Revision of the structure of 3-methoxy-14α-hydroxy-D-homo-1,3,5-(10)-estratrien-17a-one. A simple 1H NMR method for the determination of configuration of hydroxy group in position 5 and/or 14 of the D-homo-steroid skeleton

Abstract

Eignerova and Prochazka found in 1974 the Cotton effect value for 3-methoxy-14α-hydroxy-D-homo-1,3,5(10)-estratrien-17a-one (Ia) to be Δε – 2.76.Calculation of the Δε value for this compound led, however, to a substantially lower value, which suggested the hypothesis that the compound was in fact rather an epimer with the hydroxy group in position 14β. This hypothesis was studied by means of 1H NMR spectra of synthetic models, using the changes of the chemical shifts of angular methyls, induced by in situ acylation of the angular hydroxyl with an α- or β-configuration with trichloroacetyl isocyanate (TAI). The observed TAI-acylation shifts on model compounds indicated the structure Ib with a 14b-configuration of the hydroxyl group. Indenpendent proof has been given by the synthesis of both 14-hydroxy epimers, Ia and Ib. A simple 1H NMR method is proposed for the determination of configuration of the hydroxyl in position 5 or 14 of D-homo-steroid skeleton.