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.