SYNTHESIS AND CHARACTERIZATION OF THE 6-ALPHA-HYDROXYLATED AND 6-BETA-HYDROXYLATED DERIVATIVES OF CORTICOSTERONE, 11-DEHYDROCORTICOSTERONE, AND 11-DEOXYCORTISOL

This report describes the synthesis of 6alpha,17,21- and 6beta,17,21-trihydroxypregn-4-ene-3,20-dione, 6alpha,7,21- and 6beta,11beta,21-trihydroxypregn-4-ene-3,20-dione, and-for the first time-that of 6alpha,21- and 6beta,21-dihydroxypregn-4-ene-3,11,20-trione. The former four compounds were prepared by 6-hydroxylation of 17,21-trihydroxypregn-4-ene-3,20-dione and 11beta,21-dihydroxypregn-4-ene-3,20-dione, respectively. This was achieved by autoxidation or by oxidation with 3-chloroperbenzoic acid, of the 3-methoxy-pregna-3,5-dienes of the latter two steroids. The yield of the 6beta-hydroxylated steroids, but not of their corresponding 6alpha-epimers, was higher using autoxidation than the peracid. The two 6-hydroxylated pregnenetriones were prepared from 6alpha,21-diacetoxy-11beta-hydroxypregn-4-ene-3,20-dione and 6beta,21-diacetoxy-11beta-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.