2 02 (1 H, m, H-6 A ), 1 90 (1 H, m, H-6 B ), 1 75 (2H, m, CH 2 -7), 1 5 - 1 1 (6H, m, 3 χ CH 2 ), 1 21 (3H, t, J = 7 5, SCH 2 CH 3 ), 1 19 (3H, s, CH 3 ), 1 18 (3H, s, CH 3 ) Example 33 Preparation of (2'S)-4øsopropylthιo-4'-demethoxy-epι-homohamnqtonιne To a stirred solution of 4'-ιsopropylthιo-4'-demethoxy-anhydro-epι- homoharπngtonine (28 mg, 0 049 mmol) resulting from Example 12 in dry dichloromethane (0 14 ml) under nitrogen was added at -10°C a commercial solution of hydrobromic acid in acetic acid (88 μl, 0 44 mmol, HBr 30% w/w) After stirring at -10°C for 3 hours, was added water (2 ml) and the temperature was raised to 20°C After stirring at 20°C for 3 hours, was added a sodium carbonate solution (0 76 M, 4 ml) up to pH 8-9 The resulting aqueous layer, after saturation with sodium chloride, was extracted with dichloromethane (3 x 3 ml) and the combined organic layers were dried over magnesium sulfate and evaporated to dryness to provide the expected compound (19 mg crude 66%) The crude product thus obtained showed the following characteristics" 1 H NMR 400 MHz (CDCI 3 ) (o ppm J Hz). 6 65 (1 H s, H-17), 6 59 (1 H, s, H-14) 5 94 (1 H, d, J3-4 = 10.0 H-3), 5 94 and 5 88 (2H, 2d, J AB = 1 4, OCH 2 0) 5 03 (1 H, s, H-1), 3 78 (1 H d, J 4 . 3 = 9.7, H-4), 3 66 (3H s, OCH 3 ), 3 64 (1 H, m, C_H(CH 3 ) 2 ), 3 41 (1 H, s, OH), 3 11 (2H, m, H-1 1 β + H-8α), 2 96 (1 H, m, H-10α), 2 77 (2H, m CH 2 COS), 2 59 (2H, m, H-8β + H- 10β) 2 40 (1 H, dd, J AB = 14 2, J = 6 9, H-1 1α), 2 04 (1 H, m, H-6 A ), 1 90 (1 H, m, H-6 B ), 1 76 (2H, m, CH 2 -7), 1 7 - 0 6 (6H, m, 3 χ CH 2 ), 1 29 and 1 27 (6H, 2d, J = 6 8, CH(CH 3 ) 2 ), 1 16 (3H, s, CH 3 ), 1 15 (3H, s, CH 3 ) Example 34 Preparation of (2'R)-4'-ιsopropylthιo-4'-demethoxy-homohamnqtonιne To a stirred solution of 4'-ιsopropylthιo-4'-demethoxy-anhydro- homoharπngtonine (267 mg, 0 467 mmol) resulting from Example 13 in dry dichloromethane (1 1 ml) under nitrogen was added at -10°C a commercial solution of hydrobromic acid in acetic acid (0 839 ml, 4 2 mmol, HBr 30% w/w) After stirring at -10°C for 3 hours was added water (15 6 ml) and the temperature was raised to 20°C After stirring at 20°C for 3 hours, was added a sodium carbonate solution (0 76 M, 38 2 ml) up to pH 8-9 The resulting aqueous layer after saturation with sodium chloride, was extracted with dichloromethane (3 x 20 ml) and the combined organic layers were dried over magnesium sulfate and evaporated to dryness The resulting crude product Was purified by column chromatography (silica 15-40 μm (8g), dichloromethane then dichloromethane / methanol 99 1 ) to provide the expected compound (118 mg, 43%) The product thus obtained showed the following characteristics HRMS calcd for C 31 H 44 NO e S [M + H]' 590 2788 obsd 590 2789 IR (film ) (cm "1 ) 3521 (OH) 3385 (OH) 1743 (C02) 1681 (COS) 1656 (C=C-0) 1504 (Ar), 1223 (C-O) 1 159 (C-O) 1082 (C-O) 1039 (C-O) 910 1 H NMR 400 MHz (CDCI3) (δ ppm, J Hz) 6 64 (1 H, s, H-17), 6 55 (1 H, s, H-14), 5 97 (1 H, d J 3 . 4 = 9 8, H-3), 5 88 (2H s, OCH 2 0), 5 05 (1 H, s, H-1 ), 3 79 (1 H, d, J 4 . 3 = 9 8, H-4), 3 67 (3H, s, OCH 3 ), 3 56 (1 H, m, J = 6 9, CH(CH 3 ) 2 ), 3 44 (1 H, s, 2'-OH), 3 10 (2H, m, H-11 β + H-8α), 2 95 (1 H, td, J = 1 1 1 and 6 8, H-10α), 2 59 (2H, m, H-8β + H-10β), 2 40 and 1 92 (2H, 2d, J AB = 15 6, CH 2 COS), 2 38 (1 H, dd, J AB = 13 9, J = 6 7, H-1 1 α), 2 02 (1 H, m, H-6 A ), 1 90 (1 H, m, H-6 B ), 1 76 (2H, m, CH 2 -7), 1 6 - 1 1 (6H, m, 3 χ CH 2 ) 1 27 and 1 25 (6H, 2d, J = 6 9, CH(CH 3 ) 2 ), 1 18 (6H, 2s, 2 χ CH 3 ) Example 35 Preparation of (2'S)-4'-fe/Ebutylthιo-4'-demethoxy-epι-homoharrιnqtonιne To a stirred solution of 4'-tert-butylthιo-4'-demethoxy-anhydro-epι- homoharπngtonine (60 mg, 0 102 mmol) resulting from Example 14 in dry dichloromethane (0 3 ml) under nitrogen was added at -10°C a commercial solution of hydrobromic acid in acetic acid (0 183 ml, 0 44 mmol, HBr 30% w/w) After stirring at -10°C for 3 hours, was added water (3 ml) and the temperature was raised to 20°C After stirring at 20°C for 3 hours, was added a sodium carbonate solution (0 76 M, 8 6 ml) up to pH 8-9 The resulting aqueous layer, after saturation with sodium chloride, was extracted with dichloromethane (3 x 8 ml) and the combined organic layers were dried over magnesium sulfate and evaporated to dryness to provide the expected compound (30 mg crude, 48%) The crude product thus obtained showed the following characteristics H NMR 400 MHz (CDCI 3 ) (δ ppm, J Hz). 6 65 (1 H, s H-17), 6 59 (1 H, s H-14) 5 96 and 5 89 (2H, 2d, J = 1 3, OCH 2 0) 5.96 (l H, d J 3 4 = 9.9, H-3) 5 03 (1 H, s H-1 ), 3 78 (1 H d J 4 . 3 = 9 7 H-4) 3 66 (3H, s, OCH 3 ), 3 39 (1 H, s, 2'-OH), 3 13 (2H, m, H-11 β + H-8α), 2 96 (1 H, m, H- 10α), 2 74 (2H, m, CH 2 COS), 2 62 (2H, m, H-8β + H-10β), 2 41 (1 H, dd, J AB = 14 0, J = 6 7, H-11α), 2 04 (1 H, m, H-6 A ), 1 91 (1 H, m, H-6 B ), 1 71 (2H, m, CH 2 -7), 1 6 - 0 8 (6H, m, 3 χ CH 2 ), 1 44 (9H, s, C(CH 3 ) 3 ), 1 16 (3H, s, CH 3 ), 1 15 (3H, s, CH 3 ) Example 36 Preparation of (2'R)-4'-ferf-butylthιo-4'-demethoχv-homoharrιngtonιne To a stirred solution of 4'-terf-bUtylthιo-4'-demethoxy-anhydro- homoharπngtonine (216 mg, 0 37 mmol) resulting from Example 15 in dry dichloromethane (1 1 ml) under nitrogen was added at -10°C a commercial solution of hydrobromic acid in acetic acid (0 658 ml, 3 33 mmol, HBr 30% w/w) After stirring at -10°C for 3 hours, was added water (12 6 ml) and the temperature was raised to 20°C After stirring at 20°C for 3 hours, was added a sodium carbonate solution (0 76 M, 31 5 ml) up to pH 8-9 The resulting aqueous layer, after saturation With sodium chloride, was extracted with dichloromethane (3 x 30 ml) and the combined organic layers were dried over magnesium sulfate and evaporated to dryness The resulting crude product was purified by column chromatography (silica 15-40 L m (8g), dichloromethane then dichloromethane / methanol 99 1 to 95 5) to provide the expected compound (70 mg 31 5%) The crude product thus obtained showed the following characteristics HRMS calcd for C 32 H 46 N0 8 S [M + Hf 604 2944, obsd 604 2940 IR (film ) (cm 1 ) 3514 (OH), 3369 (OH), 1744 (C02), 1679 (COS), 1655 (C=C-O), 1504 (Ar) 1223 (C-O) 1159 (C-O), 1081 (C-O), 1035 (C-O) 910 1 H NMR 400 MHz (CDCI 3 ) (δ ppm, J Hz) : 6.65 (1H, s, H-17), 6.54 (1 H, s, H-14), 5.96 (1 H, d, J 3 . 4 = 9.7, H-3), 5.89 (2H, s, OCH 2 0), 5.05 (1 H, s, H-1 ), 3.78 (1 H, d, J 4 . 3 = 9.9, H-4), 3.67 (3H, s, OCH 3 ), 3.46 (1 H, s, 2'-OH), 3.09 (2H, m, H-11 β + H-8α), 2.95 (1 H, m, H-10α), 2.59 (2H, m, H- 8D + H-10β), 2.32 and 1.81 (2H, 2d, J AB = 15.5, CH 2 COS), 2.38 (1 H, m, H-11 α), 2.03 (1 H, m, H-6 A ), 1.91 (1 H, m, H-6 B ), 1.76 (2H, m, CH 2 -7), 1.6 - 1.1 (6H, m, 3 χ CH 2 ), 1.42 (9H, s, C(CH 3 ) 3 ), 1.18 (3H, s, CH 3 ), 1.175 (3H, s, CH 3 ). Example 37 Preparation of (2'R)-4'-(but-2-enyl)-4'-demethyl-homoharringtonine : Sodium hydride 60% (15 mg, 0.366 mmol) was added to a solution of homoharringtonine (500 mg, 0.917 mmol) in crotyl alcohol (1 ml) and the resulting mixture was stirred at ambient temperature for 2.5 hours. After adjusting to pH 4 by addition of hydrochloric acid 1 N the aqueous layer was washed with ether (3 x 10 ml). The resulting aqueous layer was alkalinized with ammonia 25% and was extracted with dichloromethane (3 x 10 ml). The combined organic layers were dried over magnesium sulfate and evaporated to dryness (454 mg crude, 70%). The crude product thus obtained was purified by phase-reversed chromatography (octadecylsilane 12 μm (100 g), buffer pH 3 / methanol, 55:45), After removal of methanol in vacuo the resulting aqueous layer was alkalinized to pH 9.2 with ammonia 25% and extracted with dichloromethane (6 -* 10 ml). The combined organic layers were dried over magnesium sulfate and evaporated to dryness to provide the expected compound (122 mg; 30%), The product thus obtained showed the following characteristics: 1 H NMR 400 MHz (CDCl 3 ) (δ ppm, J Hz) 6 62 (1 H, s, H-17*), 6 54 (1 H, s, H-14*), 5 98 (1 H, d, J 3 4 = 9 8, H-3), 5 86 and 5 85 (2H, 2d, J AB = 1 5, OCH 2 0), 5 74 (1 H, m, H-c) , 5 53 (1 H, m, H-b) , 5 05 (1 H, s, H-1), 4 46 and 4 35 (2H, 2dd, J AB = 12 3, J a b = 6 5, CH 2 -a), 3 77 (1 H, d, J 4 3 = 9 8, H-4), 3 68 (3H, s, OCH 3 ), 3 55 (1 H, s, 2'-0H), 3 10 (2H, m, H-1 1 β+ H-8α), 2 94 (1 H, m, H-10α), 2 58 (2H, m, H-8β + H-10β), 2 38 (1 H, , H-11 α), 2 25 and 1 90 (2H, 2d, J AB = 16 4, CH 2 C0 2 ), 2 02 (1 H, m, H-6 A ), 1 90 (1 H, m, H-6 B ), 1 76 (2H, m, CH 2 -7), 1 72 (3H, dd, J d c = 6 6, J b = 1 2, CH 3 d ) , 1 39 (6H, m, 3 χ CH 2 ), 1 18 (6H, 2s, 2 χ CH 3 ) Example 38 Preparation of (2'S)-4'-(but-2-enyl)-4'-demethyl-epι-homoharrιngtonine