Partial synthesis of compounds related to adrenal cortical hormones; 3alpha, 11 alpha-dihydroxy-17 alpha-steroids.

In Paper II we (1) have shown that methyl 3(a)-acetoxy-11,12epoxycholanate undergoes fission of the epoxide ring with the introduction of the anionic constituent at C-11. The products of such reactions offered, we felt, a possible route to the preparation of 3(a), 11-dihydroxycholanic acid. Marker and Lawson (2) prepared 3((r), 11-dihydroxy-1Zketocholanic acid by bromination and subsequent alkaline hydrolysis of 3(a)-acetoxy12-ketocholanic acid. They could not reduce the product by the Clemmensen method but were able to obtain a crude semicarbazone. They state that Wolff-Kishner reduction was also unsuccessful, although no details of procedure or products were given. Longwell and Wintersteiner (3) reinvestigated the problem and were unable to secure the semicarbazone described by Marker and Lawson. These authors could not obtain either a hydrazone or an oxime and upon treatment of the 3(a), 11-dihydroxy-12ketocholanic acid with sodium ethylate and hydrazine hydrate at 200” both oxygen atoms in Ring C were eliminated. Marker, Shabica, Jones, Crooks, and Wittbecker (4) repeated the reduction of 3((r), ll-dihydroxyIBketocholanic acid, using the method employed by Longwell and Wintersteiner, and obtained a product characterized as 3((u), 11, lBtrihydroxycholanic acid. Although it appeared from these results that the reduction of a 1Bketo bile acid with a hydroxyl group at C-11 would not yield the desired product, there were at least two reasons for investigating this problem. It was possible (1) that the structure of the compound prepared by Marker and Lawson was not that assigned by these authors, or (2) that, if the struct,ure were correct, the epimeric compound with the C-11 hydroxyl group in the opposed configuration would react with ketonic reagents and permit reduction of the carbonyl group. The experiments recorded here were undertaken to explore these possibilities.