NEW BIOACTIVE TRITERPENOIDS AND SECO-TRITERPENOIDS

Abstract: The new triterpenoids of general formulae (I), (II), (III) and (IV) where R<1> represents a dialkyl, trialkyl, triphenyl, diphenylalkyl, alkyldiphenyl, dialkylphenyl, haloalkyl, halophenylalkyl, allylalkyl or alkylaminoalkyl group and R<2> represents a carboxyl group, salt or ester, and a process for their preparation which comprises reaction of friedelin with a silylating agent in the presence of a bulky strong base, with kinetic or thermodynamic control, to produce regio-specifically compounds of general formula (I) or (II). Oxidation of (I) or (II) yields the corresponding hydroxy ketones (VII) or (VIII), from which acyl and glycosyl derivatives can be prepared, and further oxidation of the hydroxy ketones (VII) or (VIII) with peracid gives the seco-aldehyde acids (III) or (IV), from which esters or salts can be prepared. Ozonolysis of (I) or (II), followed by reductive treatment, produces the diols of formula (IX) or (X), from which acyl and glycosyl derivatives can be prepared. Oxidation of (I) with a benzoquinone leads to friedel-1-en-2-one (XI) in high yields. Compounds or combinations of compounds (I), (II), (III), (IV), (VI), (VII), (VIII), (IX), (X), (XII), including the acyl and glycosyl derivatives thereof, find application in fungicidal, bactericidal, antitumour and antifeedant compositions.

Description: DESCRIPTION NEW BIOACTIVE TRITERPENOIDS AND SECO-TRITERPENOIDS Background of the invention This invention relates to new friedelan triterpenoid derivatives which have application as bioactive agents in fungicidal, bactericidal, antitumour and antifeedant compositions and to processes for preparing them, as well as to new processes for preparing known friedelin derivatives, starting from friedelin obtained from cork smoker wash solids. Cork smoker wash solids are a by-product from the manufacture of cork particle boards, forming when cork granules are subject to compression and treatment with super-heated steam, and it accummulates in the piping as a black waxy material which forces operations to stop periodically for cleaning. Although cork smoker wash solids are a superior source of friedelin V and 3-hydroxyfriedel-3-en-2-one VI (R=H) [E. J. Corey and J. J. Ursprung, J. Amer. Chem. Soc, 1956, 78 , 5041 ; I. Ribas-Marques and J. Fernandez-Salgado, Anal. Quim., 1974, 70, 363] S. K. Talapatra, D. K. Pradhan and B. Talapatra, Indian J. Chem., 1978, 16B, 361], up to the present time no extraction process has been exploited for industrial application and therefore this industrial waste has found no use, being usually destroyed by incineration. The application of friedelin V has been described for the treatment of bladder cancer [H. C. Simon, German Patent 25 08 338, 19 Feb. 1976] and cachexia due to SUBSTITUTE SHEET carcinoma, sarcoma and leukemia [H. C. Simon, US Patent 4,444,791, 24 Apr. 1984]. Its anticonvulsive, anti-inflamatory [A. K. Chaturvedi, S.S. Parmar, S. C. Bhatnagar, G. Mistra and S. K. Nigam, Res. Commun. Chem. Pathol. Pharmacol. , 1974, 9, 11] and antidiuretic activities have been described [S. H. Rizvi, A. Shoeb, R. S. Kapil and S. P. Popli, Experientia, 1980, 36, 146]. Friedelin V has been reported to exhibit antifeedant activity for Spodoptera littoralis [M. A. Abbassy, A. El-Shazli and F. El-Gayar, Z. Angew. Entomol., 1977, 83, 317] and Anthonomus grandis [D. H. Miles, A. M. Ly, S. A. Randle, P. A. Hedin and M. L. Burks, J. Agric. Food Chem., 1987, 35, 794], but these