Sodium hydride 60% (15 mg 0 366 mmol) was added to a solution of homoharringtonine (500 mg, 0 917 mmol) in crotyl alcohol (5 ml) and the resulting mixture was stirred at ambient temperature for 2 hours After adjusting to pH 4 by addition of hydrochloric acid 1 N the aqueous layer was washed with ether (3 x 10 ml) and diluted with water (50 ml) The resulting aqueous layer was alkalinized to pH 10 6 with ammonia 25% and was extracted with dichloromethane (5 x 15 ml) The combined organic layers were dried over magnesium sulfate and evaporated to dryness (456 mg crude, 78%) The crude product thus obtained was purified by phase-reversed chromatography (octadecylsilane 12 μm (100 g), buffer pH 3 / methanol 65 35) After removal of methanol in vacuo the resulting aqueous layer Was alkalinized to pH 9 5 with ammonia 25% and extracted with dichloromethane (56 ^ 10 ml) The combined organic layers were dried over magnesium sulfate and evaporated to dryness to provide the expected compound (188 mg, 32%) The product thus obtained showed the following characteristics 1 H NMR 400 MHz (CDCI 3 ) (δ ppm, J Hz) 6 64 (1 H, s, H-17*), 6 60 (1 H, s, H-14 * ), 5 94 (1 H, d, J 3 4 = 9 7, H-3), 5 94 and 5 85 (2H, 2d, J AB = 1 2, OCH 2 0), 5 76 (1 H, m, H-c) , 5 54 (1 H, m, H-b) , 5 03 (1 H, s, H-1), 4 49 (2H, m, CH 2 -a), 3 78 (1 H, d, J 4 3 = 9 7, H-4), 3 66 (3H, s OCH 3 ), 3 53 (1 H, s, 2'-OH), 3 10 (2H, m, H-11 β+ H-8α), 2 94 (1 H, m, H-10α), 2 61 and 2 52 (2H, 2d, J AB = 16 7, CH 2 C0 2 ), 2 59 (2H, m, H-8β + H-10β), 2 39 (1 H, dd, J = 14 1 and 6 8, H-11α), 2 02 (1 H, m, H-6 A ), 1 90 (1 H, m, H-6 B ), 1 72 (2H, m, CH 2 -7) and (3H, dd, J d c = 6 5, J d b = 0 9, CH 3 d ) , 1 20 (3H, m, CH 2 ), 1 16 (3H, s, CH 3 ), 1 15 (3H, s, CH 3 ), 1 06 (1 H, m, CH 2 ) 0 93 (1 H, m, CH 2 ), 0 736 (1 H, m, CH 2 ) Example 39 Preparation of (2'R)-4'-(3-methyl-2-butenyl)-4'-demethyl-homoharrιnqtonιne Sodium hydride 60 % (29 4 mg 0 735 mmol) was added to a solution of homoharringtonine (500 mg 0 917 mmol) in 3-methyl-2-butenol (4 ml) and the resulting mixture was stirred at ambient temperature for 1 5 hours under argon After adjusting to pH 2 5 by addition of hydrochloric acid 0 1 N (15 ml) the aqueous layer was washed with ether (3 x 15 ml) The resulting aqueous layer was alkalinized with ammonia 25% (1 5 ml) and was extracted with dichloromethane (6 x 15 ml) The combined organic layers were dried over magnesium sulfate and evaporated to dryness (464 mg crude, 85%) The crude product thus obtained was purified by phase-reversed chromatography (octadecylsilane 12 μm (100 g), buffer pH 3 / methanol 47 53) After removal of methanol in vacuo the resulting aqueous layer was alkalinized to pH 9 with ammonia 25% and extracted with dichloromethane (3 5 ml) The combined organic layers were dried over magnesium sulfate and evaporated to dryness to provide the expected compound (266 mg, 48%) The product thus obtained showed the following characteristics 1 H NMR 400 MHz (CDCI 3 ) (δ ppm, J Hz) 6 62 (1 H, s, H-17), 6 54 (1 H, s, H-14), 5 98 (1 H, d, J 3 4 = 9 8, H-3), 5 86 andt 5 84 (2H, 2d, J = 1 5, 0CH 2 0), 5 28 (1 H, m, H-C=) , 5 05 (1 H, s, H-1), 4 54 and 4 42 (2H, 2dd, J AB = 12 4, J = 7 1 , OCH 2 ), 3 77 (1 H, d, J 4 3 = 9 8, H-4), 3 68 (3H, s, OCH 3 ), 3 54 (1 H, s, 2'-OH), 3 10 (2H, m, H-11 β+ H-8α), 2 94 (1 H, dt, J = 11 5 and 7 0, H-10α), 2 58 (2H, m, H-8β + H-10β), 2 38 (1 H, dd, J AB = 14 0, J = 6 7, H- 11α), 2 24 and 1 89 (2H, 2d, J AB = 16 4, CH 2 C0 2 ), 2 04 (1 H, m, H-6 A ), 1 90 (1 H, m, H-6 B ), 1 77 (2H, m, CH 2 -7), 1 75 (3H, s, CH 3 -C=) , 1 68 (3H, s, CH 3 -C=) , 1 39 (6H, m, 3 χ CH 2 ), 1 19 (3H, s, CH 3 ), 1 18 (3H, s, CH 3 ) Example 40 Preparation of (2'R)-4'-(2-propenyl)-4'-demethyl-homoharπngtonιne Sodium hydride 60 % (29 8 mg, 0.745 mmol) was added to a solution of homoharringtonine (508 mg, 0 932 mmol) in 2-propenol (5 ml) and the resulting mixture was stirred at ambient temperature for 2 hours under argon After adjusting to pH 2 1 by addition of hydrochloric acid 0 1 N (17 ml) the aqueous layer was washed with ether (3 x 15 ml) The resulting aqueous layer was alkalinized with ammonia 25% (1 5 ml) and was extracted with dichloromethane (6 x 15 ml) The combined organic layers were dried over magnesium sulfate and evaporated to dryness (417 mg crude, 78%) The crude product thus obtained was purified by phase-reversed chromatography (octadecylsilane 12 μm (100 g) buffer pH 3 / methanol, 61 5 38 5) After removal of methanol in vacuo the resulting aqueous layer was alkalinized to pH 10 with ammonia 25% and extracted with dichloromethane (5 x 10 ml) The combined organic layers were dried over magnesium sulfate and evaporated to dryness to provide the expected compound (289 mg, 54%) The product thus obtained showed the following characteristics 1 H NMR 400 MHz (CDCI 3 ) (δ ppm, J Hz) 6 62 (1 H, s, H-17), 6 54 (1 H, s, H-14), 5 99 (1 H, d, J 3 4 = 9 8, H-3), 5 87 (1 H, m, HC=), 5 85 (2H, m, OCH 2 0), 5 30 (1 H, m, J = 17 2, =CH 2 ), 5 22 (1 H, m, J = 10 4, =CH 2 ), 5 05 (1 H, s, H-1), 4 53 and 4 42 (2H, 2m, J AB = 13 3, J = 5 6, OCH 2 ), 3 77 (1 H, d, J 4 . 3 = 9 8, H-4), 3 68 (3H, s, OCH 3 ), 3 52 (1 H, s, 2'-OH), 3 10 (2H, m, H- 1 1 β+ H-8α), 2 94 (1 H, dt, J = 11 0 and 6 9, H-10α), 2 59 (2H, m, H-8β + H-10β), 2 38 (1 H, dd, J AB = 14 0, J = 6 7, H-1 1α), 2 28 and 1 90 (2H, 2d, J AB = 16 5, CH 2 C0 2 ), 2 05 (1 H, m, H-6 A ), 1 90 (1 H, m, H-6 B ), 1 75 (2H, m, CH 2 -7), 1 5 - 1 1 (6H, m, 3 χ CH 2 ), 1 29 (1 H, s, 4"-OH), 1 19 (6H, 2s, 2 χ CH 3 ) Example 41 Preparation of (2'R)-4'-(2-methyl-2-propenyl)-4'-demethyl-homoharrιngtonιne Sodium hydride 60 % (23 5 mg 0 470 mmol) was added to a solution of homoharringtonine (400 mg 0 734 mmol) in 2-methyl-2-propenol (4 ml) and the resulting mixture was stirred at ambient temperature for 2 hours under argon After adjusting to pH 2 by addition of hydrochloric acid 0 1 N (15 ml) the aqueous layer was washed with ether (3 x 8 ml) The resulting aqueous layer was alkalinized with ammonia 25% (0 3 ml) and was extracted with dichloromethane (4 8 ml). The combined organic layers were dried over magnesium sulfate and evaporated to dryness (302 mg crude, 70%) The crude product thus obtained was purified by phase-reversed chromatography (octadecylsilane 12 μm (100 g), buffer pH 3 / methanol, 55 45) After removal of methanol in vacuo the resulting aqueous layer was alkalinized to pH 9 8 with ammonia 25% (0 9 ml) and extracted with dichloromethane (5 x 10 ml) The combined organic layers were dried over magnesium sulfate and evaporated to dryness to provide the expected compound (183 mg, 43%) The product thus obtained showed the following characteristics 1 H NMR 400 MHz (CDCI 3 ) (δ ppm, J Hz) 6 62 (1 H, s, H-17), 6 54 (1 H, s, H-14), 5 98 (1 H, d, J 3 4 = 9 8, H-3), 5 85 (2H, s, OCH 2 0), 5 05 (1 H, s, H-1), 4 96 and 4 91 (2H, 2s, =CH 2 ), 4 47 and 4 33 (2H, 2d, J AB = 13 3, OCH 2 ), 3 77 (1 H, d, J 4 . 3 = 9 8, H-4), 3 68 (3H, s, OCH 3 ), 3 51 (1 H, s, 2'-OH), 3 09 (2H, m, H-1 1 β+ H-8α), 2 94 (1 H, dt, J = 1 1 0 and 6 8 H-10α), 2 59 (2H, m, H-8β + H-10β), 2 38 (1 H, dd, J AB = 14 0, J = 6 7, H-11 α), 2 30 and 1 92 (2H, 2d, J AB = 16 5, CH 2 C0 2 ), 2 02 (1 H, m, H-6 A ), 1 90 (1 H, m, H-6 B ), 1 75 (2H, m, CH 2 -7), 1 73 (3H, s, CH 3 -C=), 1 5 - 1 1 (6H, m, 3 χ CH 2 ), 1 19 (6H, 2s, 2 χ CH 3 ) Example 42 Preparation of (2'R)-4'-(2-butynyl)-4'-demethyl-homoharrιnqtonιne Sodium hydride 60 % (30 mg, 0 75 mmol) was added (in 5 parts, at t = 0, t = 1 5, t = 3 5, t = 5 and t = 24 hours) to a solution of homoharringtonine (510 mg, 0 936 mmol) in 2-butynol (2 9 ml) with stirring at ambient temperature under argon 2 hours after the last addition the mixture was adjusted to pH 2 1 by addition of hydrochloric acid 0 1 N (17 ml) and the aqueous layer was washed with ether (3 x 10 ml) The resulting aqueous layer was alkalinized with ammonia 25% (0 3 ml) and was extracted with dichloromethane (6 x 10 ml) The combined organic layers were dried over magnesium sulfate and evaporated to dryness (368 mg crude, 67 5%) The crude product thus obtained was purified by phase- reversed chromatography (octadecylsilane 12 Urn (100 g), buffer pH 3 / methanol, 65 35) After removal of methanol in vacuo the resulting aqueous layer was alkalinized to pH 10 with ammonia 25% (0 4 ml) and extracted with dichloromethane (6 x 8 ml) The combined organic layers were dried over magnesium sulfate and evaporated to dryness to provide the expected compound (171 mg, 46 5%) The product thus obtained showed the following characteristics 1 H NMR 400 MHz (CDCI 3 ) (δ ppm, J Hz) 6 62 (1 H, s, H-17), 6 54 (1 H, s, H-14), 5 99 (1 H, d, J 34 = 9 5, H-3), 