%0 Journal Article
%A Le-Huu, Priska
%A Petrović, Dušan
%A Strodel, Birgit
%A Urlacher, Vlada B.
%T One-Pot, Two-Step Hydroxylation of the Macrocyclic Diterpenoid β-Cembrenediol Catalyzed by P450 BM3 Mutants
%J ChemCatChem
%V 8
%N 24
%@ 1867-3880
%C Weinheim
%I WILEY-VCH Verlag
%M FZJ-2016-06532
%P 3755-3761
%D 2016
%X Cytochrome P450 monooxygenases (P450s) are involved in the biosynthesis of a wide range of bioactive secondary metabolites. They often introduce several oxy functionalities at different positions of a substrate through multiple steps and produce a range of oxidized derivatives. Herein, we describe a one-pot two-step hydroxylation of the diterpenoid b-cembrenediol isolated from the plant Nicotiana tabacum. This 14-membered macrocycle shows neuroprotective effects and is, along with its oxidized derivatives, of pharmaceutical interest. Sequential hydroxylations catalyzed by the regioselective P450 BM3 mutants F87A/I263L and V78A/F87G yielded the epimeric (9S,10R/S)-b-cembrenetetraols with a diastereomeric ratio of 48:52. The replacement of the mutant V78A/F87G with L75A/ V78A/F87G in the second step improves the diastereomeric ratio up to 10:90. Absolute configurations of the newly introduced hydroxy groups were determined by quantum-mechanical calculations of NMR spectra.
%F PUB:(DE-HGF)16
%9 Journal Article
%U <Go to ISI:>//WOS:000397015100011
%R 10.1002/cctc.201600973
%U https://juser.fz-juelich.de/record/823900