results were not confirmed by our own assay tests. Moreover, there are no references to the use of the new and known friedelin derivatives of the present invention as bioactive agents. Accordingly, what is needed in the art is an efficient process for the isolation of friedelin from cork smoker wash solids and processes for its high yield transformation into new derivatives, or known derivatives from other sources unavailable up to the present in limited quantities, for application as effective bioactive agents. Quite surprinsigly, the present invention fulfills these needs. SUBSTITUTE SHEE1 Summary of the invention The present invention relates to new triterpenoids, including silyl enol ethers and seco-triterpenoids, and to new processes for making them as well as to make several known triterpenoids, namely α,β-unsaturated and polyhydroxylated systems, through hemisynthesis in a reduced number of steps and in high yields using friedelin V as the starting material, obtained from cork smoker wash solids as the preferred raw material. The derivatives of the present invention have higher or diverse activity in relation to friedelin, and can be used as fungicidal, bactericidal, antitumour or antifeedant agents. The present invention also describes an efficient process for the joint extraction of friedelin V and 3-hydroxyfriedel-3-en-2-one VI (R=H) from cork smoker wash solids and their separation, thereby making viable the use of an industrial waste as a raw material for the production of new compounds with biological activity and of known substances, up to now unavailable in good yields, also possessing biological activity. Description of the Specific Embodiments This invention comprises the new friedelin derivatives of general formulae I, II, III and IV SUBSTITUTE SHEET (III) (IV) wherein R 1 represents a dialkyl, trialkyl, triphenyl, diphenylalkyl, alkyldiphenyl, dialkylphenyl, haloalkyl, allylalkyl or alkylaminoalkyl group and R2 represents a carboxyl group, salt or ester. The processes of the present invention provide the compounds of general formula I and II, which are produced from friedelin V by regio-specific silylation in no less than 85% yield, by reaction in basic medium with a bulky strong base and a silylating agent; time and temperature control determines the formation of the kinetic or thermodinamic product, to yield, respectively, the new silyl enol ethers I or II. The present process for the production of I and II is a significant improvement over earlier methods for a number of reasons which include: (1) although the process has been previously described, it was only applied to straight chain ketones up to 7 carbon atoms and for camphor [J. Dedeier, P. Gerval and E. Frainnet, J. Organonetal. SUBSTITUTE SHEET - Chem., 1980, 185, 183] and (2) in spite of the fact that silylation of steroidal ketones with trimethylsilyl chloride in the presence of lithium isopropylamide in good yields has been described [see, for example, I. Fleming and I.Paterson, Synthesis, 1979, 736; M. Anastasia, P. Allevi, P. Ciuffreda, A. Fiecchi and A. Scale, J. Chem. Soc. Perkin Trans. I, 1986, 2117], friedelin V reacts with difficulty under such conditions and yields are not greater than 50%. According to the process of the present invention, to achieve α-hydroxylation of friedelin V, the enol silyl ethers I or II are used as intermediates to yield, respectively, 2θ!