Biotechnological Development of a Practical Synthesis of Ethyl (S)-2-Ethoxy-3-(p-methoxyphenyl)propanoate (EEHP): Over 100-Fold Productivity Increase from Yeast Whole Cells to Recombinant Isolated Enzymes

被引：56

作者：

Bechtold, Matthias ^{[2
]}

Brenna, Elisabetta ^{[1
]}

Femmer, Christian ^{[2
]}

Gatti, Francesco G. ^{[1
]}

Panke, Sven ^{[2
]}

Parmeggiani, Fabio ^{[1
]}

Sacchetti, Alessandro ^{[1
]}

机构：

[1] Politecn Milan, Dipartimento Chim Mat & Ingn Chim G Natta, I-20131 Milan, Italy

[2] Swiss Fed Inst Technol, Dept Biosyst Sci & Engn D BSSE, CH-4058 Basel, Switzerland

来源：

ORGANIC PROCESS RESEARCH & DEVELOPMENT | 2012年 / 16卷 / 02期

关键词：

OLD YELLOW ENZYME; BAKERS-YEAST; SACCHAROMYCES-CEREVISIAE; COFACTOR REGENERATION; ASYMMETRIC REDUCTION; ENOATE REDUCTASES; ORGANIC-SYNTHESIS; DOUBLE-BOND; SCALE; BIOTRANSFORMATIONS;

D O I：

10.1021/op200085k

中图分类号：

O69 [应用化学];

学科分类号：

081704 ;

摘要：

The coupling of the enantioselective reduction catalyzed by Old Yellow Enzymes (OYEs), together with the in situ substrate feeding product removal (SFPR) concept, significantly improved the productivity of the g-scale preparation of ethyl (S)-2ethoxy-3-(p-methoxyphenyl)propanoate (EEHP), an important precursor of several PPAR-alpha/gamma agonists, such as Tesaglitazar. The OYEs and the glucose dehydrogenase for cofactor regeneration were cloned, overexpressed in Escherichia coli, and purified. The synthetic sequence was completed by a NaClO2 oxidation employing cheap and environmentally friendly conditions. The product was obtained in 94% yield and with an ee of 98% over the two steps.

引用

页码：269 / 276

页数：8

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