5 94 and 5 87 (2H, 2d, J AB = 1 5, OCH 2 0), 5 05 (1 H, s, H-1), 4 60 and 4 48 (2H, 2dq, J AB = 15 2, J = 2 4, OCH 2 ), 3 77 (1 H, d, J 4 3 = 9 8, H-4), 3 67 (3H, s, OCH 3 ), 3 51 (1 H, s, 2'- OH), 3 09 (2H, m, H-1 1 β+ H-8α), 2 94 (1 H, m, H-10α), 2 59 (2H, m, H-8β + H- 10β), 2 38 (1 H, dd, J AB = 13 9, J = 6 7, H-11 ), 2 30 and 1 88 (2H, 2d, J AB = 16 5, CH 2 C0 2 ) 2 02 (1 H, m, H-6 A ), 1 88 (1 H m, H-6 B ), 1 86 (3H, t, J = 2 4, CH 3 -Cs), 1 76 (2H, m, CH 2 -7), 1 5 - 1 1 (6H, m, 3 χ CH 2 ), 1 19 (3H, s, CH 3 ), 1 18 (3H s CH 3 ) Example 43 Preparation of (2'R)-4'-(hexa-2,4-dιenyl)-4'-demethyl-homoharrιnqtonιne Sodium hydride 60 % (8 8 mg, 0 22 mmol) was added to a solution of homoharringtonine (300 mg 0 55 mmol) in (E E)-hexa-1 4-dιenol (3 ml) and the resulting mixture was stirred at 35 °C for 1 h 45 min under argon After adjusting to pH 1.9 by addition of hydrochloric acid 0.1 N (9 ml) the aqueous layer was washed with ether (3 x 6 ml). The resulting aqueous layer was alkalinized to pH 10 with ammonia 25% (0.3 ml) and was extracted with dichloromethane (4 x 6 ml), The combined organic layers were dried over magnesium sulfate and evaporated to dryness (224 mg crude, 67%). The crude product thus obtained was purified by phase-reversed chromatography (octadecylsilane 12 Dim (100 g), buffer pH 3 / methanol, 40:60). After removal of methanol in vacuo the resulting aqueous layer was washed with ether (10 ml), alkalinized to pH 9,5 with ammonia 25% (0.3 ml) and extracted with dichloromethane (6 x 8 ml). The combined organic layers were dried over magnesium sulfate and evaporated to dryness to provide the expected compound (175 mg; 43%). The product thus obtained showed the following characteristics; 1 H NMR 400 MHz (CDCI3) (δ ppm, J Hz): 6,62 (1 H, s, H-17), 6.53 (1 H, s, H-14), 6.22 (1 H, dd, J c . b = 15.2, J c . d = 10.5, H-c), 6,06 (1 H, ddd, J d . e = 15.0, J d . c = 10.6, J d . f = 1.4, H-d), 5.98 (1 H, d, J 3 . 4 = 9.8, H-3), 5.84 and 5,83 (2H, 2d, J AB = 1.5, OCH 2 0), 5.76 (1 H, dq, J e . d = 15,0, J e . f = 6.8, H- e), 5.56 (1 H, dt, J b . c = 15.3, J b . a = 6.6, H-b), 5.05 (1 H, s, H-1 ), 4,53 and 4.42 (2H, 2dd, J AB = 12.8, J a . b = 6,6, CH 2 -a), 3,70 (1 H, d, J 4 . 3 = 9,8, H-4), 3.67 (3H, s, OCH 3 ), 3.52 (1 H, s, 2'-OH), 3.09 (2H, m, H-11 β+ H-8α), 2.94 (1 H, dt, J = 11.5 and 6.9, H-10α), 2.58 (2H, m, H-8β + H-10β), 2.38 (1 H, dd, J AB = 14,0, J = 6.7, H- 11α), 2.26 and 1.88 (2H, 2d, J AB = 16.4, CH 2 C0 2 ), 2.02 (1 H, m, H-6 A ), 1.90 (1 H, m, H-6 B ), 1.77 (3H, d, J ~ 6, CH 3 -f) and (2H, m, CH 2 -7), 1 ,5 - 1 , 1 (6H, m, 3 χ CH 2 ), 1 ,28 (1 H, s, 4 "OH), 1.19 (3H, s, CH 3 ), 1.18 (3H, s, CH 3 ), Example 44 Preparation of (2'R)-4'-(methylcyclopropyl)methyl-4'-demethyl- homoharringtonine ; Sodium hydride 60 % (3 8 mg, 0 095 mmol) was added to a solution of homoharringtonine (263 mg, 0 482 mmol) in (l -methylcyclopropyl)methanol (2 3 ml) and the resulting mixture was stirred at ambient temperature for 20 h under argon After adjusting to pH 2 by addition of hydrochloric acid 0 1 N (9 ml) the aqueous layer was washed with ether (3 x 10 ml) The resulting aqueous layer was alkalinized to pH 9 5 with ammonia 25% (0 3 ml) and was extracted with dichloromethane (6 x 8 ml) The combined organic layers were dried over magnesium sulfate and evaporated to dryness (231 mg crude, 80%) The crude product thus obtained was purified by phase-reversed chromatography (octadecylsilane 12 μm (100 g), buffer pH 3 / methanol, 50 50) After removal of methanol in vacuo the resulting aqueous layer was alkalinized to pH 9 5 with ammonia 25% (0 4 ml) and extracted with dichloromethane (6 8 ml) The combined organic layers were dried over magnesium sulfate and evaporated to dryness to provide the expected compound (173 mg, 69%) The product thus obtained showed the following characteristics 1 H NMR 400 MHz (CDCI3) (δ ppm, J Hz) 662 (1H, s, H-17), 655 (1H, s, H-14), 599 (1H, d, J 34 = 96 H-3), 586 (2H, s, OCH 2 0), 506(1H, s, H-1), 386 and 372 (2H, 2d, J AB = 112, CH 2 -a), 378(1H, d, J 43 = 96, H-4), 368 (3H s, OCH 3 ), 353 (1H, s, 2-OH) 310 (2H m, H-11 β+ H- 8 ), 295 (1H, m H-10u) 258 (2H, m, H-8β + H-10β), 239 (1H, dd, J AB = 140 J = 67, H-11 ex), 2.28 and 195 (2H, 2d, J AB =163, CH 2 C0 2 ) 202 (1H, m, H-6 A ) 190 (1H, m, H-6 B ) 1.76 (2H m, CH 2 -7), 15 - 11 (6H m, 3 χ CH 2 ), 129 (1H, s, 4 "-OH), 119 (6H 2s, 2xCH 3 ), 109 (3H s CH 3 -c), 044 and 0.35 (4H, 2m, CH 2 - d,e). Example 45 Preparation of(-)-cephalotaxyl (2'S)-2-(2,2,2-trιfluoro-ethoxy)carbonylmethyl-6,6- dιmethyl-2-tetrahydropyrane carboxylate or 4'-(2,2,2-trιfluoroethyl)-4'-demethyl- anhydro-epi-homoharπngtonine To a stirred mixture of 4'-dernethyl-anhydro-epι-homoharrιngtonιne (1 g, 1 947 mmol) in dry dichloromethane (10 ml) under argon was added at 0°C triethylamine (dried over potassium hydroxide) (270 μl, 1 947 mmol) and 2,4,6- tπchlorobenzoyl chloride (305 μl, 1 947 mmol) over a period of 10 minutes After stirring at ambient temperature for 2 5 hours a solution of 4-dιmethylamιnopyrιdιne (476 mg, 3 896 mmol) and 2 2,2-trιfluoroethanol (280 μl 3 899 mmol) in dry dichloromethane (3 ml) was added After stirring at ambient temperature for 20 hours, the reaction mixture was diluted with dichloromethane (19 ml) The resulting organic layer was successively washed with water (27 ml), with saturated sodium hydrogen carbonate solution (27 ml), with brine (27 ml) After a last extraction of the combined aqueous layers with dichloromethane (27 ml) the combined organic layers were dried over magnesium sulfate and evaporated to dryness The resulting crude product was purified by column chromatography (silica 15-40 μm (10g), dichloromethane then dichloromethane / methanol, 99 1 to 80 20) to provide the expected compound (838 mg 72%) The product thus obtained showed the following characteristics" 1 H NMR 400 MHz (CDCI 3 ) (ό ppm J Hz) 6 61 (1 H, s, H-14*), 6 57 (1 H s H-17*) 5 83 (3H m, H-3 + OCH 2 0) 5 02 (1 H s, H-1 ) 4 43 and 4 33 (2H, 2dq J AB = 12 7 JH-F = 8 6, OCH 2 CF 3 ) 3 78 (1 H d J 4 . 3 = 9 7 H-4) 3 65 (3H s, OCH 3 ), 3.23 (1 H m H-1 1β), 3 09 (1 H, m, H-8«) 2 94 (1 H, dt, J = 1 1.6 and 7.2, H-10α), 2.60 (2H, m, H-8β + H-10β), 2.39 (1 H,m, H- 1 1α), 2.18 and 1.84 (2H, 2d, J AB = 14.5, CH 2 C0 2 ), 2.01 (1 H, m, H-6 A ), 1.89 (1 H, m, H-6 B ), 1.74 (2H, m, CH 2 -7), 1.5 - 1.2 (6H, m, 3 χ CH 2 ), 1.10 (3H, s, CH 3 ), 1 ,03 (3H, s, CH 3 ). Example 46 Preparation of (2'S)-4'-(2,2,2-trifluoroethyl)-4'-demethyl-epi-homoharringtonine To a stirred solution of 4'-(2,2,2-trifluoroethyl)-4'-demethyl-anhydro-epi- homoharringtonine (300 mg, 0.504 mmol) resulting from Example 45 in dry dichloromethane (1.55 ml) under argon was added at -10°C a commercial solution of hydrobromic acid in acetic acid (0.903 ml, 4.53 mmol, HBr 30% w/w). After stirring at -10°C for 3 hours, was added water (14 ml) and the temperature was raised to 20°C, After stirring at 20°C for 2.75 hours, was added a sodium carbonate solution (0.76 M, 25 ml) up to pH 8,7. The resulting aqueous layer, after saturation with sodium chloride, was extracted with dichloromethane (3 x 1 1.4 ml) and the combined organic layers were dried over magnesium sulfate and evaporated to dryness. The resulting crude product was purified by column chromatography (silica 15-40 μm (15g), dichloromethane / methanol, 99:1 to 90:10) to provide the expected compound (21 1 mg, 68%). The product thus obtained showed the following characteristics: 1 H NMR 400 MHz (CDCl 3 ) (δ ppm, J Hz): 6.65 (1 H, s, H-17*), 6.60 (1 H, s, H-14 * ), 5.94 and 5.85 (2H, 2d, J ΛB = 1.3, OCH 2 0), 5.93 (1 H, d, H-3), 5.05 (1 H, s, H-1 ), 4.53 and 4 32 (2H, 2dq, J AB = 12,6, JH-F = 8.4, OCH 2 CF 3 ), 3.79 (1 H, d, J 4 . 