Synthesis and characterization of the 6α- and 6β-hydroxylated derivatives of corticosterone, 11-dehydrocorticosterone, and 11-deoxycortisol

Article abstract of DOI:10.1016/0039-128X(93)90009-C

This report describes the synthesis of 6α,17,21- and 6β,17,21-trihydroxypregn-4-ene-3,20-dione, 6α,7,21- and 6β,11β,21-trihydroxypregn-4-ene-3,20-dione, and - for the first time - that of 6α,21- and 6β,21-dihydroxypregn-4-ene-3,11,20-trione. The former four compounds were prepared by 6-hydroxylation of 17,21-dihydroxypregn-4-ene-3,20-dione and 11β,21-dihydroxypregn-4-ene-3,20-dione, respectively. This was achieved by autoxidation or by oxidation with 3-chloroperbenzoic acid, of the 3-methoxypregna-3,5-dienes of the latter two steroids. The yield of the 6β-hydroxylated steroids, but not of their corresponding 6α-epimers, was higher using autoxidation than the peracid. The two 6-hydroxylated pregnenetriones were prepared from 6α,21-diacetoxy-11β-hydroxypregn-4-ene-3,20-dione and 6β,21-diacetoxy-11β-hydroxypregn-4-ene-3,20-dione, respectively, by oxidation with pyridinium chlorochromate. The above-mentioned six steroids were identified and characterized by nuclear magnetic resonance, infrared, ultraviolet, high performance liquid chromatography, gas chromatography, and mass spectrometry. Keywords: synthesis; corticosteroids; 6-hydroxylation; NMR; HPLC; GC/MS.