Synthesis of 11.beta.,13.beta.- and 13.beta.,16.beta.-propano steroids: probes of hormonal activity

Abstract
Syntheses of 11.beta.,13.beta.- and 13.beta.,16.beta.-propano derivatives of 17.alpha.-ethynyl-17.beta.-hydroxygon-4-en-3-one are described. The 13.beta.,16.beta. bridge was constructed by intramolecular alkylation of the C-16 enolate anion from 3-methoxy-13.beta.-[3''-(tosyloxy)propyl]gona-3,5-dien-17-one, the latter being obtained via Birch reduction of both aryl groups of 17.beta.-hydroxy-3-methoxy-13.beta.-(3''-phenoxypropyl)gona-1,3,5(10),8-tetraene (1). The 11.beta.,13.beta. bridge was constructed by Prins cyclization of 17.beta.-acetoxy-3-methoxy-13.beta.-(3''-oxopropyl)gona-1,3,5(10),9(11)-tetraene, itself obtained via Birch reduction of only the side-chain aryl group of 1. Binding affinities of certain of these compounds and substituted 13.beta.-propyl derivatives of 17.alpha.-ethynyl-17.beta.-hydroxygon-4-en-3-one for the [mouse, rat] uterine cytosol receptor of progesterone are reported, and the origin of the high progestational activity of norgestrel and 11.beta.-substituted progestins is discussed.

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