17a-Hydroxy epimers

Also we outlined a serious objection to Wolff s theory, when we considered the 17a-hydroxyandrostane epimers, namely, if Wolff s theory were correct and the hydroxyl group at C-17 were in contact with the receptor surface at the a-face, then surely the 17a-hydroxy epimers are in a much better position to attach themselves to the receptor surface at the a-face and should show considerably higher activity than the 17/8-hydroxy epimers. But this is clearly not the case. 

In the absence of the 11-oxo-group the main product is the 2,3-dioxo-compound. The structure of the major product arising from autoxidation and (EtO)3P reduction of the enol (116) has been confirmed as the 17a-hydroxy-compound (117) by an X-ray analysis, and the minor product of this reaction sequence was thereby shown to be the n-epimer. " ... 

While little or no dehydrocpiandrosterone is excreted in the urine of infants, the excretion of the 17-hydroxy-Aj-Cis steroids is relatively significant, being of the order of 20-880 Mg/24 hours in the first daj s after birth (Nevitz, 1963). Shackicton el al. (1968a) found that the ratio of 17a/ IT/S-hydroxy-As-Cis derivatives is approximately 9 and most of the 17a-androstenediol is excreted in the urine as mono- or disulfate. One explanation for the predominant form of the 17a-epimer is that the 16 -hydroxylasc is selectively active for 17/3-androstenedio , permitting the sul>sequent formation of androatenetriol (Shackleton et al., 1968c). 

The Birch reduction of the A -ketone (370) has enabled 19-nor-D-homotestosterone (376) to be obtained in a single stage [480, 481]. Another variant of this preparation was the preliminary reduction of the 17a-0X0 group of compound (370) with lithium aluminum hydride to give the 17aj8 -hydroxy derivative and the subsequent reduction of the latter by Birches method. In this case, however, the reaction took place non-stereospecifically and as well as (376) its epimer was formed [480]. The Birch reduction of the ketal (372) or its precursor (371) gave 19-nor-D-homoandrostene-3,17a-dione (380) [141]. 

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