The conformation of the side chain in cortisone and related compounds; an infra red and nuclear magnetic resonance study

Abstract

I.r. evidence is presented to indicate that the 17 α,21-disubstituted 20-keto steroids which have been studied contain a weak intramolecular hydrogen bond between the 20-carbonyl group and a 21-hydroxyl substituent in the dominant conformations of the side chain. No hydrogen bond is formed between a 20-carbonyl and a 17 α-hydroxy substituent in the presence of a 21-substituent. The decrease in the geminal coupling constant between the C-21 protons with increasing van der Waals radius of the 21-substituent suggests a preference for this substituent to be approximately eclipsed with the 20-carbonyl, with the keto group lying over ring D. This picture for the preferred conformation of the side chain in cortisone and related compounds is contrary to views previously expressed in the literature.