18-Substituted steroids. Part 5. Further studies on the synthesis of 11β,18,21-trihydroxypregn-4-ene-3,20-dione (‘18-hydroxycorticoster-one’)

Abstract

18-Hydroxycorticosterone’(1) has been prepared from 3β,11α-diacetoxypregn-5-en-20-ol (7) by application of the ‘hypoiodite’ reaction sequence [Pb(OAc)₄–I₂–hv; oxidation; solvolysis] to obtain the 18-hydroxy-20-one (in the hemicetal form; 8). Hydrolysis followed by oxidation at C-3 and C-11 gave 18-hydroxypregn-4-ene-3,11,20-trione 18,20-hemiacetal (3), which was then doubly protected as its 20-methoxy 3-semicarbazone derivative (4) to allow reduction of the 11-oxo group to the 11β-alcohol. Brief reaction of the product with lead tetra-acetate–acetic acid then gave ‘18-hydroxycorticosterone’ 21-acetate in a single step. The readily available 3β,11α-diacetoxypregn-5-eno-18,20-lactone (10) was also investigated as a possible precursor of 18-hydroxycorticosterone, but with disappointing results.