Asymmetric synthesis of primary amines catalyzed by thermotolerant fungal reductive aminases.
Asymmetric synthesis of primary amines catalyzed by thermotolerant fungal reductive aminases.
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DOI：
10.1039/d0sc02253e
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发表时间：
2020-05-05
期刊：
影响因子：
8.4
通讯作者：
Turner NJ
中科院分区：
文献类型：
--
作者：
Mangas-Sanchez J;Sharma M;Cosgrove SC;Ramsden JI;Marshall JR;Thorpe TW;Palmer RB;Grogan G;Turner NJ
手性伯胺是合成药物的重要中间体。真菌还原胺酶(RedAms)是一类依赖于NADPH的脱氢酶，它催化一系列酮与等摩尔比的短链伯胺进行还原胺化反应，生成相应的仲胺。在此，我们描述了两个来自Neosartorya spp的红霉素的结构和生化特征以及合成应用。(NfRedAm和NfaRedAm)在真菌RedAm中显示出一种独特的活性，即使用氨作为胺伙伴的卓越能力。使用这些酶，我们展示了一系列伯胺的合成，转化率高达>；97%，并具有出色的对映体过量。温度依赖性研究表明，与该家族中的其他酶相比，这些同系物也具有更高的热稳定性。几种伯胺和仲胺的合成进一步证明了它们的合成适用性，这些伯胺和仲胺的周转数(TN)高达14 000，以及连续的流动反应，在时空中获得了(R)-2-氨基己烷等手性胺，产率高达8.1g L−1 h−1。NfRedAm和NfaRedAm的显著特征突出了它们在合成方面的潜在应用潜力，以及扩大了手性胺合成的生物催化工具箱。真菌还原氨基酶作为制备手性伯胺的有效生物催化剂。
Chiral primary amines are important intermediates in the synthesis of pharmaceutical compounds. Fungal reductive aminases (RedAms) are NADPH-dependent dehydrogenases that catalyse reductive amination of a range of ketones with short-chain primary amines supplied in an equimolar ratio to give corresponding secondary amines. Herein we describe structural and biochemical characterisation as well as synthetic applications of two RedAms from Neosartorya spp. (NfRedAm and NfisRedAm) that display a distinctive activity amongst fungal RedAms, namely a superior ability to use ammonia as the amine partner. Using these enzymes, we demonstrate the synthesis of a broad range of primary amines, with conversions up to >97% and excellent enantiomeric excess. Temperature dependent studies showed that these homologues also possess greater thermal stability compared to other enzymes within this family. Their synthetic applicability is further demonstrated by the production of several primary and secondary amines with turnover numbers (TN) up to 14 000 as well as continous flow reactions, obtaining chiral amines such as (R)-2-aminohexane in space time yields up to 8.1 g L−1 h−1. The remarkable features of NfRedAm and NfisRedAm highlight their potential for wider synthetic application as well as expanding the biocatalytic toolbox available for chiral amine synthesis. Fungal reductive aminases as effective biocatalysts for the preparation of chiral primary amines.
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影响因子：
46.2
作者：
Britton J ;Majumdar S ;Weiss GA
通讯作者：
Weiss GA
影响因子：
4.1
作者：
Rehn, Gustav;Adlercreutz, Patrick;Grey, Carl
通讯作者：
Grey, Carl
影响因子：
5
作者：
Mayol, Ombeline;David, Sylvain;Vergne-Vaxelaire, Carine
通讯作者：
Vergne-Vaxelaire, Carine
影响因子：
9.8
作者：
Constable, David J. C.;Dunn, Peter J.;Zhang, Tony Y.
通讯作者：
Zhang, Tony Y.
影响因子：
3.2
作者：
Mitsukura, Koichi;Suzuki, Mai;Nagasawa, Toru
通讯作者：
Nagasawa, Toru