3 = 9,6, H-4), 3 65 (3H, s, OCH 3 ), 3.36 (1 H, s, 2'-OH), 3 08 (2H, m, H-1 1 β H-8α), 2 93 (1 H, m H-10α), 2 70 and 2 64 (2H, 2d, J AB = 16 8, CH 2 C0 2 ), 2 57 (2H, m, H-8β + H-10β), 2 38 (1 H, dd J AB = 14 0, J = 6 8, H-11 α), 2 01 (1 H, m, H-6 A ), 1 89 (1 H, m H-6 B ) 1 76 (2H, m, CH 2 -7), 1 34 (1 H, s, 4"-OH), 1 3 - 1 15 (3H, m, CH 2 ), 1 17 (3H, s, CH 3 ), 1 16 (3H, s, CH 3 ), 1 03 (1 H, m, CH 2 ), 0 97 (1 H, m, CH 2 ), 0 70 (1 H, m, CH 2 ) Example 47 Preparation of(-)-cephalotaxyl (2'R)-2-(2,2,2-tπfluoro-ethoxy)carbonylmethyl- 6,6-dιmethyl-2-tetrahydropyrane carboxylate or 4'-(2,2,2-tπfluoroethyl)-4'- demethyl-anhydro-homoharrinqtonine To a stirred mixture of 4'-demethyl-anhydro-homoharrιngtonιne (723 mg 1 407 mmol) in dry dichloromethane (5 1 ml) under argon was added at 0°C triethylamine (dried over potassium hydroxide) (196 μl, 1 408 mmol) and 2,4,6- tπchlorobenzoyl chloride (220 UI, 1 407 mmol) over a period of 10 minutes After stirring at ambient temperature for 2 5 hours a solution of 4-dιmethylamιnopyrιdιne (344 mg, 2 816 mmol) and 2 2 2-trιfluoroethanol (202 μl 2 813 mmol) in dry dichloromethane (2 2 ml) was added After stirring at ambient temperature for 17 hours, the reaction mixture was diluted with dichloromethane (14 ml) The resulting organic layer was successively washed with water (19 ml) with saturated sodium hydrogen carbonate solution ( 9 ml), with brine (19 ml) After a last extraction of the combined aqueous layers with dichloromethane (19 ml) the combined organic layers were dried over magnesium sulfate and evaporated to dryness The resulting crude product was purified by column chromatography (silica 15-40 ...m (10g) dichloromethane / methanol 99 1 to 90 10) to provide the expected compound (523 mg 77%) The product thus obtained showed the following characteristics 1 H NMR 400 MHz (CDCI 3 ) (δ ppm, J Hz) 6 62 (1 H, s, H-17), 6 58 (1 H, s, H-14), 5 88 (1 H, d, H-3), 5 86 and 5 79 (2H, 2d, J AB = 1 4, OCH 2 0), 5 05 (1 H, s, H-1 ), 4 41 and 4 35 (2H, 2m, OCH 2 CF 3 ), 3 80 (1 H, d, J 4 3 = 9 7, H-4), 3 70 (3H, s, OCH 3 ), 3 12 (2H, m, H-1 1 β) + H-8α), 2 96 (1 H, m, H-10α), 2 60 (2H, m, H-8β + H-10β), 2 37 (1 H, dd, J = 14 1 and 6 7, H- 1 1 α), 2 20 and 1 68 (2H, 2d, J AB = 14 7, CH 2 C0 2 ), 2 01 (1 H, m, H-6 A ), 1 93 (1 H, m, H-6 B ), 1 76 (2H, m, CH 2 -7), 1 7 - 1 2 (6H, m, 3 χ CH 2 ), 1 10 (3H, s, CH 3 ), 1 04 (3H, s, CH 3 ) Example 48 Preparation of (2'R)-4'-(2,2,2-trιfluoroethyl)-4'-demethyl-homoharrιnqtonιne To a stirred solution of 4'-(2,2,2-trιfluoroethyl)-4'-demethyl-anhydro- homoharπngtonine (507 mg, 0 851 mmol) resulting from Example 47 in dry dichloromethane (2 6 ml) under argon was added at -10°C a commercial solution of hydrobromic acid in acetic acid (1 525 ml, 7 659 mmol, HBr 30% w/w) After stirring at -10°C for 3 hours was added water (24 ml) and the temperature was raised to 20°C After stirring at 20°C for 2 75 hours, was added a sodium carbonate solution (0 76 M, 44 ml) up to pH 8 5 The resulting aqueous layer, after saturation with sodium chloride was extracted with dichloromethane (3 x 19 ml) and the combined organic layers were dried over magnesium sulfate and evaporated to dryness (508 mg crude, 97%) The crude product thus obtained was purified by phase-reversed chromatography (octadecylsilane 12 μm (100 g), buffer pH 3 / methanol, 60.40 to 20 80) After removal of methanol in vacuo the resulting aqueous layer was alkalinized to pH 9 6 with ammonia 25% (0 4 ml) and extracted with dichloromethane (12 \ 10 ml) The combined organic layers were dried over magnesium sulfate and evaporated to dryness to provide the expected compound (122 mg, 23%) The product thus obtained showed the following characteristics 1 H NMR 400 MHz (CDCI 3 ) (δ ppm, J Hz) 662 (1H, s, H-17) 655 (1H, s, H-14), 599 (1H, d, J 34 = 97, H-3), 586 and 584 (2H, 2d, J AB = 12, OCH 2 0), 442 and 426 (2H, 2dd, J AB = 127, J H F = 84, OCH 2 CF 3 ), 505 (1H, s, H-1), 378 (1H, d, J 43 = 98, H-4), 368 (3H, s, OCH 3 ), 345 (1H, s, 2'-OH), 310 (2H, m, H-11 β+ H-8α), 296 (1H, m, H-10α), 260 (2H m, H-8β + H-10β), 239 (1H, m, H-11α), 237 and 193 (2H, 2d, J AB = 165, CH 2 C0 2 ), 203 (1H, m, H-6 A ), 192 (1H, m, H-6 B ), 176 (2H, m, CH 2 -7), 155 - 115 (6H, m, 3χCH 2 ), 125 (1H, s, 4"-OH), 119 (6H, 2s, 2 χ CH 3 ) Example 49 Preparation of (2'R)-4'-cyGlopropylmethyl-4'-demethyl-homoharrιnqtonιne Sodium hydride 60 % (3 2 mg, 0 08 mmol) was added to a solution of homoharringtonine (210 mg 0 385 mmol) in cyclopropylmethanol (1 53 ml) and the resulting mixture was stirred at ambient temperature for 2 5 h under argon After adjusting to pH 1 8 by addition of hydrochloric acid 0 1 N (6 ml) the aqueous layer as washed with ether (3 x 5 ml) The resulting aqueous layer was alkalinized to pH 9 5 with ammonia 25% (0 3 ml) and was extracted with dichloromethane (6 x 5 ml) The combined organic layers were dried over magnesium sulfate and evaporated to dryness (175 mg crude 78%) The crude product thus obtained was purified by phase-reversed chromatography (octadecylsilane 12 μm (100 g) buffer pH 3 / methanol 57 43) After removal of methanol in vacuo the resulting aqueous layer was alkalinized to pH 95 with ammonia 25% (04 ml) and extracted with dichloromethane (6 6 ml) The combined organic layers were dried over magnesium sulfate and evaporated to dryness to provide the expected compound (170 mg, 51%) The product thus obtained showed the following characteristics 1 H NMR 400 MHz (CDCI3) (δ ppm, J Hz) 662 (1H, s, H-17), 655 (1H, s, H-14), 598 (1H, d, J 34 = 98, H-3), 587 and 586 (2H, 2d, J AB = 13, OCH 2 0), 506(1H, s, H-1), 383 and 377 (2H, 2dd, J AB = 114, J ab = 13, CH 2 -a), 378 (1H, d, J 43 ~ 10, H-4), 368 (3H, s, OCH 3 ), 355(1H, s, 2'- OH), 310 (2H, m, H-11β+ H-8α), 295 (1H, m, H-10α), 261 (2H, m, H-8β + H- 10β), 239(1H, dd J AB = 141, J = 68, H-11α), 227 and 193 (2H, 2d, J AB = 163 CH 2 C0 2 ), 203 (1H, m, H-6 A ), 193 (1H, m, H-6 B ), 176 (2H, m, CH 2 -7), 15- 11 (6H, m, 3 χ CH 2 ), 119 (3H, s CH 3 ), 118(3H, s, CH 3 ),106 (1H, m, H-b) 055 and 024 (4H, 2m, CH 2 -c,d) Example 50 Preparation of (2'R)-4'-butyl-4'-demethyl-homoharrιngtonιne Sodium hydride 60 % (495 mg, 0124 mmol) was added to a solution of homoharringtonine (225 mg 04125 mmol) in n-butanol (225 ml) and the resulting mixture was stirred at ambient temperature for 20 hours under argon After adjusting to pH 19 by addition of hydrochloric acid 01N (6 ml) the aqueous layer was washed with ether (3 x 6 ml) The resulting aqueous layer was alkalinized to pH 10 ith ammonia 25% (043 ml) and was extracted with dichloromethane (10 x 8 ml) The combined organic layers were dried over magnesium sulfate and evaporated to dryness (178 mg crude, 74%) The crude product thus obtained was purified by phase-reversed chromatography (octadecylsilane 12 μm (100 g), buffer pH 3 / methanol, 50 50) After removal of methanol in vacuo the resulting aqueous layer was alkalinized to pH 9 5 with ammonia 25% (0 4 ml) and extracted with dichloromethane (8 x 10 ml) The combined organic layers were dried over magnesium sulfate and evaporated to dryness to provide the expected compound (107 mg, 44%) The product thus obtained showed the following characteristics 1 H NMR 400 MHz (CDCI3) (δ ppm, J Hz) 662 (1H, s, H-17), 655 (1H, s, H-14), 598 (1H, d, J 34 = 97, H-3), 586 (2H, s, OCH 2 0), 505 (1H, s, H-1), 402 and 392 (2H, 2dt, J AB = 108, J a . b = 68, CH 2 -a), 378 (1 H, d, J 43 = 98, H-4), 368 (3H, s, OCH 3 ), 352 (1 H, s, 2'-OH), 311 (2H, m, H-11β+H-8α), 295(1H, m, H-10α), 260 (2H, m, H-8β + H-10β), 239 (1H, dd, J = 141 and 68, H-11α), 225 and 192 (2H, 2d, J AB = 163, CH 2 C0 2 ), 203 (1H, m, H-6 A ), 192 (1H, m, H-6 B ), 176 (2H, m, CH 2 -7), 155 (2H, m, CH 2 -b), 145 - 115 (8H, m, CH 2 -c and 3 χ CH 2 ), 119 (3H, s, CH 3 ), 118 (3H, s, CH 3 ), 092 (3H, t J = 73, CH 3 -d) Example 51 Preparation of (2'R)-4'-propyl-4'-demethyl-homoharrιnqtonιne Sodium hydride 60 % (8 9 mg, 0 223 mmol) was added to a solution of homoharringtonine (405 mg, 0 742 mmol) in n-propanol (4 ml) and the resulting mixture was stirred at ambient temperature for 1 5 h under argon. After adjusting to pH 1 9 by addition of hydrochloric acid 0 1 N (12 ml) the aqueous layer was washed with ether (3 x 8 ml) The resulting aqueous layer was alkalinized to pH 9 6 with ammonia 25% (0 8 ml) and was extracted with dichloromethane (6 x 10 ml) The combined organic layers were dried over magnesium sulfate and evaporated to dryness (374 mg crude, 88%) The crude product thus obtained was purified by phase-reversed chromatography (octadecylsilane 12 μm (100 g) buffer pH 3 / methanol, 62 38 to 50 50) After removal of methanol in vacuo the resulting aqueous layer was alkalinized to pH 9 5 with ammonia 25% (0 8 ml) and extracted with dichloromethane (6 x 10 ml) The combined organic layers were dried over magnesium sulfate and evaporated to dryness to provide the expected compound (244 mg, 57%) The product thus obtained showed the following characteristics 1 H NMR 400 MHz (CDCI 3 ) (δ ppm, J Hz) 662 (1H, s, H-17), 654 (1H, s, H-14), 598 (1H, d, J 34 = 97, H-3), 586 (2H, s, OCH 2 0), 505 (1 H, s, H-1 ), 397 and 389 (2H, 2dt, J AB = 106, J a b = 68, CH 2 -a), 378 (1H, d, J 43 = 98, H-4), 368 (3H s, OCH 3 ), 352 (1H, s, 2'-OH), 310 (2H, m H-11β+H-8α),294(1H, m, H-10α), 260 (2H, m, H-8β + H-10β), 238 (1H, dd, J = 140 and 67, H-11α), 225 and 192 (2H, 2d, J AB = 163, CH 2 C0 2 ), 202 (1H, m, H-6/ , 190 (1H, m, H-6 B ), 176 (2H m, CH 2 -7), 160 (2H, m, CH 2 -b), 15 - 11 (6H m, 3 χ CH 2 ), 119 (3H s, CH 3 ), 118 (3H, s, CH 3 ) 091 (3H, t, J = 74, CH 3 -c) Example 52 Preparation of (2'R)-4'-ιsobutyl-4'-demethyl-homoharrιngtonιne Sodium hydride 60 % (8 8 mg, 0 220 mmol) was added to a solution of homoharringtonine (3975 mg 0 7282 mmol) in iso-butanol (4 ml) and the resulting mixture was stirred at ambient temperature for 1 5 h under argon After adjusting to pH 1 8 by addition of hydrochloric acid 0 1 N (1 1 ml) the aqueous layer was washed with ether (3 x 8 ml) The resulting aqueous layer was alkalinized to pH 9 7 with ammonia 25% and was extracted with dichloromethane (6 x 10 ml) The combined organic layers were dried over magnesium sulfate and evaporated to dryness (316 mg crude, 768%) The crude product thus obtained was purified by phase-reversed chromatography (octadecylsilane 12 μm (135 g), buffer pH 3 / methanol, 50 50) After removal of methanol in vacuo the resulting aqueous layer was alkalinized to pH 9 5 with ammonia 25% and extracted with dichloromethane (6 10 ml) The combined organic layers were dried over magnesium sulfate and evaporated to dryness to provide the expected compound (254 mg, 61 %) The product thus obtained showed the following characteristics 1 H NMR 400 MHz (CDCI 3 ) (δ ppm, J Hz) 6 62 (1 H, s, H-17), 6 55 (1 H, s, H-14), 5 98 (1 H, d, J 3 4 = 9 5 H-3) 5 86 (2H, s, OCH 2 0), 5 06 (1 H, s, H-1 ), 3 81 and 3 71 (2H, 2dt, J AB = 10 7, J a b = 6 7, CH 2 -a) . 