Efficient Synthesis of a Chiral Precursor for Angiotensin-Converting Enzyme (ACE) Inhibitors in High Space-Time Yield by a New Reductase without External Cofactors

A new reductase, CgKR2, with the ability to reduce ethyl 2-oxo-4-phenylbutyrate (OPBE) to ethyl (R)-2-hydroxy-4-phenylbutyrate ((R)-HPBE), an important chiral precursor for angiotensin-converting enzyme (ACE) inhibitors, was discovered. For the first time, (R)-HPBE with >99% ee was produced via b...

Full description

Saved in:
Bibliographic Details
Published in:Organic letters 2012-04, Vol.14 (8), p.1982-1985
Main Authors: Shen, Nai-Dong, Ni, Yan, Ma, Hong-Min, Wang, Li-Juan, Li, Chun-Xiu, Zheng, Gao-Wei, Zhang, Jie, Xu, Jian-He
Format: Article
Language:English
Subjects:
Angiotensin-Converting Enzyme Inhibitors - chemical synthesis
Angiotensin-Converting Enzyme Inhibitors - chemistry
Angiotensin-Converting Enzyme Inhibitors - metabolism
Candida - enzymology
Escherichia coli - drug effects
Molecular Structure
Oxidoreductases - metabolism
Paracoccus pantotrophus - enzymology
Phenylbutyrates - chemical synthesis
Phenylbutyrates - chemistry
Phenylbutyrates - metabolism
Stereoisomerism
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:A new reductase, CgKR2, with the ability to reduce ethyl 2-oxo-4-phenylbutyrate (OPBE) to ethyl (R)-2-hydroxy-4-phenylbutyrate ((R)-HPBE), an important chiral precursor for angiotensin-converting enzyme (ACE) inhibitors, was discovered. For the first time, (R)-HPBE with >99% ee was produced via bioreduction of OPBE at 1 M without external addition of cofactors. The space-time yield (700 g·L–1·d–1) was 27 times higher than the highest record.
ISSN:1523-7060
1523-7052
DOI:10.1021/ol300397d