The Diterpenoid Substrate Analogue 19‐nor‐GGPP Reveals Pronounced Methyl Group Effects in Diterpene Cyclisations

Abstract

AbstractThe substrate analogue 19‐nor‐geranylgeranyl diphosphate (19‐nor‐GGPP) was synthesised and incubated with 20 diterpene synthases, resulting in the formation of diterpenoids in all cases. A total of 23 different compounds were isolated from these enzyme reactions and structurally characterised, if possible including the experimental determination of absolute configurations through a stereoselective deuteration approach. In several cases the missing 19‐Me group in the substrate analogue resulted in opening of completely new reaction paths towards compounds with novel skeletons. DFT calculations were applied to gain a deeper understanding of these observed methyl group effects in diterpene biosynthesis.