3 78 (1 H, d, J 4 3 = 9 5, H-4), 3 68 (3H, s, OCH 3 ), 3 52 (1 H, s, 2'-OH), 3 1 1 (2H, m, H-1 1 β+ H-8α), 2 94 (l H, m H-10α), 2 60 (2H, m, H-8β + H-10β), 2 38 (1 H, dd, J = 14 1 and 6 8, H-11α), 2 26 and 1 94 (2H, 2d, J AB = 16 3, CH 2 C0 2 ), 2 04 (1 H, m, H-6 A ), 1 90 (1 H, m, H-6 B ), 1 85 (1 H, m, H-b), 1 76 (2H, m, CH 2 -7), 1 5 - 1 15 (6H, m, 3 χ CH 2 ), 1 19 (6H, 2s, 2xCH 3 ), 0 91 (3H, d, J c b = 6 8 CH 3 -c), 0 90 (3H, d, J d b = 6 8, CH 3 -d) Example 53 Preparation of (2'R)-4'-(hex-4-enyl)-4'-demethyl-homoharrιnqtonιne Sodium hydride 60 % (10 96 mg, 0 274 mmol) was added to a solution of homoharringtonine (374 mg 0 685 mmol) in 4-hexenol (4 ml) and the resulting mixture was stirred at ambient temperature for 45 mm under argon After adjusting to pH 1 9 by addition of hydrochloric acid 0 1 N (12 ml) the aqueous layer was washed with ether (3 x 8 ml) The resulting aqueous layer was alkalinized to pH 10 with ammonia 25% and was extracted with dichloromethane (6 x 10 ml) The combined organic layers were dried over magnesium sulfate and evaporated to dryness (358 mg crude, 85%) The crude product thus obtained was purified by phase-reversed chromatography (octadecylsilane 12 μm (135 g), buffer pH 3 / methanol, 30 70) After removal of methanol in vacuo the resulting aqueous layer was washed with ether (5 ml), dichloromethane (5 ml), alkalinized to pH 9 5 with ammonia 25% (0 8 ml) and extracted with dichloromethane (6 x 10 ml) The combined organic layers were dried over magnesium sulfate and evaporated to dryness to provide the expected compound (226 mg, 54%) The product thus obtained showed the following characteristics Η NMR 400 MHz (CDCI 3 ) (δ ppm, J Hz) 662 (1H, s, H-17), 654 (1H, s, H-14), 598 (1H, d, J 34 = 97, H-3), 585 (2H, s, OCH 2 0), 542 (2H, m, H-e,d), 505 (1H, s, H-1), 399 and 392 (2H, 2m, CH 2 -a), 378(1H, d, J 43 = 97, H-4), 368 (3H, s, OCH 3 ), 352 (1H, s, 2'-OH), 310 (2H, m H-11β+ H-8α), 294 (1H, m, H-10α), 259 (2H, m, H-8β + H-10β), 238 (1H, dd, J = 140 and 67, H-11α), 224 and 192 (2H, 2d, J AB = 162, CH 2 C0 2 ), 20 (3H, m, H- 6 A and CH 2 -c), 192 (1H, m, H-6 B ), 176 (2H, m, CH 2 -7), 163 (5H, m, CH 2 -b and CH 3 -f) ,15-11 (6H, m, 3 χ CH 2 ), 118 (6H, 2s, 2 χ CH 3 ) Example 54 Preparation of (2'R)-4'-hexyl-4'-demethyl-homoharrιnqtonιne Sodium hydride 60 % (6.6 mg, 0 16 mmol) was added to a solution of homoharringtonine (300 mg, 0 55 mmol) in n-hexanol (3 ml) and the resulting mixture was stirred at ambient temperature for 1 5 hours under argon After adjusting to pH 1 9 by addition of hydrochloric acid 0 1 N (5 ml) the aqueous layer was washed with ether (3 x 10 ml) The resulting aqueous layer was alkalinized to pH 9 5 with ammonia 25% and was extracted with dichloromethane (6 x 10 ml) The combined organic layers were dried over magnesium sulfate and evaporated to dryness The crude product thus obtained was purified by phase-reversed chromatography (octadecylsilane 12 μm (135 g), buffer pH 3 / methanol, 30 70) After removal of methanol in vacuo and ajusting to pH 1 9 by addition of hydrochloric acid 0 1 N (5 ml), the resulting aqueous layer was washed with ether (3x5 ml), alkalinized to pH 9 5 with ammonia 25% and extracted ith dichloromethane (6 x 10 ml) The combined organic layers were dried over magnesium sulfate and evaporated to dryness to provide the expected compound (158 mg, 47%) The product thus obtained showed the following characteristics 1 H NMR 400 MHz (CDCI 3 ) (δ ppm, J Hz) 662 (1H, s, H-17), 655 (1H, s, H-14), 598 (1H, d, J 34 = 98, H-3), 586 (2H, s, OCH 2 0), 505 (1H, s, H-1), 40 and 391 (2H, 2m, CH 2 -a), 378 (1H, d, J 43 = 99, H-4), 368 (3H, s, OCH 3 ), 352 (1H, s, 2'-OH), 310 (2H, m, H-11 β+ H-8α), 294 (1H, m, H-10σ), 260 (2H, m, H-8β + H-10β), 239 (1H, dd, J = 138 and 67, H- 11α), 225 and 192 (2H, 2d, J AB = 162, CH 2 C0 2 ), 217 (1H, m, H-6 A ) 192 (1H, m, H-6 B ), 176 (2H, m, CH 2 -7), 156 (2H, m, CH 2 -b), 1 5 - 11 (12H, m, CH 2 -c,d,e and 3 χ CH 2 ), 119 (3H, s, CH 3 ), 118 (3H, s, CH,), 089 (3H, t, J = 683, CH 3 -f) Example 55 Preparation of (2'R)-4'-(but-2-enyl)-4'-demethyl-harrιnqtonιne Sodium hydride 60% (7 4 mg, 0 188 mmol) was added to a solution of harπngtonine (250 mg, 0 471 mmol) in crotyl alcohol (2 5 ml) and the resulting mixture was stirred at ambient temperature for 2 5 hours After adjusting to pH 4 by addition of hydrochloric acid 1 N the aqueous layer was washed with ether (3 x 10 ml) The resulting aqueous layer was alkalinized with ammonia 25% and was extracted with dichloromethane (3 x 10 ml) The combined organic layers were dried over magnesium sulfate and evaporated to dryness (268 mg crude, 99 50%) The crude product thus obtained was purified by phase-reversed chromatography (octadecylsilane 12 μm (100 g), buffer pH 3 / methanol, 65 35 to 60 40) After removal of methanol in vacuo the resulting aqueous layer was alkalinized to pH 9 2 with ammonia 25%o and extracted with dichloromethane (6 x 15 ml) The combined organic layers were dried over magnesium sulfate and evaporated to dryness to provide the expected compound (157 mg, 58 5%) The product thus obtained showed the following characteristics 1 H NMR 400 MHz (CDCI 3 ) (δ ppm, J Hz) 6 62 (1 H, s, H-17), 6 55 (1 H, s, H-14), 5 98 (1 H, d, J 3 4 = 9 7, H-3), 5 85 (2H, s, OCH 2 0), 5 75 (1 H, dq, J c b = 15 3, J c d = 6 4, H-c) , 5 55 (1 H, dtq, J b c = 15 3, J b a = 6 4, J b d = 1 7, H-b) , 5 07 (1 H, s, H-1), 4 47 and 4 35 (2H, 2dd, J AB = 12 3, J a b = 6 5, CH 2 -a), 3 78 (1 H, d, J 4 . 3 = 9 6, H-4), 3 70 (3H, s, OCH 3 ), 3 63 (1 H, s, 2'-OH), 3 10 (2H, m, H-1 1 β+ H-8α), 2 95 (1 H, m, H-10α), 2 58 (2H, m, H-8β + H-10β), 2 398 (1 H, m, H-1 1α), 2 28 and 1 89 (2H 2d J AB = 16 4, CH 2 C0 2 ), 2 01 (1 H m, H-6 A ), 1 89 (1 H m, H-6 B ), 1 76 (2H, m, CH 2 -7), 1 72 (3H dd, J d . c = 6 6 J d . b = 1 2, CH 3 -d) , 1 60 (3H, m, CH 2 ), 1 25 (1 H, m CH 2 ), 1 17 (3H, s, CH 3 ), 1 14 (3H, s, CH 3 ) Example 56 Preparation of 4-(2-butenyl) (2R)-2-hydroxy-2-(4-hydroxy-4- methylpentyl)sUGCinate of (-)-drupacιne Sodium hydride 60% (14 mg, 0358 mmol) was added to a solution of 4- methyl (2R)-2-hydroxy-2-(4-hydroxy-4-methylpentyl)succιnate of (-)-drupacιne (500 mg, 08 mmol) in crotyl alcohol (45 ml) and the resulting mixture was stirred at ambient temperature for 25 hours After adjusting to pH 4 by addition of hydrochloric acid 1N the aqueous layer was washed with ether (3x 10 ml) The resulting aqueous layer was alkalinized with ammonia 25% and was extracted with dichloromethane (3x 10 ml) The combined organic layers were dried over magnesium sulfate and evaporated to dryness (366 mg crude, 74%) The crude product thus obtained was purified by phase-reversed chromatography (octadecylsilane 12 μm (100 g), buffer pH 3 / methanol, 5743) After removal of methanol in vacuo the resulting aqueous layer was alkalinized to pH 106 with ammonia 25% and extracted with dichloromethane (6 10 ml) The combined organic layers were dried over magnesium sulfate and evaporated to dryness to provide the expected compound (132 mg, 27%) The product thus obtained showed the following characteristics 1 H NMR 400 MHz (CDCI 3 ) (δ ppm J Hz) 665 (1H, s, H-17*), 646 (1H, s, H-14*) 590 and 587 (2H, 2d J AB = 15 OCH 2 0) 579 (1H, m, H-c) , 557 (1H m, H-b) , 523 (1H, d J 34 = 96 H-3) 486 (1H, d, Jn- 10A = 43 H-11) 456 and 4.45 (2H 2dd, J AB = 123, J ab = 66, CH 2 -a), 356 (1H, d, J 43 = 96 H-4) 351 (1H, s, 2'-OH) 341 (3H s, OCH 3 ), 312 (1H, dd, J AB = 132, J 10A11 =49 H-10 A ), 308 (1H, m, H-8α), 297 (1H d, J AB = 131, H- 10 B ) 267 (1H d, J AB = 140, H-1A), 240 (1H ~q, J = 87 H-8β), 229 and 196 (2H, 2d, J AB = 164, CH 2 C0 2 ), 219 (1H, m, H-6 A ), 204 (1H, m, H-6 B ) 19- 11 (8H m CH 2 -7 and 3xCH 2 ), 173 (3H dd, J d c = 65, J d b = 11 CH 3 -d) , 155 (1 H, d, J AB = 140, H-1 B ) 118 (3H s CH 3 ) 116 (3H, s CH 3 ) Example 57 Preparation of 4-(hexa-2,4-dιenyl) (2R)-2-hydroxy-2-(4-hydroxy-4- methylpentyl)succinate of (-)-drupacιne Sodium hydride 60% (6 8 mg, 0 272 mmol) was added to a solution of 4- methyl (2R)-2-hydroxy-2-(4~hydroxy-4-methylpentyl)succιnate of (-)-drupacιne (200 mg, 0 34 mmol) in hexa-2,4-dιenol (2 ml) and the resulting mixture was stirred at ambient temperature for 2 hours After adjusting to pH 1 5 by addition of hydrochloric acid 1 N (7 ml) the aqueous layer was washed with ether (3 x 10 ml) The resulting aqueous layer was alkalinized to pH 9 5 with ammonia 25% and was extracted with dichloromethane (5 x 10 ml) The combined organic layers were dried over magnesium sulfate and evaporated to dryness (182 mg crude, 86%) The crude product thus obtained was purified by phase-reversed chromatography (octadecylsilane 12 μm (100 g), buffer pH 3 / methanol, 40 60) After removal of methanol in vacuo the resulting aqueous layer was adjusted to pH 1 5 with hydrochloric acid 1 N, washed with ether (3x10 ml), alkalinized to pH 10 6 with ammonia 25% and extracted with dichloromethane (5 • >• 10 ml) The combined organic layers were dried over magnesium sulfate and evaporated to dryness to provide the expected compound (50 mg, 23 5%) The product thus obtained showed the following characteristics 1 H NMR 400 MHz (CDCI 3 ) (δ ppm J Hz) 6 65 (1 H, s, H-17*), 6 46 (1 H, s, H-14*), 6 26 (1 H, dd, J c . b = 15 2, J c . d = 10 5, H-c) 6 05 (1 H m, H-d) , 5 88 and 5.85 (2H 2d J AB = 1 3, OCH 2 0) 5 76 (1 H H-e) 5 60 (1 H m, H-b) , 5 23 (1 H d, J 3 . 4 = 9 6, H-3) 4 86 (1 H, d J . 10A = 4.3, H-11) 4 63 and 4 52 (2H 2dd, J AB = 12 9 J a . b = 6 6, CH 2 -a), 3 55 (1 H, d J 4 . 3 = 9 6 H-4), 3 51 (1 H, s 2 -OH), 3 41 (3H s, OCH 3 ), 3 11 (1 H, dd, J AB = 13 3 J 10A .n = 4 9, H- 10 A ), 306 (1H, m, H-8α), 296 (1H, d, J AB = 131, H-10 B ), 266 (1H, d, J AB = 140, H-1A), 242 (1H, m, H-8β), 230 and 196 (2H, 2d, J AB = 165, CH 2 C0 2 ), 219 (1H, m, H-6 A ), 205 (1H, m, H-6 B ), 177 (2H, m, CH 2 -7) and (3H, d, J fe = 62, CH 3 -f) , 16-11 (6H, m, 3xCH 2 ), 155 (1H, d, J AB = 140, H-1 B ), 117 (3H, s, CH 3 ), 116 (3H, s, CH 3 ) Example 58 Preparation of (2'R)-4"-Fluoro-4"-deoxy-homoharrιngtonιne To a stirred solution of homoharringtonine (20 mg, 0037 mmol) in dry dichloromethane (15 ml) under nitrogen was slowly added DAST (25 μl, 0185 mmol) at -40°C After stirring at -20°C for 3 hours as added a saturated sodium hydrogen carbonate solution (2 ml), the resulting aqueous layer was extracted ith dichloromethane (3 x 5 ml) and the combined organic layers were washed with water (5 ml), with brine (5ml), were dried over magnesium sulfate and evaporated to dryness The resulting crude product (13 mg) was purified by column chromatography (silica 15-40 μm (02g), dichloromethane then dichloromethane / methanol, 982) to provide the expected compound (4 mg, 20%) The product thus obtained showed the following characteristics 1 H NMR 400 MHz (CDCI 3 ) (δ ppm J Hz) 663 (1H s, H-17), 654 (1H, s, H-14), 608 (1H d, J 3 . 4 = 93, H-3), 587 and 586 (2H, 2d J AB = 14, OCH 2 0) 504 (1H, s, H-1), 377 (1H d J 4 . 3 = 98, H-4) 367 (3H, s, OCH 3 ) 3.57 (3H, s, OCH 3 ) 339 (1H, s 2'-OH) 310 (2H m, H-11β+ H- 8α), 294 (1H, m, H-10α) 260 (2H , H-8β + H-10β) 238 (1H m J = 14 and 68, H-11σ) 226 and 189 (2H, 2d J AB = 164 CH 2 C0 2 ) 202(1H m, H-6 A ) 191 (1H m H-6 B ), 175 (2H m CH 2 -7) 16-12 (6H m 3 χ CH 2 ), 134 (3H d J H . P = 214 CH 3 ) 128 (3H d J H . F = 214 CH 3 ) Example 59 Preparation of (2'R)-3"-Fluoro-3"-deoxy-harrιnqtonιne To a stirred solution of harnngtonine (50 mg, 0 094 mmol) in dry dichloromethane (3 5 ml) under nitrogen was slowly added DAST (62 μl, 0 47 mmol) at -40°C After stirring at -20°C for 3 hours, was added a saturated sodium hydrogen carbonate solution (5 ml), the resulting aqueous layer was extracted with dichloromethane (3 x 5 ml) The combined organic layers were washed with water (5 ml), with brine (5ml), dried over magnesium sulfate and evaporated to dryness The crude product thus obtained was purified by phase-reversed chromatography (octadecylsilane 12 μm (135 g), buffer pH 3 / methanol, 45 65) After removal of methanol in vacuo the resulting aqueous layer was adjusted to pH 8 6 with ammonia 25% and extracted with dichloromethane (5 x 10 ml) The combined organic layers were dried over magnesium sulfate and evaporated to dryness to provide the expected compound (1 1 mg, 22%) The product thus obtained showed the following characteristics 1 H NMR 400 MHz (CDCI 3 ) (δ ppm, J Hz) 6 63 (1 H, s, H-17), 6 54 (1 H, s, H-14), 6 01 (1 H, d, J 3 4 = 9 8, H-3), 5 87 and 5 856 (2H, 2d J AB = 1 4, OCH 2 0), 5 05 (1 H, s, H-1 ), 3 77 (1 H, d, J 4 . 3 = 9 8 H-4), 3 67 (3H, s, OCH 3 ), 3 57 (3H, s, OCH 3 ), 3 54 (1 H, s 2'-OH), 3 10 (2H, m, H-1 1 β+ H- 8α), 2 94 (1 H, m, H-10α), 2 60 (2H m, H-8β + H-10β) 2 38 (1 H, m, J = 14 and 6 8, H-1 1 α), 2 29 and 1 90 (2H, 2d, J AB = 16 6 CH 2 C0 2 ) 2 03 (1 H, m, H-6 A ) 1 91 (1 H, m, H-6 B ) 1.75 (2H m CH 2 -7), 1 7 - 1 1 (4H, m, 2 χ CH 2 ) 1 30 (3H, d, J H .F = 21 4, CH 3 ), 1 29 (3H, d, J H . F = 21 4 CH 3 ) Example 60 Preparation of (2'S)-4"-Chloro-4"-deoxy-epι-homoharrιnqtonιne To a stirred solution of epi-homoharπngtonine (100 mg, 0 18 mmol) in dry chloroform (2 ml) under nitrogen was added SOCI2 (131 μl, 1 8 mmol) After stirring at ambient temperature for 2 hours, was added a saturated sodium hydrogen carbonate solution (5 ml), the resulting aqueous layer was extracted ith dichloromethane (3 x 5 ml) and the combined organic layers were dried over magnesium sulfate and evaporated to dryness to provide the expected compound (104 mg crude, 100%) The product thus obtained showed the following characteristics 1 H NMR 400 MHz (CDCI 3 ) (δ ppm, J Hz) 6 64 (1 H, s H-17), 6 59 (1 H, s, H-14), 5 95 and 5 87 (2H, 2d J AB = 1 2, OCH 2 0), 5 94 (1 H, d, J 3 . 4 = 9 8, H-3), 5 04 (1 H, s, H-1 ), 3 78 (1 H, d, J 4 3 = 9 7, H-4), 3 67 (3H, s, OCH 3 ), 3 66 (3H, s, OCH 3 ), 3 58 (1 H, s, 2'-OH), 3 1 1 (2H, m, H-1 1 β+ H- 8α), 2 93 (1 H, m, H-10α), 2 62 and 2 54 (2H, 2d, J AB = 16 5, CH 2 C0 2 ), 2 60 (2H, m, H-8β + H-10β), 2 39 (1 H, m, J = 13 9 and 6 6, H-11α), 2 02 (1 H, m, H-6 A ), 1 90 (1 H, m, H-6 B ), 1 76 (2H, m, CH 2 -7), 1 7 - 0 7 (6H, m, 3 χ CH 2 ), 1 53 (3H, s, CH 3 ), 1 52 (3H, s, CH 3 ) Example 61 Preparation of 4-methyl (2R)-2-hydroxy-2-(4-methyl-pent-3-enyl)succinate of (- cephalotaxine To a stirred solution of homoharringtonine (100 mg, 0 18 mmol) in dry pyndine (2 ml) under nitrogen was added POCI3 (170 μl, 1 8 mmol) at -5 °C After stirring at -5 °C for 20 hours and adjusting to pH 0 5 by addition of hydrochloric acid 50% (9 ml) the aqueous layer was washed with ether (3 x 10 ml) The resulting aqueous layer was alkalinized to pH 9 5 with ammonia 25% and was extracted with dichloromethane (5 x 10 ml) The combined organic layers were dried over magnesium sulfate and evaporated to dryness The crude product thus obtained was purified by phase-reversed chromatography (octadecylsilane 12 μm (100 g), buffer pH 3 / methanol 45 55) After removal of methanol in vacuo the resulting aqueous layer was adjusted to pH 1 5 with hydrochloric acid 1 N, washed with ether (3x10 ml), alkalinized to pH 10 6 with ammonia 25% and extracted with dichloromethane (5 x 10 ml) The combined organic layers were dried over magnesium sulfate and evaporated to dryness to provide the expected compound (20 mg, 21 %) The product thus obtained showed the following characteristics 1 H NMR 400 MHz (CDCI 3 ) (δ ppm, J Hz) 6 62 (1 H s H-17), 6 54 (1 H, s, H-14), 6 0 (1 H, d, J 3 4 = 9 8, H-3), 5 88 and 5 83 (2H, 2d J AB = 1 4, OCH 2 0), 5 06 (1 H, s, H-1 ), 5 01 (1 H, m, =CH), 3 78 (1 H, d, J 4 . 