-hydroxyfriedelan-3-one (VII ,R3=H, cerine) or 4α-hydroxyfriedelan-3-one (VIII, R3=H) (VI I ) (VI I I ) in yields higher than 60%, and is based on the formation of α-ketols using catalytic amounts of osmium tetroxide in the presence of a stoicheometric oxidant [see, for example, J. P. McCormick, W. Tomasik and M. W. Johnson, Tetrahedron Lett., 1981 , 22, 607]. The process for the production of cerine VII by α-hydroxylation of friedelin V according to the present invention is a significant improvement over an earlier method SUBST ITI ITF Xi L t - 6 as described by G. Gutta and S. N. Bose, Indian J. Chem., 1989, 28B, 975, where cerine VII was produced in ca. 20% by oxidation of friedelin V with lead tetraacetate followed by hydrolysis. Moreover, it is worth noting that cerine VII does not occur in cork smoker wash solids and is found only as traces in cork powder [see, for example, M. L. Mata, Identificaςao dos Constituintes Quimicos do Pό da Cortiςa e sua Valorizaςao por Hemissintese, M.Sc. Dissertation, Mestrado em Qulmica Organica Tecnolόgica, Universidade Nova de Lisboa, Lisboa, 1991], and therefore the present process makes this known product readily available. According to the processes of the present invention, to prepare the new seco-acids of formula III (R 2 =H) or IV (R2=H) (III) (IV) in quantitative yield, compounds VII or VIII are made to react with periodic acid [see, for example, M. Anastasia, P. Allevi, P. Ciuffreda, A. Fiecchi and A- Scala, J. Chem. Soc. Perkin Trans. I, 1986, 2117] and can, by reaction with alcohols or bases, according to methods well known to those skilled in the art, yield the corresponding seco-esters or salts. Although the conversion of friedelanones into seco-friedelanes has been described by A. Patra and S. K. Chaudhuri, Indian J. Chem., 1989, 28 B, 376, in the case of friedelin V and due to its low reactivity, 3,4-seco-friedelane-3,4-lactone was formed in yields not greater than 3% and there SUBSTITUTE SHEET are no other reports of synthetic pathways leading to higher yields of seco-acids. According to the present invention, the diols of formulae IX and X (R 4 =H) are prepared in high yields from the silyl enol ethers I and II, respectively, by ozonolysis [see, for example, R. D. Clark and C. H. Heathcock, J. Org. Chem., 1976, 41 , 1396] followed by reductive treatment according to known methods [see, for example, L. Aringer and P. Eneroth, Steroids, 1972, 18, 381], and the acyl or glycosyl derivatives thereof are produced in excellent yields from the diols IX and X (R 4 =H) by acylation or glycosylation by methods well established. Also according to the process of the present invention, the known compound of formula XI, friedel-1-en-2-one, is produced in yields higher than 75% by oxidation of the silyl enol ether of general SUBSTITUTE SHEET formula I with 2,3-dichloro-5,6-dicyano-1.4-benzoquinone (DDQ) [see, for example, I. Fleming and I. Paterson, Synthesis, 1979, 736]. The present process for the production of XI illustrates the importance of the silyl enol ethers I and II as intermediates for synthesis and for the selective introduction of α,β-unsaturation in a saturated ketone and is a significant improvement over earlier methods, as described by V. Anjaneyulu and G. S. Rao, Indian J. Chem., 1984, 23B, 663, by oxidation of friedelin V with hydrogen peroxide and selenium dioxide to produce XI in only 2.5% yield , and by B. Talapatra, B. Lahiri, A. Basak, D. K. Pradhan and S. K. Talapatra, Indian J. Chem., 1983, 22B, 741, where XI is obtained in 20% yield starting from 2α-bromofriedel-3-one by reaction with lithium