On the Role of Hydrogen Migrations in the Taxadiene System

Abstract

Taxa-4,11-diene is made by the taxa-4,11-diene synthase (TxS) from Taxus brevifolia. The unique reactivity of the taxane system is characterised by long distance hydrogen migrations in the biosynthesis. This study demonstrates that selective long range hydrogen migrations also play a role in the high energy process of the EI-MS fragmentation of taxa-4,11-diene. A TxS enzyme variant was generated that produces cyclophomactene, a compound that is formed through a concerted process involving a long range proton shift and a ring closure that can also be described as the addition of a methylcarbinyl cation to an olefin. Based on a previous computational study the cyclisation mechanism towards taxa-4,11-diene was suggested to involve two long distance proton migrations instead of one direct transfer. A substrate analog with a shifted double bond was converted with TxS to obtain experimental evidence for this proposal.