STEREOCHEMISTRY OF ESTROGEN BIOSYNTHESIS

The stereoselective synthesis of [2β-3H]- and [2α-3H]androst-4-ene-3,17-diones is described. The orientation of the isotope in each followed from the method of preparation and from dehydrogenation with Bacillus sphaericus in which only the 2β-3H was lost. Incubation of each substrate with human placental aroma tase preparation established that the hydrogen loss from C-2 in estrogen biosynthesis is β. The recovered starting material showed a gain in tritium indicating the irreversibility of the loss and raising questions regarding the enolization mechanism proposed for this step. The 1β,2β stereochemistry of aromatization was further confirmed by the tritium analysis of estrone and 2-hydroxyestrone derived from [1,2-3H]testosterone by sequential aromatization and 2 hydroxylation. © 1969, American Chemical Society. All rights reserved.