Tetracyclic triterpenes. X. Solvent effect in reactions of tetrasubstituted triterpenoidal olefins with ozone. An allylic oxidation

Abstract

ZDZISLAW PARYZEK and JACEK MARTYNOW. Can. J. Chem. 66, 2130 (1988). The highly hindered 8,9 double bond in lanostane derivatives was found susceptible to oxidation with ozone. The reaction depends on the polarity of the solvent. It is proposed that the structure of the initial complex formed between the olefin and ozone is influenced by the reaction medium. Reaction of 3P-acetoxy-5a-lanost-8-ene with ozone gives 8a,9a-epoxide in methylene chloride, while 3P-acetoxy-5a-lanost-8-en-7-one, an allylic oxidation product, is the main compound formed in ethyl acetate.ZDZISLAW PARYZEK et JACEK MARTYNOW. Can. J. Chem. 66, 2130Chem. 66, (1988. On a trouvC que la double liaison trks empEchke que l'on retrouve dans les positions 8,9 des dCrivCs du lanostane est trks susceptible aux oxydations par l'ozone. La rkaction est influencCe par la polarit6 du solvant. On suggkre que la structure du complexe qui se forme initialement entre 1'olCfine et l'ozone est influencCe par le milieu rkactionnel. Dans le chlorure de mtthylkne, la rkaction de 1'acCtoxy-3P 5a-lanosthe-8 avec l'ozone conduit a l'tpoxyde 8a,9a; par ailleurs, dans 1'acCtate d'tthyle, le produit principal est I'acCtoxy-3P 5a-lanosthe-8 one-7, un produit provenant d'une oxydation allylique.[Traduit par la revue]Retropinacolic rearrangement of a triterpene 3-alcohol, for example 5a-lanostan-3P-01 (I), under the action of phosphorus pentachloride leads to the ring A contracted isopropylidene compound (11). Treatment of the olefin (11) with ozone provides a simple method of preparation of A-nor steroids (111). The sequence shown in eq.[ l ] has been described for pentacyclic (1) 111 and tetracyclic (2) triterpenes, their derivatives possessing a degraded side chain (3), and for 4,4-dimethyl steroids (4). In the lanostane series, 14a-methyl-A-nor-steroids were prepared by this simple degradation route (5).The literature search revealed, however, that ozonolysis of 3-izopropylidene-A-nor-steroids was only rarely performed on substrates possessing an additional olefinic double bond in the molecule. In these cases the reported yields of the degraded compounds were low (15-45%) ( l a , 6).In our approach to 14a-methyl-A-nor-5a-cholest-8-en-3-one (9), the isopropylidene compound 4, which was prepared from 'For Part IX, see ref. 9. 2Author to whom correspondence may be addressed. 3~evision received March 28, 1988. dihydrolanosterol (I), was subjected to oxidative degradation with ozone. The reaction carried out in methylene chloride at -78°C gave the keto-diene 5, which isomerized during work-up to the 5P-isomer 6 (26). Thin-layer chromatographic monitoring of the reaction showed that the epoxy-ketone 7 was the primary product of the reaction. Dehydration of 7 to the diene 5 was catalyzed by an acid4 formed from the solvent under ozonolysis conditions (7). This was evidenced by the isolation of the epoxy-ketone 7 (5 1 % yield) and the enone 9 (5%) from the reaction of 4 carried out in the same solvent containing a small amount of pyridine (8). In the course of the ozonolysi...

Formation of Biologically Active Oxysterols during Ozonolysis of Cholesterol Present in Lung Surfactant

“…The yield of such epoxides during ozonolysis can be dependent on the solvent used and the degree of substitution at the target double bond. For example, lanosterol derivatives have been shown to primarily form epoxides at the very hindered 8,9 double bond during ozonolysis in methylene chloride (37). Al- ternatively, ␤-epoxide could form via lipid peroxidation because it has been proposed that ozone can initiate the formation of radical species (38).…”

Sulphur-mediated five-membered ring expansions. Steroidal examples

“…In the reactions described, the ethylthio substituent was preserved to various extents in the reaction product, when the hydroxydithioacetals (4), (13) The structure of the new compounds described in this work follows from their spectral properties (see Experimental section). Full assignment of the 13C NMR spectra is presented in Table 2.…”

“…C31H540 requires C, 84.1; H, 12.3%). 3 p-( 1,l-Bisethylthioethyl)-3a-hydroxy-14a-methyl-4-nor-5 pcholest-8-ene (13).-The reaction of the ketone (2) (786 mg, 2.05 mmol) under conditions similar to those applied for the synthesis of compound (4) (vide supra), after work-up and chromatography, afforded the 3a-hydroxy derivative (13) (710 mg, 65%), m.p. 71-73 "C (from acetone); v,,, 3 510, 3 430, 1 350, 1 270, 1 085, 1 025, and 985 cm-'; 6 2.72 (2 H, q, J 7 Hz, CH2), 2.69 (2 H, q, J 7 Hz, CH,), 1.61 (3 H, s, 10-Me), 0.72 (3 Synthesis of Compound (13) (LDA Method).-Lithium diisopropylamide was prepared by the dropwise addition of butyl-lithium (7.0 ml, 9.1 mmol) to a rapidly stirred solution of di-isopropylamine (1.28 ml, 9.1 mmol) in tetrahydrofuran (1 5 ml) at 0 "C. The mixture was stirred at 0 "C for 30 min.…”

“…Elution with benzene afforded three pure substances in order of increasing polarity: 3a-ethylthio-3& 14a-dimethyl-5a-cholest-8-en-4-one (1 1) (39 mg, 14%), m.p. 64-64.5 "C (from MeOH-CH2C12); vmax 1 695, 3a-Hydroxy-3P, 14a-dimethyl-5P-cholest-8-en-4-one (1 5)-The a-hydroxy-dithioacetal (13) (280 mg, 0.524 mmol) reacted with (22)(300 mg, 0.95 mmol) in moist toluene in the same manner as described for the reaction of (4) with (22) (oide supra). After 40 min, TLC monitoring indicated complete conversion to a single product.…”

“…The ring-expansion reactions of the hydroxy-dithioacetals (4), (13), and (17) were catalysed by several Lewis acids. The best results were obtained when tetrakis(acetonitrile)copper(I) tetrafluoroborate (22) was used as a thiophile.…”