Steroids Derived from Bile Acids

Derivatives of bile acids with substituents in Ring C have been described in the preceding papers of this series (l-6). It is the purpose of this paper to assign the probable stereochemical configurations for these compounds. As desoxycholic acid (I)l is a convenient reference compound, it will first be necessary to discuss briefly the spatial arrangement of certain portions of this bile acid. The most probable configuration of desoxycholic acid is 3(0(), 12(a)-dihydroxycholanic acid (7-12). Recent evidence for the configuration assigned to the hydroxyl group at C3 has been furnished by the formation of 3,9-epoxy-A”-cholenic acid (II) from methyl 3(a)-hydroxy-12-bromo-A gJl-cholenate (III) and its reconversion to III on treatment with hydrogen bromide (4). On the basis of these reactions the epoxide bridge of II must lie on the same side of the molecule as the 3-hydroxyl group of III. Construction of models of these compounds with Stuart atoms (13) has shown that an oxygen bridge from Ca to Cg is essentially strain-free when in the a positioq2 that is on the side opposite the angular methyl group at Cl,,, provided that the A-B ring fusion is of the cis-decalin type. No epoxy models can be constructed with a trans A-B ring fusion, or in any case in which the oxygen atom occupies the p configuration. For these reasons the 3,9-epoxy compound appears to be 3(or) ,9(a)-epoxy-A”-cholenic acid (II) .3 Present chemical evidence indicates that the hydrogen at Cg in the bile acids, cortical hormones, and so forth, has the Q: configuration and the B-C ring fusion is trans (7, 15-17). Moreover, x-ray diffraction patterns are in agreement with this conclusion (8, 9, 18). Additional information on this