期刊
CATALYSIS SCIENCE & TECHNOLOGY
卷 4, 期 10, 页码 3657-3664出版社
ROYAL SOC CHEMISTRY
DOI: 10.1039/c4cy00642a
关键词
-
资金
- Austrian Science Fund (FWF project) [P20903-N17, P22115-N17]
- European Commission [289646]
- COST Action CM1303 SysBioCat
- NAWI Graz
- OeFG
- Austrian BMWFJ
- BMVIT
- SFG
- Standortagentur Tirol
- ZIT through the Austrian FFG-COMET-Funding Program
- Royal Society Wolfson Research Merit Award
Chemo-enzymatic deracemisation was applied to obtain the (S)-enantiomer of 1-benzylisoquinolines from the racemate in high isolated yield (up to 85%) and excellent optical purity (ee > 97%). The one-pot deracemisation protocol encompassed enantioselective oxidation by a monoamine oxidase (MAO-N) and concomitant reduction of the resulting iminium species by ammonia-borane. The challenge was the oxidation at the sterically demanding chiral centre. Recently developed variants of MAO-N, featuring an enlarged active-site pocket, turned out to be suitable biocatalysts for these substrates. In contrast to previous MAO-N variants, which preferentially converted the (S)-enantiomer, the MAO-N variant D11 used in the present study was found to oxidise all tested benzylisoquinoline substrates with (R)-enantiopreference. The structural determinants of enantioselectivity were investigated by means of protein-ligand docking simulations. The applicability of the deracemisation system was demonstrated on preparative scale (150 mg) for three benzylisoquinoline alkaloids (natural as well as non-natural), including the hypotensive and antispasmodic agent (S)-reticuline.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据