A novel synthetic approach to (20R)- and (20S)-21-hydroxy steroids. Synthesis of a marine sterol 21-hydroxycholesterol

A short and efficient synthesis of steroid synthons, di(tert-butyldimethylsilyl) ethers of 3,21-dihydroxy-24-nor-chol-5-en-23-al (8 and 10) and of ethyl 3,21-dihydroxy-25-homo-chola-5,23-dien-25-oate (9 and 11), having natural (20R) and unnatural (20S) configuration from 3β-(tert-butyldimethylsilyloxy)-14α,20ξ-card-5-enolide (2) is reported. Further elongation of the side chain of these synthons provides a new method for the synthesis of (20R) and (20S)-21-hydroxy steroids. The utility of the method was exemplified by the synthesis of a natural marine sterol – 21-hydroxycholesterol (18).

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► Synthetic cardenolide is a substrate for the synthesis of 21-hydroxy steroids.
► Steroid synthons having (20R)- and (20S)-configuration were obtained.
► Side chain elongation was achieved by Wittig-type reaction of 23-aldehydes.
► Aminolysis of the cardenolide gave 24-norchol-5-en-23-oic acid amides.