Testosterone dehydrogenation

This microbiologically selective dehydrogenation of 10/ -chiral A -3-ketones appears to be quite general, and has been applied to 10a-testosterone and a number of di-, tri-, and tetra-cyclic compounds containing both five- and six-membered rings. 

In 1953, after the resurgence of interest in the field. Fried, Thoma, and Klings-berg (F-284) and Vischer and Wettstein (V-1056) discovered the 1-dehydrogenation reaction. The former, usii Cylindrocarpon radicicola with progesterone, testosterone, and Compound S showed that in all instances 1-dehydrotestololactone was... 

We observed dehydrogenation at the 14-position with Wojnowicia g aminis on testosterone (H-381), together with 12o -hydroxylation. It is our view that this is not a true dehydrogenation, but is an artifact arising from prior formation of the 12a , 14a-diol, followed by elimination (not necessarily enzymatic) of the labile 14a-hydroxyl. The driving force for the postulated elimination may come from the 1,3-diaxial interaction of the hydroxyl groups at 12a and 14a. 

In early studies of the potentialities of tritium labeling and % NMR for the solution of biochemical problems, the 1,2-dehydrogenation of testosterone by Cylindrocarpon radicicola was easily and unambiguously shown to proceed by a stereospecific la,23-trans-diaxial elimination (39,48). The substrate fed to the mould comprised 5 parts of [la,2a- H2ltestosterone (XVII) with 1 part of the [13product consisted... 

The inverse procedure, double bond tritiation followed by re-oxidation, allows for the tritium labeling of a,/8-unsaturated carbonyl compounds (Figure 10.7). Applied to the complex steroid 22 it provided [ H]25, in which 95% of the tritium was located at C2. If most tritium in the intermediate 34 had been on the a-face and equally distributed between Cl and C2, in analogy with the preparation of [ C]24 under very similar conditions, then the benzeneselenic anhydride-mediated dehydrogenation must have constituted a net la,2)3 elimination. This selectivity is consistent with the DDQ dehydrogenation of [la,2a- H]androst-4-ene-3,17-dione (36) to give [2- H]androsta-l,4-dien-3,17-dione (2Z) with little tritium at Cl, and DDQ dehydrogenation of [l)3,2)3- H]testosterone 1381 to provide mainly 17)3-hydroxy[l- H]androsta-l,4-dien-3-one (39) . 

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