Lanost-8-en-3-one

The Shaw cyclopalladation reaction (equation 10), reported in 1978, has been developed sufficiently to conclude that it has considerable potenti for functionalization of unactivated methyl groups in die vicinity of a ketone, via the oxime. This was demonstrated with lanost-8-en-3-one, which furnished a cy-clopalladated derivative (32), which allowed functionalization of the 4-Me gro i to CH2D (NaBD4) and CH2I (Ij/CHCls). Attempted oxidation of the cyclohexanone derivative (33) with MCPBA unexpectedly provided the chloromethyl compound (Scheme 29). 

Whereas empirical force-field calculations predict a ring A boat conformation for lanost-8-en-3-one, combined empirical force-field-extended Hiickel molecular orbital calculations favour a ring A chair conformation. Europium-shift n.m.r. results indicate that the molecule adopts the latter conformation. Studies on the peracetic acid-boron trifluoride etherate Baeyer-Villiger oxidation of 4,4-dimethyl-3-keto-triterpenoids to 5-lactones (18) and their subsequent ring contraction to y-lactones have been reported. Dehydrogenation of lanost-8-en-3j8-ol with 2,3-dichloro-5,6-dicyanobenzoquinone afforded, in addition to the corresponding 7,9(1 l)-diene, the aromatic seco-lanostane derivatives (19)... 

Empirical force-field (EFF) calculations failed to predict the A-ring chair conformation of lanost-8-en-3-one, which was indicated by n.m.r. studies. Combined EFF-extended Hiickel MO calculations were successful, however, giving a preference of 1.14 kcal mol over the boat form, although quantitative accuracy is not claimed for the present method of calculation. A treatment of alcohol conformations by molecular mechanics may have applications in predicting the preferred conformations of hydroxy-steroids. 

Lanost-8-en-3-one 9, as well as methyl oleanonate, afforded regioselectively the corresponding [2,3-first synthesis of a new lanostane triterpenoid 11 with a cyano enone moiety in ring A, interesting from the perspective of biological activity, was also achieved <03JOC4991>. 

A related reaction occurs with one of the methyl of the highly congested 2,2, 6,6 -tetramethylcyclohexanone oxime and even with the nonactivated methyl group of steroids, e.g., (E)-lupanone oxime and lanost-8-en-3-one oxime . 

The C-15 epimeric 5a-lanost-8-en-3j3,15-diols have been synthesized.130 Cholesta-5,7-dien-3/3-ol was first converted into 3j3-hydroxy-5a-lanost-7-en-15-one by a previously described route 131 hydride reduction of the 15-ketone yielded a chromatographically separable mixture of 3/3,15a-dihydroxy-5a-lanost-7-ene and its 15j3-epimer. Both 3)3,15-diacetates undergo nuclear double-bond rearrangement in the presence of hydrochloric acid to yield the corresponding A8-3)3,15-diols after hydrolysis. 

An alternative, but rather expensive, method of isolating pure 3/8-acetoxy-5a-lanosta-8,24-dien-3/3-yl acetate from commercial lanosterol has been described. Oxidation of the lanost-8-enes (12) with ruthenium dioxide-sodium periodate gives the 8,9-seco-8,9-diketones (13) together with lesser amounts of the corresponding 8-ene-7,ll-diketones. Under either acidic or basic conditions the former cyclize to afford the C(14a)-homo-B-norlanost-8-en-14a-ones... 

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