Conformational comparison of five follicular fluid meiosis-activating sterol-related active and inactive compounds

The crystal structures of five follicular fluid meiosis-activating sterol-related Δ^8,14-sterol compounds are presented. These are 4,4-di­methyl-23-phenyl-24-nor-5α-chola-8,14-dien-3β-ol, C₃₁H₄₄O, 4,4-di­methyl-22-phenyl-23,24-dinor-5α-chola-8,14-dien-3β-ol, C₃₀H₄₂O, (20R)-4,4-di­methyl-22-oxa-5α,20-chol­es­ta-8,14,24-trien-3β-ol, C₂₈H₄₄O₂, 4,4-di­methyl-23-phenyl-22-oxa-24-nor-5α-chola-8,14-dien-3β-ol–water (4/1), 4C₃₀H₄₂O₂·H₂O, and 4,4-di­methyl-5α-cholesta-8,14-dien-3-one, C₂₉H₄₆O. Two of the derivatives are inactive and three are active as agonists. Preliminary structure–activity relationship studies showed that the positions of the double bonds in the skeleton and the structures of the side chains are important determinants for activity. The conformations of the skeletons were compared with double-bond isomers retrieved from the Cambridge Structural Database Allen & Kennard (1993). Chem. Des. Autom. News, 8 , 1, 31–37]; no significant differences were found. Thus, conformational changes induced by the double bonds are not discriminative with respect to the activity of the compounds. Comparisons of the side-chain conformations of active and inactive structures revealed that the crystal structures were not conclusive as far as correlation of conformation and activity of the side chains were concerned.