bromide and lithium carbonate. The fungicidal and bactericidal activity of friedelin V, 3-hydroxyfriedel-3-en-2-one VI (R=H), of compounds I, II, III, IV, VII, VIII, IX, X and XI, and the acyl and glycosyl derivatives of VI, VII, VIII, IX, X and XI was demonstrated with bioautographic assay tests with Cladosporium cucumerinum and serology plate assay test with filamentous fungi, yeasts and bacteria, including Streptococcus sp. [for this method, see M. L. Quinta, S. Feio, B. Gigante and M. J. Marcelo Curto, Abstracts II Jornadas Ibericas de Plantas Medicinais, Aromaticas e όleos Essenciais, 1991], showing that in particular the esters of the seco-acids III and IV have higher activity, possessing the structural requirements for the presence of biological activity, namely a rigid polycyclic system with a carboxyl group in the vicinity of an oxygenated function [see, for example, J. Fried, G. W. Krakower, D. Rosenthal and H. Basch, J. Med. Chem., 1965, 8, 279; I. Valterova, J. Klinot and A. Vystrcil, Collect Czech. Chem. Commun., 1983, 48, 649]. SUBSTITUTE SHEET The antifeedant assay tests were carried out by methods well known to those skilled in the art [see, for example, D. H. Miles, A. M. Ly, S. A. Randle, P. A. Hedin and M. L. Burke, J. Agric. Food Chem., 1987, 35, 794; F. N. Lugemwa, F.-Y. Huang, M. D. Bentley, M. J. Mendel and A. R. Alford, J. Agric. Food Chem., 1990, 38, 493] with Leptinitarsa decemlineata, and other insect species of economic significance, such as Epilachna varivestis, Helicoverpa zea and Spodoptera frugiperda. In particular, the antifeedant activity of the new derivatives has advantages over conventional agents used in pest control because they are readily biodegradable and its action is specific, an important requirement for their use in integrated pest control programs to protect agricultural crops of economic importance. Compounds of formulae III, IV, VI, VII, VIII, IX, X and XI, and the acyl and glycosyl derivatives of VI, VII, VIII, IX, X and XI can be used as bioactive agents or formulated in fungicidal, bactericidal, antitumour or antifeedant compositions. The processes of the present invention are illustrated in the following Examples, starting from cork smoker wash solids since it is the most convenient source of friedelin V, and are offered by way of illustration, not by way of limitation. EXAMPLES EXAMPLE 1 This example illustrates the isolation of friedelin V and 3-hydroxyfriedel-3-en-2-one VI (R=H) from cork smoker wash solids and the preparation of 3-acetoxyfriedel-3-en-2-one VI (R=Ac). SUBSTITUTE SHEET Powdered cork smoker wash solids (1.2 kg) were extracted with petroleum ether 40-60°C (3 L) for 2 h in a Soxhiet. The extract was concentrated at reduced pressure and the residue (230 g, 22.9%, w/w), after removal of waxes (4.3%) with petroleum ether, was fracctionated by column chromatography on silica with petrol ether:dichloromethane to yield friedelin V (8% w/w), m.p. 260-4°C, υ max (KBr) 1710 (C=0) cm-1 , 1H-NMR δ 1 ,69 (1H, m , Heq-1), 1 ,95 (2H, m , Hax-1), 2,24 (1 H, q , Hax-4), 2,31 (1H, sex , Hax-2), 2,39 (1H, ddd , Heq-2) ppm; 13C-NMR δ 22,2 (C-1), 41 ,5 (C-2), 213,2 (C-3), 58,2 (C-4), 42,1 (C-5), 41,2 (C-6) ppm; m/z 426 [M] + and 3-hydroxyfriedel-3-en-2-one VI (R=H) (5.4% w/w), m.p. 265-9°C, λ max (EtOH) 275 nm; υ max ( KBr ) 3380 (° H )- 1660 (conjugated 0=0), 1630 (C=C) cm " 1; 1 H-NMR δ (CDCI3) 2,41 (1H, dd, Hax-1), 2,53 ( 1H, dd, Heq-1), 5,96 (1H, ε , OH, exchanges with D 2 0) ppm; 13c-NMR δ (CDCI 3 ) 32, 