The Diterpenoid Substrate Analogue 19-nor-GGPP Reveals Pronounced Methyl Group Effects in Diterpene Cyclisations
Kizerbo A Taizoumbe1, Bernd Goldfuss2, Jeroen S Dickschat1
1Kekulé Institute of Organic Chemistry and Biochemistry, University of Bonn, Gerhard-Domagk-Straße 1, 53121, Bonn, Germany.
Abstract:
The 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.
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