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The starting point for the synthesis of aldosterone ( I ) was the dihydroxy ketone 11, the preparation of which via the intermediates A -+ B -P C -t D has been described in previous work. The ketone I1 was converted into the furfurylidene derivative I11 which on treatment with methacrylonitrile in methnnolic sodium methoxide was transformed into the adduct IV ( R = H). Acetylation followed by ozonolysis, then saponification, gave on acidification the lactone dicarboxylic acid V ( R = H ) which was transformed by two alternative methods into the diketo lactone VII. Rearrangement with peracid afforded the triacetate VI11 (RL = R 2 = R 3 = Ac) which on mild saponification followed by h'-bromoacetamide oxidation and reacetylation gave the 3-keto diacetate X I 1 (R' = R 2 = H). Bromination and dehydrobromination afforded the unsaturated ketone XI11 which was converted into the ketal XV (R1 = R* = Ac). Saponification gave the diol XV (R' = R 2 = H ) which was transformed by selective reaction with p-toluenesulfonyl chloride in pyridine into the monoester XV (R1 = Ts, R* = H ) . Oxidation with Sarett reagent converted the C-20 hydroxyl to ketone, yielding the substance XVI. This oxidation step eliminated the asymmetry at C-20 which had up to this point resulted in pairs of epimers for each of the substances in the synthetic sequence starting with compound IV. Treatment of the keto ester XVI with potassium t-butoxide effected cyclization to the keto lactol XVII which with 2 moleequivalents of lithium aluminum hydride was selectively reduced to the lactol X I X . Acid hydrolysis afforded the unsaturated ketone X X ( R = H ) which on treatment with methanol and acid was converted into the lactol ether X X ( R = CHa). Oxidation of this substance with Sarett reagent afforded the ketone X X I which was converted by known procedures into the 21-acetoxy compound X X I I ( R = CH,). Hydrolysis of the lactol ether X X I I with 70% acetic acid gave nL-17or-aldosterone-21-acetate (XXIT, R = H ) which was identical with authentic material. Treatment of X X I I with potassium carbonate in aqueous methanol gave the C-17 epimeric mixture from which DL-aldosterone was isolated and compared with authentic material. An alternative approach was also studied and carried to the point of the pentacyclic aldehyde XXXVI. Michael condensation of the furfurylidene ketone I11 with acrylonitrile afforded the adduct X X I I I (R1 = R 2 = H). The diacetate X X I I I (R1 = R 2 = Ac) was converted by treatment with ozone followed by sodium borohydride into the tetrahydroxy compound XXVI. This latter substance was transformed by the action of sodium metaperiodate, followed by treatment of the cleavage product with methanol and acid, into the cyanoacetal XXVII. Treatment with 7070 acetic acid at room temperature selectively hydrolyzed the acetal group to give the cyanoaldehyde X X X which was converted into the diester X X X I I I by the steps: oxidation with chromium trioxide in pyridine to the acid, saponification of the nitrile with potassium hydroxid...

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Epimeric forms of four C-16 halides of estrone methyl ether are reported. Chemical reactions are presented which include proof of structure, isomerization, interconversion and reduction. Two C-17 halides of 16-estrone methyl ether are similarly discussed.Noteworthy and often valuable alterations of clinical activity accompany the exchange of halogen for hydrogen at various points in the steroid nucleus. Progestational, cortical, and androgenicanabolic steroids have received most attention in structure-activity studies.1 Our interest in halogenated estrone derivatives was prompted by the possibility that we could retain the favorable

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