Structure-activity relationships in 16- and 17-substituted 5-androstenes : 3β-Acetoxy-17β-picolyl-5-androsten-16-one

The title compound, 3β-acetoxy-17β-picolyl-5-androsten-16-one, C 27 H 35 NO 3 , was synthesized from a mixture of Z and E isomers of 3β-acetoxy-17-picolinylidene-5-androsten-16-one. The significant difference in these three compounds in the crystalline state lies in the conformation of the five-membered D ring, as well as in the orientation of the bulky substituent at C17. After molecular-mechanics calculations on the individual molecules, the conformational differences of the D ring disappeared, but the differences in the orientation of the substituent at C17 increased. The remarkable differences in biological activity of these compounds could therefore be due to the different orientations of the bulky C17 substituent.