Synthesis of Biological Markers in Fossil Fuels. 7. Selected Diastereomers of 4α-Methyl-5α-stigmastane and 5α-Dinosterane

Article abstract of DOI:10.1021/jo00064a039

Efficient routes for the preparation of selected C-23 and C-24 diastereomers of the C30 biological markers 4α-methyl-5α-stigmastane (1) and 5α-dinosterane (2) involved the alkylation of 20-(iodomethyl)-4α-methyl-5α-pregnane with either saturated or α,β-unsaturated esters.The alkylation of (20S)-20-(iodomethyl)-4α-methyl-5α-pregnane with methyl (3R)-3-ethyl-4-methylpentanoate furnished methyl (20R,23ξ,24S)-4α-methyl-5α-stigmastane-23-carboxylate, and a subsequent decarbomethoxylation provided (20R,24R)-1.The alkylation of (20S)-20-(iodomethyl)-4α-methyl-5α-pregnane with methyl (3S)-3,4-dimethylpentanoate led to methyl (20R,23ξ,24R)-4α,24-dimethyl-5α-cholestane-23-carboxylate, and the reduction of this mixture provided principally (20R,23S,24R)-5α-dinosteran-29-ol.The further reduction of the mesylate of this isomer secured (20R,23S,24R)-5α-dinosterane (2a).The application of the same sequence of reactions using methyl (3R)-3,4-dimethylpentanoate led principally to (20R,23R,24S)-5α-dinosterane (2d).The alkylation of (20S)-20-(iodomethyl)-4α-methyl-5α-pregnane with methyl (2ξ)-3,4-dimethyl-2-pentanoate and a subsequent reduction of the ester provided a separable mixture of (20R,23R)- and (20R,23S)-5α-dinoster-24(28)-en-29-ol in a 2.4:1 ratio.The conversion of (20R,23R)-5α-dinoster-24(28)-en-29-ol to the corresponding tert-butyldimethylsilyl ether, reduction of the Δ²⁴⁽²⁸⁾ bond with hydrogen over platinum oxide, and deprotection gave principally (20R,23R,24R)-5α-dinosteran-29-ol.The further reduction of this alcohol provided (20R,23R,24R)-5α-dinosterane (2b).The application of the same sequence of reactions to (20R,23S)-5α-dinoster-24(28)-en-29-ol provided (20R,23S,24S)-5α-dinosterane (2c).Diastereoselectivity 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.