Enantioselective Synthesis of Chiral Vicinal Amino Alcohols Using Amine Dehydrogenases
Enantioselective Synthesis of Chiral Vicinal Amino Alcohols Using Amine Dehydrogenases
复制标题
使用胺脱氢酶对映选择性合成手性邻氨基醇
DOI：
10.1021/acscatal.9b03889
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发表时间：
2019-12-01
期刊：
影响因子：
12.9
通讯作者：
Turner, Nicholas J.
中科院分区：
文献类型：
--
作者：
Chen, Fei-Fei;Cosgrove, Sebastian C.;Turner, Nicholas J.
手性邻位氨基醇是许多生物活性分子中发现的重要基序。在这项研究中，使用源自梭形赖氨酸芽孢杆菌亮氨酸氨基酸脱氢酶 (AADH) 的工程胺脱氢酶 (AmDH) 研究了 α-羟基酮与氨的生物催化还原胺化。由此鉴定出的 AmDH 能够从相应的 α-羟基酮合成 (S)-构型邻位氨基醇，转化率高达 99%，ee 大于 99%。其中一种 AmDH 变体被用来制备抗结核药物乙胺丁醇的关键中间体。
Chiral vicinal amino alcohols are an important motif found in many biologically active molecules. In this study, biocatalytic reductive amination of alpha-hydroxy ketones with ammonia was investigated using engineered amine dehydrogenases (AmDHs) derived from the leucine amino acid dehydrogenase (AADH) from Lysinibacillus fusiformis. The AmDHs thus identified enabled the synthesis of (S)-configured vicinal amino alcohols from the corresponding alpha-hydroxy ketones in up to 99% conversions and >99% ee. One of the AmDH variants was used to prepare a key intermediate for the antituberculosis pharmaceutical ethambutol.