3 = 9 8, H-4), 3 68 (3H s, OCH 3 ), 3 58 (3H, s, OCH 3 ), 3 51 (1 H, s, 2'-OH), 3 14 (2H, m, H-1 1 β+ H-8 ), 2 96 (1 H, m, H-10α), 2 39 (2H, m H-8β + H-10β), 2 39 (1 H, m, J = 14 1 and 6 7 H-11σ), 2 27 and 1 89 (2H, 2d J AB = 16 4, CH 2 C0 2 ), 2 1 - 1 9 (3H m CH 2 -6 + CH 2 ), 2 1 - 1 9 (3H, m, CH 2 -7 +CH 2 ) 1 66 (3H s, CH 3 ), 1 56 (3H, s CH 3 ) 1 42 (2H, m CH 2 ) Example 62 Preparation of (2 R)-4'-(4-pentenyl)-4'-demethyl-homoharrιnqtonϊne Sodium hydride 60 % (7 1 mg, 0 177 mmol) was added to a solution of homoharringtonine (322 mg, 0 590 mmol) in 4-penten-1 -ol (3 2 ml) and the resulting mixture was stirred at ambient temperature for 2 hours under argon After adjusting to pH 1 9 by addition of hydrochloric acid 0 1 N (11 ml), the aqueous layer was washed with ether (3 x 6 ml) The resulting aqueous layer was alkalinized with ammonia 25% ( five drops) and was extracted with dichloromethane (6 x 10 ml) The combined organic layers were dried over magnesium sulfate and evaporated to dryness (230 mg crude, 65 %) The crude product thus obtained was purified by phase-reversed chromatography (octadecylsilane 12 μm (135 g), buffer pH 3 / methanol, 50 50) After removal of methanol in vacuo the resulting aqueous layer was washed ith ether (10 ml) and alkalinized to pH 9 5 with ammonia 25% (five drops) and extracted with dichloromethane (6 x 10 ml) The combined organic layers were dried over magnesium sulfate and evaporated to dryness to provide the expected compound (149 mg, 42 %) The product thus obtained showed the following characteristics 1 H NMR 400 MHz (CDCI 3 ) (δ ppm, J Hz) 662 (1H, s, H-17), 654 (1H, s, H-14), 598 (1H, d, J 34 = 98, H-3), 585 (2H s OCH 2 0), 580 (1H, m CH=) 505 (1H, s H-1), 503 (2H, m =CH 2 ), 398 (2H, m, CH 2 -a), 377 (1H, d, J 43 = 98, H-4), 368 (3H, s, OCH 3 ), 352 (1H, s 2'-OH), 312 (2H, m, H-11β+H-8α), 294(1H, dt, J = 112 and 69 H-10α) 258 (2H, m, H-8β + H-10β), 238 (1H, dd, J AB = 140, J = 67, H-11α) 225 and 192 (2H, 2d J AB = 163, CH 2 C0 2 ) 209 (2H, q J = 72 CH 2 -c), 203 (1H m, H-6 A ) 190 (1H, m, H- 6 B ) 175 (2H, , CH 2 -7) 167 (2H, qt, J = 74 CH 2 -b) 150 - 130 (6H, m 3 χ CH 2 ), 129 (1H s 4"-OH) 118 and 119 (6H 2s 2 χ CH 3 ) Example 63 Preparation of (2'R)-4'-(dimethylamino-ethyl)-4'-demethyl-homoharrinq-tonine: Sodium hydride 60 % (5.8 mg, 0.145 mmol) was added to a solution of homoharringtonine (400 mg, 0.733 mmol) in N,N-dimethylethanol (4 ml) and the resulting mixture was stirred at ambient temperature for 2 hours under argon. After adjusting to pH 1 ,5 by addition of hydrochloric acid 0.1 N (20 ml), the aqueous layer was washed with ether (3 x 8 ml). The resulting aqueous layer was alkalinized with ammonia 25% (pH = 8-9) and was extracted with dichloromethane (6 x 10 ml). The combined organic layers were dried over magnesium sulfate and evaporated to dryness (quantitative). The crude product thus obtained was purified by phase-reversed chromatography (octadecylsilane 12 μm (135 g), buffer pH 3 / methanol, 100:0 then 95:5 ; 90:10 ; 80:20). After removal of methanol in vacuo the resulting aqueous layer was washed with ether (10 ml) and alkalinized to pH 9.5 with ammonia 25% and extracted with dichloromethane (6 x 10 ml). The combined organic layers were dried over magnesium sulfate and evaporated to dryness to provide the expected compound (266 mg; 60 %). The product thus obtained showed the following characteristics: H NMR 400 MHz (CDCI 3 ) (δ ppm, J Hz): 6.60 (1 H, s, H-17), 6.54 (1 H, s, H-14), 6,02 (1 H, d, J 3 . 4 = 9.8, H-3), 5.84 (2H, s, OCH 2 0), 5.04 (1 H, s, H-1 ), 4.43 (1 H, ddd, J = 1 1 ,8 , J = 8.0 , J = 4.0 , H-aα), 3.79 (1 H, d, J 4 . 3 = 9.8, H-4), 3.74 (1 H, m, H-aβ), 3.67 (3H, s, OCH 3 ), 3.12 (2H, m, H- 11 β+ H-8α), 2.94 (1 H, dt, J = 11 ,2 and 6.9, H-101 1), 2.58 (2H, m, H-8 ι + H-10ι I), 2.49 (1 H, ddd, J = 12.6, J = 8,0, J = 4.3, H-b! I), 2,37 (1 H, dd, J ΛB = 14,3, J = 6.7, H-11 α), 2.34 (1 H, m, H-6 A ), 2.22 (6H, s, N(CH 3 ),). 2,22 and 2,1 1 (2H, 2d, J AB = 155, CH 2 C0 2 ), 203 (1H, m, H-6 B ), 189 (1H, ddd, J = 121, J = 77, J = 43, H- bβ), 175 (2H, m, CH 2 -7), 150 - 120 (7H, m, 3 χ CH 2 and 4 ** -0H), 119 and 118 (6H, 2s, 2 χ CH 3 ) Example 64 Preparation of (2'R)-4'-nonyl-4'-demethyl-homoharrιngtonιne Sodium hydride 60 % (8 9 mg, 0 223 mmol) was added to a solution of homoharringtonine (405 mg, 0 742 mmol) in n-nonanol (4 ml) and the resulting mixture was stirred at ambient temperature for 3 hours under argon After adjusting to pH 1 3 by addition of hydrochloric acid 0 1 N (13 ml), the aqueous layer was washed with petroleum ether (8 ml) and the resulting organic layer was extracted with hydrochloric acid 0 1 N (5 ml) This was repeated an other time The combinated aqueous layers were washed with ether (8 ml) then were alkalinized to pH 9 6 with ammonia 25% (fifteen drops) and were extracted with dichloromethane (6 x 8 ml) The combined organic layers were dried over magnesium sulfate and evaporated to dryness (400 mg crude, 82%) The crude product thus obtained was purified by phase-reversed chromatography (octadecylsilane 12 μm (135 g) buffer pH 3 / methanol, 20 80) After removal of methanol in vacuo the resulting aqueous layer was alkalinized to pH 9 7 with ammonia 25% and extracted with dichloromethane (6 -< 10 ml) The combined organic layers were dried over magnesium sulfate and evaporated to dryness to provide the expected compound (256 mg- 52%) The product thus obtained showed the following characteristics 1 H NMR 400 MHz (CDCI 3 ) (δ ppm, J Hz) 662 (1H, s, H-17), 654 (1H, s, H-14), 598 (1H, d, J 34 = 98, H-3), 586 (2H s, OCH 2 0), 505(1H, s, H-1), 400 and 391 (2H, 2m, CH 2 -a), 378 (1H, d, J 43 = 98, H-4), 368 (3H, s, OCH 3 ), 352 (1H, s, 2 * -OH), 310 (2H, m, H-11 β+ H-8α), 295 (1H, m, H-10α), 260 (2H, m, H-8β + H-10β), 238 (1H, dd, J = 141 and 67, H- 11α), 224 and 192 (2H, 2d, J AB = 163, CH 2 C0 2 ), 203 (1H, m, H-6 A ), 192 (1H, m, H-6 B ), 177 (2H, m, CH 2 -7), 156 (2H, m, CH 2 -b), 150 - 122 (16H, m, CH 2 - c,d,e,f,g,h and 3 χ CH 2 ), 119 (6H, s, 2 x CH 3 ), 088 (3H, t, J = 68, CH 3 -ι) Example 65 Preparation of (2'R)-4'-pentyl-4'-demethy!-homoharrιngtonιne Sodium hydride 60 % (10 0 mg, 0 250 mmol) was added to a solution of homoharringtonine (416 mg, 0 762 mmol) in n-pentanol (4 2 ml) and the resulting mixture was stirred at ambient temperature for 2 hours under argon After adjusting to pH 1 8 by addition of hydrochloric acid 0 1 N (14 ml) the aqueous layer was washed with ether (3 x 8 ml) The resulting aqueous layer was alkalinized with ammonia 25% (pH = 9 5) and was extracted with dichloromethane (6 x 10 ml) The combined organic layers were dried over magnesium sulfate and evaporated to dryness (339 mg crude, 74%) The crude product thus obtained as purified by phase-reversed chromatography (octadecylsilane 12 μm (130 g) buffer pH 3 / methanol, 40 60) After removal of methanol in vacuo the resulting aqueous layer was alkalinized to pH 9 7 with ammonia 25% and extracted with dichloromethane (6 10 ml) The combined organic layers were dried over magnesium sulfate and evaporated to dryness to provide the expected compound (274 mg, 60%) The product thus obtained showed the following characteristics 1 H NMR 400 MHz (CDCI3) (δ ppm, J Hz) 662 (1H, s, H-17), 655 (1H, s, H-14), (1H, d, J 34 = 97, H-3), 586 (2H, s OCH 2 0), 505 (1H, s, H-1), 400 and 392 (2H, 2m, CH 2 -a), 378 (1H, d, J^ = 92, H-4), 368 (3H, s, OCH 3 ), 353 (1H, s, 2-OH), 312 (2H, m, H-11β+ H-8α), 296 (1H, m, H-10α), 261 (2H, m, H-8β + H-10β), 241 (1H, m, H-11α), 225 and 195 (2H, 2d, J AB = 162, CH 2 C0 2 ), 203 (1H, m, H-6 A ), 192 (1H, m, H-6 B ), 178 (2H, m, CH 2 -7), 157 (2H, m, CH 2 -b), 150 - 122 (10H, m, CH 2 -c,d and 3 χ CH 2 ), 119 (6H, s, 2 x CH 3 ), 090 (3H, t, J = 69, CH 3 -e) Biological data 1 - Materials and methods Structural analogues of harringtonines described in this invention were tested on K562 cell line, derived from chronic myeloid leukemia cells in blastic transformation (bcr-abl positive) The cell line Was purchased from ATCC (American Tissue Culture Collection) and grown in RPMl medium supplemented with 10% heat-inactivated fetal calf serum, 2 mmol/L glutamine, 50 lU/mol penicillin and 50 lU/mol streptomycin All tested products were initially dissolved in 2N HCl (pH=2), supplemented with ultrasound treatment during 1h Working concentrations were made by dilution in culture medium (pH around 7) Cells in exponential growth phase were placed into 96-mιcrowell plates in concentration 3x10 /mL (total volume 200 μL/well) and incubated with drugs for 72h at 37°C in 5% C0 2 humidified atmosphere Following incubation, 20 μL of MTT solution (Sigma, St Louis, MO) was added to each well During the following 6h of incubation at 37°C, the purple formazan product was formed by conversion of the yellow MTT salt in the mitochondria of the viable cells The resulting precipitate was dissolved in DMSO and the amount of converted MTT was quantified in an ELISA reader (MR 5000, Dynatech) Each product was tested in triplicate (3x8 wells) Every test contained at least one plate with HHT as control added in the same concentration as the tested products 2- Results The following table represents the results of some examples of the compounds according to the present invention in K562 cell line compared to the homoharringtonine, the harringtonine and the cephalotaxine. DMHO means 4'-demethyl-hoιnoharringtonιne 2 DMHD means 4 , -demethyl-4"-hydroxydrupangtonine 3 DMHA means 4'-demethyl-harringtonιne 4 HHT means homoharringtonine (natural or semi-synthetic source) 5 CTX means cephalotaxines (natural source) The same method as above was used to test the O-hexadienyl-DMHO (example 43) on K562 MRP , a subline of K562 line exhibiting a strong resistance to 50 ng/mL of homoharringtonine The IC 50 of the 0-hexadιenyl-DMHO (example 43) was 16 ng/mL, I e a value not significantly different from homoharringtonine itself in non resistant version of K562 line (cf above table)

