18-Substituted steroids. Part 7. Synthesis and structure of 11β,18-epoxy-3α,18,21-trihydroxy-5β-pregnan-20-one (3α,5β-tetrahydroaldosterone)

Abstract

3α,5β-Tetrahydroaldosterone (1) has been prepared from 21-deoxy-3α,5β-tetrahydroaldosterone 18-methyl ether 3-(tetrahydropyran-2-yl) ether (6). Kinetically controlled enolisation with lithium di-isopropylamide followed by treatment with chlorotrimethylsilane generated specifically the Δ²⁰⁽²¹⁾-trimethylsilyl enol ether (17), which reacted with 3-chloroperbenzoic acid to give the 18-methyl ether -21-alcohol (18), which was converted into its 21-acetate (27). Acid solvolysis of the protecting groups at C-3 and -18 with anhydrous acetic acid, followed by mild alkaline hydrolysis with sodium hydrogencarbonate afforded 3α,5β-tetrahydroaldosterone (1) in 26% overall yield.