Modulation of inherent dynamical tendencies of the bisabolyl cation preorganization in -isozizaene synthase.

The relative importance of preorganization, selective transition state stabilization and inherent reactivity are assessed through quantum chemical and docking calculations for a sesquiterpene synthase (-isozizaene synthase, EIZS). Inherent reactivity of the bisabolyl cation, both static and dynamic, appears to determine the pathway to product, although preorganization and selective binding of the final transition state structure in the multi-step carbocation cascade that forms -isozizaene appear to play important roles.

The viability of nitrone-alkene (3 + 2) cycloadditions in alkaloid biosynthesis.

Although evidence has mounted in recent years for the biosynthetic relevance of [4 + 2] cycloaddition reactions, other cycloadditions have received much less attention. Herein we used density functional theory (DFT) calculations to assess the viability of nitrone-alkene (3 + 2) cycloaddition reactions proposed to occur during the biosynthesis of several alkaloid natural products (flueggines and virosaines). The results of our calculations indicate that these reactions have low enough intrinsic barriers and diastereoselectivity that they can proceed without enzymatic intervention.