Acidic metabolites. VI 20α-isosteroids as intermediates in 20α-dihydrosteroid formation

We have previously shown that human subjects metabolize the 20β-epimer of isocortisol (11β,17,20β-trihydroxy-3-oxo-pregn-4-en-21-a1) to both 20α- and 20β-hydroxy steroid end products. In this paper we describe the synthesis of tritium labeled 20α-epimers of isocortisol and isoTHF (3α,11β,17,20α-tetrahydroxy-5β-pregnan-21-al) and their metabolic fate in humans. Both steroids yielded 20α-hydroxy urinary neutral end-products (cortols and cortolones) and no 20β-hydroxy epimers. Regeneration of 17-ketols from aldols occurred to a small extent with isoTHF, but not with isocortisol. Isocortisol and isoTHF yielded less cortoic acids than did the corresponding ketols. The results provide further evidence that in man the stereochemistry at C-20 of the end-products of corticosteroid metabolism is determined by the configuration of the aldol at C-20 prior to subsequent metabolic events.