1 (C-1 ), 194,8 (C-2), 142,2 (C-3), 140,5 (C-4), 39,6 (C-5), 38,1 (C-6) ppm; m/z 440 [M] + . Acetylation of 3-hydroxyfriedel-3-en-2-one VI (R=H) with acetic anhydride and pyridine gave 3-acetoxyfriedel-3-en-2-one VI (R=Ac) (98%), m.p. 308-310°C, υ max (KBr) 1760 (C=0 ester), 1680 (0=0), 1630 (C=C) cm- 1 ; ^ H-NMR δ (CDCI3) 2,24 (3H, s , H 3 CC=0), 2,40 (1H, dd , Hax-1), 2,50 (1H, dd , Heq-1 ); m/z 482 [M] + , 422 [M-HOAcr. SUBSTITUTE SHEET EXAMPLE 2 This example illustrates the preparation of 3-trimethylsiloxy-friedel-2-ene (I, R 1 =Me3) and 3-trimethylsiloxy-friedel-3-ene (II, R 1 =Mβ3). To a mixture of friedelin V (0,53 g) and bis(trimethylsilyl)acetamide (1 ,0 ml) under nitrogen and with stirring, was added hexamethylphosphoramide (1 ,0 ml) and sodium. After ca. 0.5 h, the mixture was diluted with n-pentane and iced water, the organic phase extracted, dried and the solvent removed at reduced pressure to yield 3-trimethylsiloxyfriedel-2-ene (I, R1= Me3) (0.54 g, 87%), m.p. 188-190°C. The structure of this new compound was established by IR, 1 H and 13θNMR and MS: υ max (CHCI3) 1670 (C=C), 1440, 1370, 1090,1050 (SiOC), 900, 840 (SiC) cm " 1 ; 1 H-NMR δ (CDCI3) 0,17 (9H, s , OSi(CH 3 ) 3 ), 1 ,89 (3H, m , 2H-1 , H-4), 4,78 (1H, t, J =1,2, CH=COSi(Me)3) ppm; 13Q-NMR δ (CDCI3) 0,30 ((CH 3 ) 3 Si), 20,8 (C-1), 102,5 (C-2), 151,3 (C-3), 53,0 (C-4), 41,8 (C-6)ppm; m/z498[M] + , 439[M-(Si(Me) 2 +H)] + , 75 [(Me)2Si=OH] + , 73 [(Me) 3 Si] + . The more substituted silyl enol ether, 3-trimethylsiloxy-friedel-3-ene (II, was obtained in a similar way, at 30-50°C and with prolonged reaction times. The structure of this new compound was established by IR, 1 H and 13θNMR and MS: υ max (CHCI3) 2920, 1660, 1595, 890 cm " 1 ; " Η-NMR δ (CDCI3) 0,17 (9H, s, OSi(CH3) 3 ), 0,16 (9H, s , OSi(CH3) 3 ), 4,78 (1H, t , CH=COSiMe 3 ) ppm; m/z 498 [M] + , 439 [M-(Si(Me) 2 +H)] + , 75 [(Me) Si=OH] + , 73 [(Me)3Si] + . SUBSTITUTE SHEET EXAMPLE 3 This example illustrates the preparation of 2o. -hydroxyfriedelan-3-one (cerine, VII, R3=H) 3-Trimethylsiloxy-friedel-2-ene (I, (0.4 g, 0.8 mmol) dissolved in acetone (3 ml) at -5°C was added to a mixture of osmium tetroxide (40,8 mg) in t- butyl alcohol (0.3 ml) and N-methylmorpholine N-oxide (0.114 g) in water and acetone (5 ml, 1 :3). After stirring at 0°C for 3 h, the reaction mixture was kept at room temperature for 8 h. Sodium bisulphite (0.14 g) and Florisil (0.54 g) were added and the suspension stirred for 30 min. After filtration and removal of acetone at reduced pressure, pH was brought to ca. 2, sodium chloride added and the mixture extracted with ethyl acetate, the organic layer dried and concentrated at reduced pressure to give a white solid (0.33 g) which was purified by chromatography on silica to afford 2α-hydroxyfriedelan-3-one (cerine, VII, R3=H), white powder (0.21 g, 59%), m.p. 230°C, υ maχ (CHCl3) 3608 (OH), 1715 (C=0), 1457, 1391 , 1031 (OH) cm-1; 1 H-NMR δ (CDCI3) 1,97 (2H, An , H-1), 2,18 (1H, d, OH-2), 2,82 (1H, q, H-4), 4,08 (1H, q , H-2) ppm; 13c r.m.n. δ (CDCI3) 32,4 (C-1), 76,9 (C-2), 212,0 (C-3), 52,6 (C-4), 42,7 (C-5) ppm; m/z 442 [M] " . SUES! SHEET EXAMPLE 4 This example illustrates the preparation of 2,3-seco-friedelan-2-al-3-oic acid (III, R2=H) and methyl 2,3-seco-friedelan-2-al-3-oate (III, R 2 =CH3). 