This title appears in the Scientific Report :
2016
Please use the identifier:
http://dx.doi.org/10.1002/cctc.201600973 in citations.
One-Pot, Two-Step Hydroxylation of the Macrocyclic Diterpenoid β-Cembrenediol Catalyzed by P450 BM3 Mutants
One-Pot, Two-Step Hydroxylation of the Macrocyclic Diterpenoid β-Cembrenediol Catalyzed by P450 BM3 Mutants
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...
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Personal Name(s): | Le-Huu, Priska |
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Petrović, Dušan / Strodel, Birgit / Urlacher, Vlada B. (Corresponding author) | |
Contributing Institute: |
Strukturbiochemie; ICS-6 |
Published in: | ChemCatChem, 8 (2016) 24, S. 3755-3761 |
Imprint: |
Weinheim
WILEY-VCH Verlag
2016
|
DOI: |
10.1002/cctc.201600973 |
Document Type: |
Journal Article |
Research Program: |
Physical Basis of Diseases |
Publikationsportal JuSER |
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. |