1,2- or 1,3-Hydride Shifts: What Controls Guaiane Biosynthesis?

Abstract

A systematic computational study addressing the entire chemical space of guaianes in conjunction with an analysis of all known compounds shows that 1,3-hydride shifts are rare events in guaiane biosynthesis. As demonstrated here, 1,3-hydride shifts towards guaianes can only be realized for two stereochemically well defined out of numerous possible stereoisomeric skeletons. One example is given by the mechanism of guaia-4(15)-en-11-ol synthase from California poplar, an enzyme that yields guaianes with unusual stereochemical properties. The general results from DFT calculations were experimentally verified through isotopic-labeling experiments with guaia-4(15)-en-11-ol synthase.