CONVERSION OF 12-ALPHA-HYDROXYANDROSTA-1,4-DIENE-3,17-DIONE INTO A DERIVATIVE OF 12-OXOESTRADIOL - A NOVEL C9-C10 CLEAVAGE REACTION

Reaction of 12 alpha-hydroxyandrosta-1,4-diene-3,17-dione (1) with 2,2 -dimethylpropane-1,3-diol in the presence of pyridinium p-toluenesulfo nate gave the corresponding 17,17-cyclic acetal (2). Oxidation of (2) with chromium trioxide in pyridine gave o[androsta-1,4-diene-17,2'-[1, 3]dioxan]-3,12-dione (5) which underwent base-catalysed cleavage to gi ve the novel 9,10-secosteroid (8). Selective reduction of (1) at C 17 gave 12 alpha,17 beta-dihydroxyandrosta-1,4-dien-3-one (9a); selective protection of this at C 17, followed by oxidation with chromium triox ide in pyridine gave 17 utyldimethylsilyloxy)androsta-1,4-diene-3,12-d ione (10), regioselectively protected as the la,12-ethylenedioxy aceta l (12). Treatment of (12) with lithium in tetrahydrofuran in the prese nce of biphenyl and diphenylmethane effected reductive aromatization o f ring A to give a mixture of 17 oxy)-12,12-ethylenedioxyestra-1,3,5(1 0)-trien-3-ol (15a) and the corresponding 17-alcohol (15b). Conversion of (15a) into the corresponding 3-benzyl ether (14a), followed by aci d-catalysed hydrolysis gave 12-oxoestradiol 3-benzyl ether (13).