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The preparation of steroidal heterocycles containing an isoxazole ring fused to the 2,3-positions of the steroid nucleus is described. These were prepared by the reaction of hydroxylamine with either a 2-hydroxymethylene-3-ketosteroid or a 2-acyl-3-ketosteroid. The factors which influence the ratio of androstano [2,3-d] isoxazole to androstano [3,2-c] isoxazole afforded by this reaction are discussed. Several of these novel steroidal heterocycles possess interesting, and often unpredictable, endocrinological activity. The cleavage of steroidal [2,3-d]isoxazoles by means of base leads to the corresponding 2-cyano-3-ketosteroids.In a previous publication2 we outlined attempts to alter the nucleophilic environment near position 3 of the steroid nucleus3 by the attachment of a pyrazóle ring at the 2,3-positions. This approach was based upon the rationalization that the cellular receptor sites would vary sufficiently to make the question of fit one of paramount importance.The success of our initial efforts in synthesizing steroidal [3,2-c [pyrazoles with very high anabolic/ androgenic ratios2 has led us to investigate the very closely related steroidal isoxazoles fused at the 2,3positions.4'5The reaction of hydroxylamine with a 2-hydroxymethylene-3-ketosteroid can conceivably afford both of the two isomeric derivatives,6 the steroidal [2,3-d]isoxazole (I) and the steroidal [3,2-c [isoxazole (II).I can be distinguished readily from II by its facile basecatalyzed conversion to the corresponding 2a-cyano-3ketosteroid. Under the same conditions II is recovered unchanged.7

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