Claims: CLAIMS 1. A compound of formula (I) wherein • W represents O or NH, • Q represents an unbranched or branched, saturated or unsaturated or aromatic, cyclic or acyclic or heterocyclic hydrocarboned radical containing 1 to 30 carbon atoms including or not heteroatom(s), • R 1 is H, OH, OMe, O^d-C^-alky!, O-aryl-(C 1l -C 30 )-alkyl, O-(C 2 -C 30 )-alkenyl, O-(C 3 -C 30 )-cycloalkyl or null and R 2 is H or OH, or R 1 , R 2 form together -0-, R 3 = R 4 = OMe or R 3 and R 4 form together -OCH 2 0-, • R is H, ^-C^alky! or O-protecting group and R 6 represents an unbranched or branched, saturated or unsaturated or aromatic, cyclic or acyclic or heterocyclic hydrocarboned radical containing 1 to 30 carbon atoms including or not heteroatom(s), or R and R 6 form together -CMe 2 -, • n is 0 to 8, R 5 is H, OH, OMe, O-(C 1 -C 30 )-alkyl, O-aryl-(C 1l -C 30 )-alkyl, O-(C 2 -C 30 )-alkenyl, O-(C 3 -C 30 )-cycloalkyl or O-aryl, • the doted line is null or forms a double bond depending on the meaning of R 1 , except for compounds where • W represents O, the doted line forms a double bond, R 1 is null, R 2 is H, R 3 and R 4 represent -O-CH 2 -O-, R 5 is OMe, Q = C0 2 R 7 and 1 °) R = H, R 6 = -(C-OH)Me 2 , n = 2 or 3, R 7 = Me or H, 2°) R = H, R 6 = -(C-H)Me 2 , n = 2 to 4, R 7 = Me, 3°) R = H, R δ = -(C-H)Me 2 , n = 1 or 2, R 7 = H, 4°) R = H, R 6 = Ph, n = 1 to 3, R 7 = Me, 5°) R = H, R 6 = -CH=CH-Ph, n = 0, R 7 = Me, 6°) R = H, R 6 = CH 3 , n = 4, R 7 = Me, 7°) R and R 6 form together -CMe2-, n = 2 or 3, R 7 = Me, • W represents O, the doted line forms a double bond, R 1 is null, R 2 is OH, R 3 and R 4 represent -0-CH2-0-, R 5 is OMe, and R = H, R 6 = -(C-H)Me 2 , n = 2 or 3, R 7 = Me • W represents O, the doted line is null, R1 and R2 represent -0-, R 3 and R 4 represent -0-CH 2 -0-, R 6 is OMe, and R = H, R 6 = -(C-H)Me 2l n = 2, R 7 = Me 2. A compound of formula (I) according to claim 1 wherein • Q = COZ-R 8 , Z = 0, S, or NH, and or Z- R 8 is NR 12 R 13 , R 2 and R 13 representing respectively R 9 and R 10 , R 9 , R 10 , R 11 are independently H, d-C^ alkyl, C 3 -C 30 cycloalkyl, aryl, aryl- (C C 30 )-alkyl, C 2 -C 30 alkenyl, C 2 -C 30 alkynyl, C C 30 trihalogenoalkyl, C-,- C 30 alkylamino-(C -C 30 )alkyl, C C 30 dialkylamino(C C 30 )-alkyl, or amino-(C 1 -C 30 )- alkyl, or where R 14 , R δ , R S are independently H, halogen, C 1 -C 30 alkyl, C 3 -C 30 cycloalkyl, aryl, aryl-(C 1 -C 30 )-alkyl, C 2 -C 30 alkenyl or C 2 -C 30 alkynyl, C Csotrihalogenoalkyl, m is 0 to 4, each of these groups including or not heteroatom(s). 3. A compound of formula (I) according to claim 2 wherein • R s = -(C-Y)Me 2 , -CH=CMe 2 , or an aryl group or R and R 6 form together -CMe 2 -, Y = H, OH or halogen 4 A compound of formula (I) according to claim 3 wherein • the doted line forms a double bond R 1 is null R 2 is H R 3 and R 4 represent -0-CH 2 -0- R 5 is OMe 5 A compound of formula (I) according to claim 3 wherein • the doted line is null • R and R 2 represent -O- R 3 and R 4 represent -0-CH 2 -0- R 5 is OMe 6 A compound of formula (I) according to claim 4 or 5 wherein n = 1 to 3 7 A compounds of formula (I) according to anyone of the claims 1 to 6 wherein W represents O 8 A compound of formula (I) according to claim 7 wherein it is selected from the group consisting of the following compounds 1 to 65 8 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 and 65. 9 A process for preparing a compound of formula (I) according to claim 1 to 8 in the case where W represents O, Q = COZ-R 8 and Z and R 8 are defined as in claim 2 comprising the following steps i) then n), i) hydrolyzing selectively the compound of formula (II) wherein R 1 is H, OH, OMe, O-(C 1 -C 30 )-alkyl, O-aryl-(C 1 -C 30 )-alkyl, O-(C 2 -C 30 )-alkenyl, O-(C 3 -C 30 )-cycloalkyl or null and R 2 is H or OH, or R 1 and R 2 form together -0-, R 3 = R 4 = OMe or R 3 and R 4 form together -OCH 2 0-, R is H, CrC-joalkyl or O-protecting group and R 6 represents an unbranched or branched, saturated or unsaturated or aromatic, cyclic or acyclic or heterocyclic hydrocarboned radical containing 1 to 30 carbon atoms, including or not heteroatom(s), or R and R 6 form together -CMe 2 - n is 0 to 8 R 5 is H, OH, OMe, O-(C 1 -C 30 )-alkyl l O-aryl-(C 1 -C 30 )-alkyl, O-(C 2 -C 30 )-alkenyl, O-(C 3 -C 30 )-cycloalkyl or O-aryl, the doted line is null or forms a double bond depending on the meaning of R 1 Z= O or S ,and R 17 is C,-C 30 alkyl, C 2 -C 30 alkenyl, C 3 -C 30 cycloalkyl, C 2 -C 30 alkynyl aryl-(C,- C 30 )-alkyl or aryl, advantageously methyl or ethyl with an agent such as mineral hydroxide advantageously lithium potassium or sodium hydroxide, in hydro-organic solvent mixture to give as reaction product amphoteric acid of formula (III) wherein R 1 to R 5 , R and R 6 are defined as above n) performing the esterification of the above obtained amphoteric acid of formula (III) with an esterification agent and a compound of formula R 8 -ZH R 8 and Z being defined as in claim 2 and wherein the steps i) and n) are carried out successively or simultaneously 10 The process as described in claim 9 wherein the esterification agent is a lewis acid or a protonic acid 1 1 The process as described in claims 9 and 10 wherein the amphoteric acid of formula (III) is activated ith an imide or by formation of a mixte anhydride or an acid chloride 12 The process as described in claim 11 wherein the imide is dicyclohexylcarbodi-imide or diisopropylcarbodiimide 13 The process as described in claim 11 wherein the mixte anhydride is formed with 2,4 6-trιchlorobenzoιc acid by contact with 2 4 6~trιchlorobenzoyl chloride in the presence of a base 14 The process as described in claim 9 wherein the steps i) and n) are carried out simultaneously without isolation of the amphoteric acid of formula (III) via a reaction of transestenfication performed in presence of an acidic or basic catalyst 15 The process as described in claim 14 wherein the catalyst is a base such as an alkaline hydride 16 The process as described in claim 14 wherein the catalyst is a lewis acid or a protonic acid 17 The process as described in claims 9 to 16 wherein Z is O and R 7 is methyl 18 A pharmaceutical composition which comprises a therapeutically effective amount of at least one compound of anyone of claims 1 to 8 associated with one or more pharmaceutically acceptable carriers 19 The Use of at least one compound of anyone of claims 1 to 8 or of a pharmaceutical composition of claim 18 as chemotherapeutic agent 20 The use of at least one compound of anyone of claims 1 to 8 or of a pharmaceutical composition of claim 18 as enhancer of other chemotherapeutic agents 21 The use of at least one compound of anyone of claims 1 to 8 or of a pharmaceutical composition of claim 18 for inhibiting tumors growth 22 The use of at least one compound of anyone of claims 1 to 8 or of a pharmaceutical composition of claim 18 for inhibiting mammalian parasites 23 The use according to anyone of the claims 19 to 22 on leukemic cell lines exhibiting resistance to other agents in particular harπngtonine 24 The use of at least one compound of anyone of claims 1 to 8 or of a pharmaceutical composition of claim 18 as reversal agent, in particular of harnngtonine 25 A method for treating mammalian tumors which comprises administering to a mammal a therapeutically effective amount of at least one compound of anyone of claims 1 to 8 or a pharmaceutical composition of claim 18

Inventors: BATAILLE PATRICIA, DHAL ROBERT, DROUYE FREDDY, MARIE JEAN-PIERRE, RADOSEVIC NINA, ROBIN JEAN-PIERRE, ROBIN JULIE, SOUCHAUD KARINE, BATAILLE, PATRICIA, DHAL, ROBERT, DROUYE, FREDDY, MARIE, JEAN-PIERRE, RADOSEVIC, NINA, ROBIN, JEAN-PIERRE, ROBIN, JULIE, SOUCHAUD, KARINE
Applicants: ONCOPHARM CORP, ONCOPHARM CORPORATION
Application year: 2000
Main classification: C07D491
IPC codes: A61K31, A61K45, A61P33, A61P35, A61P43, C07D487, C07D491, C07D498