18-Substituted steroids. Part 6. Synthesis of 3α,18-dihydroxy-11β,18-epoxy-5β-pregnan-20-one (21-deoxy-3α,5β-tetrahydroaldosterone)

Abstract

21-Deoxy-3α,5β-tetahydroaldosterone (5) has been prepared from 3α-acetoxy-20β-hydroxy-5β-pregnan-11-one (7)via the hypoiodite reaction sequence (lead tetra-acetate–iodine–hv; oxidation) followed by reduction and rearrangement of 18,20β-lactone-11-ketone (13) to the 18,11β-lactone-20β-alcohol (14). Reduction of the 18,11β-lactone-20β-alcohol (14) with di-isobutylaluminium hydride afforded the 18,11β-hemiacetal-20β- alcohol (17), which gave the 18,20-diacetate (18). Treatment of the diacetate with acidic methanol gave the 18-methoxy-20β-acetate (19) by selective solvolysis at C-18. Removal of the 20-acetate with lithium aluminium hydride, followed by oxidation with Collins' reagent, and acid hydrolysis of the protecting groups then afforded 21-deoxy-3α,5β-tetrahydroaldosterone (5) in 20% overall yield.