A stereoselective synthesis of 7α-(3'-carboxypropyl)estradiol from a noncontrolled substance

Article abstract of DOI:10.1016/S0039-128X(97)00088-3

Alkylation of 3.17β-bis(2-trimethylsilyl)ethoxymethyl-1,3,5(10) estratriene-6-one (2) with 5-bromo-1-pentene using NaHMDS in THF afforded 3,17β-bis(2-trimethylsilyl)ethoxymethyl-7-α-(4'-pentenyl)- 1,3,5(10)estratriene-6-one (3) in excellent stereoselectivity (>95% epimeric excess). Functionalization of the side chain in compound 3 was accomplished via ozonolysis, oxidation and esterification to give 5 in 72% yield. The reduction of ester (5) using NaBH₄ in MeOH afforded the corresponding 6α- hydroxy compound (6) as a single isomer in 72% yield. The hydroxyl group in 6 was removed by converting to the corresponding xanthate (7) followed by reduction rising n-Bu₃SnH to afford 8 in good yield. Finally, the SEM protective groups in 8 were removed, after which the ester function was hydrolyzed with LiOH to give 7α-(3'-carboxypropyl)estradiol (10), in 10.6% overall yield from 3.