Synthesis of 4-d1-testosterone and 4-d1-androstenedione.

Abstract

In order to clarify the stereochemistry at C-4 in enzymatic saturation of Δ4-3-ketoste-roids synthesis of 4-deuterated testosterone and androst-4-ene-3, 17-dione (XVIII, XIX) has been undertaken. The key intermediate leading to the required substrate, 4α-d1-5α-androstane-3β, 4β, 17β-triol 3, 17-bis (dimethyl-tert-butylsilyl) ether (XVI), was prepared by stereospecific reduction with lithium aluminum deuteride from 3β, 17β-dihydroxy-5α-androstan-4-one disilyl ether (XIII), which was readily obtainable from androst-4-ene-3β, 17β-diol disilyl ether (XI) by hydroboration, followed by oxidation with chromium trioxide-pyridine complex. Dehydration of XVI with phosphorus oxychloride in pyridine provided the Δ4 olefine (XVIIb) which on chromium trioxide oxidation was led to the desired compounds. Reductive dehalogenation of 4-bromotestosterone silyl ether (II) with lithium aluminum deuteride and subsequent oxidation with chromium trioxide-pyridine complex afforded 4-d1-testosterone silyl ether (VII) in which the deuterium incorporation, however, proved to be unsatisfactory.