Iminosugars as glycosyltransferase inhibitors: synthesis of polyhydroxypyrrolidines and their evaluation on chitin synthase activity.

Chitin synthase is an enzyme involved in the biosynthesis of chitin, a major structural component of the cell wall of many fungi. Since chitin is absent in vertebrates, chitin synthase has been envisaged as a valuable target in the search for new antifungal agents. In this report, a series of C-2 substituted polyhydroxypyrrolidines were designed and synthesized with the aim of mimicking the glycosylation involved at the transition state of the enzymatic reaction governed by chitin synthase. Some of these models displayed chitin synthase inhibition in the millimolar range. However, no significant antifungal activity was noted on a panel of fungal strains.