The stereospecific removal of a C-19 hydrogen atom in oestrogen biosynthesis

Abstract

1. The synthesis of a number of 19-substituted androgens is described. 2. A method for the partially stereospecific introduction of a tritium label at C-19 in 19-hydroxyandrost-5-ene-3β,17β-diol was developed. The 19−3H-labelled triol produced by reduction of 19-oxoandrost-5-ene-3β,17β-diol with tritiated sodium borohydride is tentatively formulated as 19-hydroxy[(19-R)-19−3H]androst-5-ene-3β,17β-diol and the 19−3H-labelled triol produced by reduction of 19-oxo[19−3H]-androst-5-ene-3β,17β-diol with sodium borohydride as 19-hydroxy[(19-S)-19−3H]-androst-5-ene-3β,17β-diol. 3. In the conversion of the (19-R)-19−3H-labelled compound into oestrogen by a microsomal preparation from human term placenta more radioactivity was liberated in formic acid (61·6%) than in water (38·4%). In a parallel experiment with the (19-S)-19−3H-labelled compound the order of radioactivity was reversed: formic acid (23·4%), water (76·2%). 4. These observations are interpreted in terms of the removal of the 19-S-hydrogen atom in the conversion of a 19-hydroxy androgen into a 19-oxo androgen during oestrogen biosynthesis. 5. It is suggested that the removal of C-19 in oestrogen biosynthesis occurs compulsorily at the oxidation state of a 19-aldehyde with the liberation of formic acid.