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

Abstract

Deoxy-3a,5P-tetahydroaldosterone (5) has been prepared from 3a-acetoxy-20~-hydroxy-5~-pregnan-l1 -one (7) via the hypoiodite reaction sequence (lead tetra-acetate-iodine-hv; oxidation) followed by reduction and rearrangement of 18,20~-lactone-l1 -ketone (1 3) to the 18,ll ~-lactone-20P-alcohoI ( 14). Reduction of the 18,ll P-lactone-20P-alcohol (1 4) with di-isobutylaluminium hydride afforded the 18,ll p-hemiacetal-2OPalcohol (1 71, which gave the 18,2O-diacetate (1 8). Treatment of the diacetate with acidic methanol gave the 18-methoxy-20(3-acetate (1 9) 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-3a,5P-tetrahydroaldosterone (5) in 20% overall yield.