Conformational analysis of oligomeric flavanoids. Part 1. 4-Arylflavan-3-ols

Abstract

4-(2,4-Dihydroxyphenyl)-5-oxyflavan-3-ols, which incorporate structural features compatible with those of tetrahydropyrano[2,3-h]chromenes, are adopted as models for the conformational demeanour of related phlobatannins. The anomalous behaviour, culminating in atypical Cotton effects (CD) and ³J_HH-coupling constants (¹H NMR) for the C-ring of analogues with a 2,4-cis-arrangement of the phenyl substituents, is attributed to major contributions by A- as opposed to E-conformers for the pyran heterocycle. This is concluded from the persistent geometries generated respectively by three variants of the MM2 force-field for preferred E- and A-conformers, hence allowing calculation of ³J_HH-values for these conformations and consequent estimation of E:A- ratios in conjuction with observed ³J_HH-values. The phenomenon presumably originates from 1,3-allylic strain and concomitant stabilization by π-stacking of the B- and D-rings, and by π-alkyl-interaction between 3-OMe(B) and the π-system of the A-ring.