HINDERED ROTATION IN ARYLNAPHTHALENE LIGNANS

Many arylnaphthalene lignans show biological activity and although few of them contain stereogenic centers, they may nevertheless be chiral if there is hindered rotation about the aryl-naphthalene bond. A relat ively high barrier to rotation may give rise to separable rotational e nantiomers (atropisomers) which might have quite different pharmacolog ical properties. In order to investigate this possibility we have synt hesized the natural products justicidin A, justicidin B, retro-helioxa nthin, retro-justicidin B, and helioxanthin as well as four other aryl naphthalenes lignan analogs. We have studied the aryl-naphthalene rota tional barrier in these compounds by dynamic NMR and HPLC and find bar riers to rotation ranging from 16.9 to 21.5 kcal/mol. This translates to half-lives for individual atropisomers of less than 10 min at room temperature. The experimentally found barriers are compared to those o btained from molecular orbital calculations.