Biocatalytic, Stereoselective Deuteration of α-Amino Acids and Methyl Esters

被引：34

作者：

Chun, Stephanie W. ^{[3
,4
]}

Narayan, Alison R. H. ^{[1
,2
]}

机构：

[1] Univ Michigan, Life Sci Inst, Dept Chem, Ann Arbor, MI 48109 USA

[2] Univ Michigan, Program Chem Biol, Ann Arbor, MI 48109 USA

[3] Univ Michigan, Dept Chem, Ann Arbor, MI 48109 USA

[4] Univ Michigan, Life Sci Inst, Ann Arbor, MI 48109 USA

来源：

ACS CATALYSIS | 2020年 / 10卷 / 13期

基金：

美国国家卫生研究院;

关键词：

biocatalysis; alpha-oxoamine synthase; pyridoxal phosphate; deuterium labeling; amino acid; chemoenzymatic synthesis; 8-AMINO-7-OXONONANOATE SYNTHASE; CRYSTAL-STRUCTURE; SERINE PALMITOYLTRANSFERASE; REACTION SPECIFICITY; PHOSPHATE; EXCHANGE; ALANINE; INTERMEDIATE; MECHANISM; ENZYME;

D O I：

10.1021/acscatal.0c01885

中图分类号：

O64 [物理化学（理论化学）、化学物理学];

学科分类号：

070304 ; 081704 ;

摘要：

alpha-H-2 Amino acids are valuable precursors toward labeled pharmaceutical agents and tools for studying biological systems; however, these molecules are costly to purchase and challenging to synthesize in a site- and stereoselective manner. Here, we show that an alpha-oxoamine synthase that evolved for saxitoxin biosynthesis, SxtA AONS, is capable of producing a range of alpha-H-2 amino acids and esters site- and stereoselectively using D2O as the deuterium source. Additionally, we demonstrate the utility of this operationally simple reaction on preparative-scale in the stereoselective chemoenzymatic synthesis of a deuterated analogue of safinamide, a drug used to treat Parkinson's disease.

引用

页码：7413 / 7418

页数：6

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