Remarkable differences in the reactivity of echinadiol and shiromodiol, biologically active epimeric germacrane derivatives

Abstract

Treatment of echinadiol with a variety of acids gave a 8,9-secoguaiane aldol resulting from the cyclofragmentation of the ten-membered ring. Under these conditions its C-8 epimer (shiromodiol) did not react or underwent esterification of the hydroxy group at C-8. Allylic oxidation of both epimers occurred with oxidation of the allylic methyl to the formyl level and retention of configuration of the endocyclic trans(Z) double bond. However, whereas the enal from shiromodiol was stable, that from echinadiol smoothly underwent Z–E isomerization. Low-temperature NMR experiments showed that echinadiol and shiromodiol exist in solution as a mixture of parallel and crossed rotamers, whose ratio is ca. 1 : 5 for shiromodiol and 4 : 1 for echinadiol. Anchimeric stabilization of an incipient positive charge at C-10 or C-14 by the C-8 β-hydroxy group of echinadiol might be responsible for the observed differences in reactivity.