The stereospecific removal of a C-19 hydrogen atom in oestrogen biosynthesis.
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-3beta,17beta-diol was developed. The 19-(3)H-labelled triol produced by reduction of 19-oxoandrost-5-ene-3beta,17beta-diol with tritiated sodium borohydride is tentatively formulated as 19-hydroxy[(19-R)-19-(3)H]androst-5-ene-3beta,17beta-diol and the 19-(3)H-labelled triol produced by reduction of 19-oxo[19-(3)H]-androst-5-ene-3beta,17beta-diol with sodium borohydride as 19-hydroxy[(19-S)-19-(3)H]-androst-5-ene-3beta,17beta-diol. 3. In the conversion of the (19-R)-19-(3)H-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-(3)H-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.
D000728:Androgens / Q000138:chemical synthesis; D000731:Androstanes / Q000378:metabolism*; D004967:Estrogens / Q000096:biosynthesis*; D004970:Estrone / Q000096:biosynthesis; D005260:Female; D005561:Formates / Q000096:biosynthesis; D006801:Humans; D066298:In Vitro Techniques; D008861:Microsomes / Q000378:metabolism; D010920:Placenta / Q000378:metabolism; D011247:Pregnancy; D014316:Tritium
D000728:Androgens; D000731:Androstanes; D004967:Estrogens; D005561:Formates; D014316:Tritium; D004970:Estrone