SYNTHESIS OF BIOLOGICAL MARKERS IN FOSSIL-FUELS .7. SELECTED DIASTEREOMERS OF 4-ALPHA-METHYL-5-ALPHA-STIGMASTANE AND 5-ALPHA-DINOSTERANE

Efficient routes for the preparation of selected C-23 and C-24 diaster eomers of the C30 biological markers 4alpha-methyl-5alpha-stigmastane (1) and 5alpha-dinosterane (2) involved the alkylation of 20-(iodometh yl)-4alpha-methyl-5alpha-pregnane with either saturated or alpha,beta- unsaturated esters. The alkylation of 20S)-20-(iodomethyl)-4alpha-meth yl-5alpha-pregnane with methyl (3R)-3-ethyl-4-methylpentanoate furnish ed methyl )-4alpha-methyl-5alpha-stigmastane-23-carboxylate, and a sub sequent decarbomethoxylation provided (20R,24R)-l. The alkylation of 2 0S)-20-(iodomethyl)-4alpha-methyl-5alpha-pregnane with methyl (3S)-3,4 -dimethylpentanoate led to methyl lpha,24-dimethyl-5alpha-cholestane-2 3-carboxylate, and the reduction of this mixture provided principally (20R,23S,24R)-5alpha-dinosteran-29-ol. The further reduction of the me sylate of this isomer secured (20R,23S,24R)-5alpha-dinosterane (2a). T he application of the same sequence of reactions using methyl (3R)-3,4 -dimethylpentanoate led principally to (20R,23R,24S)-5alpha-dinosteran e (2d). The alkylation of 20S)-20-(iodomethyl)-4alpha-methyl-5alpha-pr egnane with methyl (2zeta)-3,4-dimethyl-2-pentanoate and a subsequent reduction of the ester provided a separable mixture of (20R,23R)- and (20R,23S)-5alpha-dinoster-24-(28)-en-29-ol in a 2.4:1 ratio. The conve rsion of (20R,23R)-5alpha-dinoster-24(28)-en-29-ol to the correspondin g tert-butyldimethylsilyl ether, reduction of the DELTA24(28) bond wit h hydrogen over platinum oxide, and deprotection gave principally (20R ,23R,24R)-5alpha-dinosteran-29-ol. The further reduction of this alcoh ol provided (20R,23R,24R)-5alpha-dinosterane (2b). The application of the same sequence of reactions to (20R,23S)-5alpha-dinoster-24(28)-en- 29-ol provided (20R,23S,24S)-5alpha-dinosterane (2c). Diastereoselecti vity at the C-23 position in these ester alkylations was examined as a function of stereochemistry at both the C-20 and C-24 positions.