Integrated Biocatalysis in Multistep Drug Synthesis without Intermediate Isolation: A de Novo Approach toward a Rosuvastatin Key Building Block

被引：22

作者：

Metzner, Richard ^{[1
]}

Hummel, Werner ^{[2
]}

Wetterich, Frank ^{[3
]}

Koenig, Burghard ^{[4
]}

Groeger, Harald ^{[1
]}

机构：

[1] Univ Bielefeld, Fac Chem, D-33615 Bielefeld, Germany

[2] Univ Dusseldorf, Julich Res Ctr, Inst Mol Enzyme Technol, D-52426 Julich, Germany

[3] Sandoz Int GmbH, D-83607 Holzkirchen, Germany

[4] Sandoz Ind Prod GmbH, D-65929 Frankfurt, Germany

来源：

ORGANIC PROCESS RESEARCH & DEVELOPMENT | 2015年 / 19卷 / 06期

关键词：

BETA-HYDROXYKETONES; PYRIMIDINE; REDUCTION;

D O I：

10.1021/acs.oprd.5b00057

中图分类号：

O69 [应用化学];

学科分类号：

081704 ;

摘要：

In this contribution, we report the chemoenzymatic preparation of a key building block for the active pharmaceutical ingredient rosuvastatin, one of the "top 5 blockbuster drugs" with a worldwide market value of 6.25 billion USD in 2012, via a seven-step synthesis without isolation of intermediates and with incorporation of two highly efficient biotransformations. This chemoenzymatic process reaches excellent space-time yields by using high substrate concentrations (several hundred grams per liter), emphasizing the potential of biocatalysis for industrial processes related to pharmaceutical drug synthesis and the compatibility of enzyme chemistry with classical organic synthesis.

引用

页码：635 / 638

页数：4

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