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@ARTICLE{LeHuu:823900,
author = {Le-Huu, Priska and Petrović, Dušan and Strodel, Birgit
and Urlacher, Vlada B.},
title = {{O}ne-{P}ot, {T}wo-{S}tep {H}ydroxylation of the
{M}acrocyclic {D}iterpenoid β-{C}embrenediol {C}atalyzed by
{P}450 {BM}3 {M}utants},
journal = {ChemCatChem},
volume = {8},
number = {24},
issn = {1867-3880},
address = {Weinheim},
publisher = {WILEY-VCH Verlag},
reportid = {FZJ-2016-06532},
pages = {3755-3761},
year = {2016},
abstract = {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.},
cin = {ICS-6},
ddc = {540},
cid = {I:(DE-Juel1)ICS-6-20110106},
pnm = {553 - Physical Basis of Diseases (POF3-553)},
pid = {G:(DE-HGF)POF3-553},
typ = {PUB:(DE-HGF)16},
UT = {WOS:000397015100011},
doi = {10.1002/cctc.201600973},
url = {https://juser.fz-juelich.de/record/823900},
}