2α-Hydroxyfriedelan-3-one (cerine, VII, R3=H) (0.7 g) was dissolved in diethyl ether (150 ml) and periodic acid (0.45 g) was added at 0°C, keeping the mixture with stirring for 1 h and then at room temperature for 3 h. Filtration and concentration at reduced pressure gave 2,3-seco-friedelan-2-al-3-oic acid (III, R 2 =H) (0.73 g, 100%). The structure of this new compound was established by IR, 1 H and 13C-NMR and MS of the corresponding methyl ester, methyl 2,3-seco-friedelan-2-al-3-oate (III, R 2 =CH3), m.p. 156-61°C, υ maχ (CHCl3) 2735 (CHO), 1732 (C=0) cm" 1 ; 1H-NMR δ (CDCI3) 2,29 (1H, ddd, Heq-1), 2,30 (1H, q , H-4), 2,45 (1H, ddd , Hax-1 ), 3,62 (3H, s , Cθ2Me), 9,76 (1H, s , CHO) ppm; 13C-NMR δ (CDCI3) 29,7 (C-1), 201,6 (C-2), 175,9 (C-3), 41,3 (C-4), 39,8 (C-5), 51,0 (C-31 , ester) ppm; m/z 472 [M] + , 413 [M-OCOMe] + . EXAMPLE 5 This example illustrates the preparation of friedelane-2α,3β-diol (IX, R 4 =H), 2α,3β-diacetoxyfriedelane (IX, R =Ac) and friedelane-3β,4α-diol (X, R 4 =H). Ozone (30 ml/min) was bubbled for 1 h in a solution of 3-trimethylsiloxy-friedel-2-ene (I, (0-36 g) in dichloromethane and methanol (100 ml, 4:1) at -70°C. Sodium borohydride was added (53 mg) and stirring at room SUBSTITUTE SHEET temperature kept for 12 h. After destruction of excess hydride with 10% hydrochloric acid, the mixture was extracted with dichloromethane, dried and concentrated at reduced pressure to give friedelane-2α,3β-diol (65%) (IX, R 4 =H), m.p. 270-3°C; υ max ( KBr > 3440 (OH) cm-1 ; 1 H-NMR δ (CDCI 3 ) 1 ,58 (2H, m , Heq-1 and H-4), 1,83 (1H, dt, Hax-1), 3,54 (1H, t, Hax-3), 3,99 (1H, q , Heq-2); m/z 444 [M] + , 429 [M-Me] + , 410 [M-2xOH] + . Acetylation of friedelane-2α,3β-diol (IX, R 4 =H) with excess acetic anhydride and pyridine gave quantitatively 2α,3β-diacetoxyfriedelane (IX, R 4 =Ac), m.p. 225-30°C; 1H-NMR δ (CDCI3) 2,06 and 2,08 (6H, s , 2x CH3C=0), 4,79 (1H, t , H-3), 4,70 (1H, t , H-2) ppm; m/z 528 [M] + , 513 [M-Me] + , 468 [M-MeCOOH] + , 453 [M-(MeCOOH+Me)] + . From 3-trimetihylsiloxy-friedel-2-ene (I, under identical conditions was obtained quantitatively friedelane-3β,4α-diol (X, R 4 =H), m.p. 233-7°C; υ maχ (KBr) 3440 (OH) cm-1 ; 1H-NMR δ (CDCI3) 1 ,67 (1H, m , Heq-2), 1 ,98 (1H, m , Hax-2), 3,56 (1H, t , Heq-3) ppm; m/z 444 [M] + , 429 [M-Me] + , 426 [M-H2θ] + , 411 [M-(H2θ+Me)] + . EXAMPLE 6 This example illustrates the preparation of friedel-1-en-3-one (XI). To a solution of 3-trimethylsiloxy-friedel-2-ene (I, (0-17 g) in benzene (10 ml) with stirring was added dropwise a solution of DDQ (90 mg) in benzene (30 SUBSTiTUI t SHE T ml). After stirring at room temperature for 24 h, a saturated solution of sodium bicarbonate (30 ml) was added and the mixture extracted with diethyl ether, the organic layer separated, dried and concentrated at reduced pressure to yield a residue which was purified by chromatography to afford friedel-1-en-3-one XI (0.11 g, 75.9%), white needles m.p. 205-210°C ; λ max (EtOH) 232,4 nm; υ max (KBr) 1660 (C=0 conjugado), 905 (CH=CH) cm"1; 1 H-NMR δ (CDCI3) 2,23 (1H, q , H-4), 2,24 (1H, dd , H-10), 6,05 (1 H, dd , H-1), 6,94 (1 H, dd , H-2) ppm; 13C-NMR δ (CDCI3) 148,6 (C-1), 130,3 (C-2), 201 ,4 (C-3), 57,9 (C-4), 43,8 (C-5), 40,1 (C-6) ppm; m/z 424 [M] + . ci " UTE SHE:

