Synthesis of 3α,5α-tetrahydroaldosterone

3α,5α-Tetrahydroaldosterone (12a), a metabolite of aldosterone, has been synthesized from the lactone 2a or, preferably 11β,21-dihydroxy-5-pregnene-3,20-dione-18-oic acid 3,20-di-(ethylene glycol)-ketal (18 → 11) lactone 21-acetate (6b), via 11β,21-dihydroxy-5α-pregnane-3,20-dione-18-oic acid 3,20-di-(ethylene glycol) ketal (18 → 11) lactone 21-acetate (4b). Selective hydrolysis of the latter at C-3 furnished the monoketal 5 which, on reduction with potassium tri-sec-butylborohydride, yielded predominantly 3α,11β,21-trihydroxy-5α-pregnan-20-one-18-oic acid 20-(ethylene glycol)-ketal (18 → 11) lactone (8a) and its acetate 8b. Further reduction with diisobutylaluminum hydride afforded 3α,5α-tetrahydroaldosterone-20-ketal (10a), which was directly hydrolyzed to 12a with dilute acid in tetrahydrofuran-dioxan. Periodate oxidation led to the γ-etiolactone 14a, which was then further converted into 5α-dihydroaldosterone-γ-etiolactone (14c).