TY  - JOUR
AU  - Le-Huu, Priska
AU  - Petrović, Dušan
AU  - Strodel, Birgit
AU  - Urlacher, Vlada B.
TI  - One-Pot, Two-Step Hydroxylation of the Macrocyclic Diterpenoid β-Cembrenediol Catalyzed by P450 BM3 Mutants
JO  - ChemCatChem
VL  - 8
IS  - 24
SN  - 1867-3880
CY  - Weinheim
PB  - WILEY-VCH Verlag
M1  - FZJ-2016-06532
SP  - 3755-3761
PY  - 2016
AB  - 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.
LB  - PUB:(DE-HGF)16
UR  - <Go to ISI:>//WOS:000397015100011
DO  - DOI:10.1002/cctc.201600973
UR  - https://juser.fz-juelich.de/record/823900
ER  -