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

Efficient Synthesis of a Chiral Precursor for Angiotensin-Converting Enzyme (ACE) Inhibitors in High Space-Time Yield by a New Reductase without External Cofactors
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DOI:
10.1021/ol300397d
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发表时间:
2012-04-20
期刊:
影响因子:
5.2
通讯作者:
Xu, Jian-He
Xu, Jian-He
中科院分区:
化学1区
文献类型:
--
作者:
Shen, Nai-Dong;Ni, Yan;Xu, Jian-He

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发现了一种新的还原酶CgKR2,它能将2-氧代-4-苯基丁酸乙酯(OPBE)还原为血管紧张素转换酶(ACE)抑制剂的重要手性前体(R)-2-羟基-4-苯基丁酸乙酯((R)-HPBE)。首次在没有外加辅因子的情况下,通过OPBE在1M下的生物还原得到了(R)-HPBE,其中>99%ee。时空产量(700g.L-1.d(-1))是最高纪录的27倍。
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.