Molecular mechanics investigation on side-chain conformations of a 17 alpha-ethyl-17 beta-hydroxy steroid with regard...

Energetically favourable conformations for simultaneous intramolecular rotations of both the 17 alpha ethyl side chain and the 17 beta hydroxyl group of a model steroid are calculated by MM2 molecular mechanics. In accordance with recent IR and NMR interpretations, the 17 alpha substituent is found to preferably adopt conformations which may sterically hinder the formation of hydrogen bonds between the steroidal 17 beta oxygen atom and the receptor protein. Furthermore, the 17 alpha ethyl substitution is computed to influence the D-ring conformation and to alter the location of the 17 beta oxygen function by 28 pm in space.