Claims: 1 6- CLAIMS 1. The triterpenoids of general formulae I, II, III and IV ( I I I ) ( IV) wherein R1 represents a dialkyl, trialkyl, triphenyl, diphenylalkyl, alkyldiphenyl, dialkylphenyl, haloalkyi, halophenylalkyi, allylalkyi or alkylaminoalkyl group and R 2 represents a carboxyl group, salt or ester. A process for the preparation of compounds acording to claim 1 , which comprises reaction of friedelin V with a silylating agent in the presence of a bulky strong base, with kinetic or thermodinamic control, to produce regio-specifically the compounds of general formula I or II. SUBSTITUTE SHEET - 1 7- 3. The process according to claim 2, in which the preferred base is hexamethylphosphoramide or lithium isopropylamide. 4. The process according to claims 2 to 3, in which the preferred silylating agent is bis(trimethylsilyl)acetamide or trimethylsilyl chloride. 5. The process according to claim 2, which comprising reaction of compounds of general formula I or II with an oxidising agent to produce respectively the intermediates of general formula VII or VIII, wherein R3 represents H, an acyl or glycosyl group. (VI I ) (VI M ) 6. The process according to claim 5, in which the preferred oxidizing agent is osmium tetroxide in catalytic conditions. 7. The process according to claims 5 and 6, wherein the intermediates of general formula VII or VIII undergo oxidation with a peracid to produce respectively and quantitatively the compounds of general formula III or IV. SUΞST'T'J " SHEET 1 8- 8. The process according to claim 7, in which the preferred peracid is periodic acid. 9. The process according to claim 2, wherein compounds of general formula I or II are subject to ozonolysis followed by reductive treatment to produce in high yields respectively the compounds of general formula IX or X, wherein R 4 represents H, an acyl or glycosyl group. 10. The process according to claim 9, in which the preferred reducing agent is a metal hydride. 11. The process according to claim 2, wherein the intermediate of general formula I is subject to an oxidizing agent to produce friedel-1-en-2-one XI in yields not lower than 75%. SUBSTITUTE SHEET 12. The process according to claim 11 , in which the preferred oxidizing agent is a benzoquinone. 13. A process for prepararing an antifungal composition comprising one compound or a combination of compounds as defined in claims 1 , 5, 7, 9 and 11, and 3-hydroxyfriedel-3-en-2-one VI, including the acyl and glycosyl derivatives thereof. 14. A process for prepararing an antibacterial composition comprising one compound or a combination of compounds as defined in claims 1 , 5, 7, 9 and 11 , and 3-hydroxyfriedel-3-en-2-one VI, including the acyl and glycosyl derivatives thereof. 15. A process for prepararing an antitumour composition suitable for administration to a mammal comprising one compound or a combination of compounds as defined in claims 1 , 5, 7, 9 and 11 , and 3-hydroxyfriedel-3-en-2-one VI, including the acyl and glycosyl derivatives thereof. SUBSTITUTE SHEET 16. A process for prepararing an antifeedant composition comprising one compound or a combination of compounds as defined in claims 1 , 5, 7, 9 and 11 , and 3-hydroxyfriede!-3-en-2-one VI, including the acyl and glycosyl derivatives thereof. 17. Utilization of formulations according to claims 13 to 16, for treating or preventing an infection, wherein an effective amount of a composition prepared by a process according to any of claims 13 to 16 is used. SUBSTITUTE SHEET

Inventors: MARCELO CURTO MARIA JOAO, MOITEIRO CRISTINA MARIA MARTIN, ROSA MARIA REGINA TAVARES, MARCELO CURTO, MARIA, JOAO, MOITEIRO, CRISTINA, MARIA, MARTINS, ROSA, MARIA, REGINA, TAVARES
Applicants: INST NACIONAL DE ENGENHARIA E, MARCELO CURTO MARIA JOAO, MOITEIRO CRISTINA MARIA MARTIN, TAVARES ROSA MARIA REGINA, INSTITUTO NACIONAL DE ENGENHARIA E TECNOLOGIA INDU
Application year: 1993
Main classification: C07J63
IPC codes: C07C62, C07H15, C07J63