Inhibitors of sterol biosynthesis. Carbon-13 nuclear magnetic resonance studies of 9 alpha-fluoro-5 alpha-cholest-8(14)-en-3 beta-ol-15-one and related compounds.

Abstract

The natural abundance 13C nuclear magnetic resonance spectra of a number of 9 alpha-fluoro and 9 alpha-hydroxy-delta 8(14)-15-ketosterols and their derivatives have been studied. Peak assignments for individual carbons of 9 alpha-fluoro-5 alpha-cholest-8(14)-en-3 beta-ol-15-one, 9 alpha-hydroxy-5 alpha-cholest-8(14)-en-3 beta-ol-15-one, 5 alpha-cholest-8(14)-ene-3,15-dione, 9 alpha-fluoro-5 alpha-cholest-8(14)-ene-3,15-dione, 9 alpha-hydroxy-5 alpha-cholest-8(14)-ene-3,15-dione, 3 beta-benzoyloxy-5 alpha-cholest-8(14)-en-3 beta-ol-15-one, 3 beta-benzoyloxy-9 alpha-fluoro-5 alpha-cholest-8(14)-en-15-one, 3 beta-benzoyloxy-5 alpha-cholest-8(14)-en-9 alpha-ol-15-one, 3 beta-acetoxy-9 alpha-fluoro-5 alpha-cholest-8(14)-en-15-one, and 3 beta-acetoxy-5 alpha-cholest-8(14)-en-9 alpha-ol-15-one have been made. Also presented herein are: 1) considerations of the substituent effects of the 9 alpha-hydroxy and 9 alpha-fluoro groups on carbon shieldings, 2) demonstration that the state of oxidation of C-3 in the various delta 8(14)-15-ketosteroids affects the olefinic carbon shieldings due to an apparent long range through space effect of the electric field on the olefinic carbon shieldings, 3) the results of analyses of 13C-19F spin-spin couplings, and 4) the results of considerations of 13C nuclear magnetic resonance studies of the concerned compounds with respect to the conformation of ring B in the various 9 alpha-substituted sterols.