Chemoenzymatic Stereoselective Synthesis of Substituted γ‐ or δ‐lactams with Two Chiral Centers via Transaminase‐catalysed Dynamic Kinetic Resolution,ChemCatChem

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Chemoenzymatic Stereoselective Synthesis of Substituted γ‐ or δ‐lactams with Two Chiral Centers via Transaminase‐catalysed Dynamic Kinetic Resolution
ChemCatChem ( IF 3.8 ) Pub Date : 2020-09-23 , DOI: 10.1002/cctc.202001142
Wenyue Dong ₁ , Peiyuan Yao ₁ , Yingang Wang ₁ , Qiaqing Wu ₁ , Dunming Zhu ₂

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The biocatalytic stereoselective synthesis of lactams with two chiral centers by a dynamic kinetic resolution strategy is demonstrated. Five transaminases were examined for the transamination of chemically synthesized substituted γ‐ or δ‐keto esters. The application of (R)‐ and (S)‐selective enzymes led to the corresponding chiral amines with moderate to high diastereomeric ratios and excellent enantiomeric excess, followed by the formation of γ‐ or δ‐lactams in some cases. Reaction conditions including pH, co‐solvent and ratio of amine donor vs. acceptor were optimised. The stereoselective biotransaminations were performed at semi‐preparative scale, successfully generating the corresponding lactams or amine in 46–70 % isolated yields, up to 99 : 1 diastereomeric ratios and >99 % ee values. This study represents a promising approach to the biocatalytic synthesis of important γ‐ and δ‐lactams with two chiral centers.

中文翻译：

通过转氨酶催化的动态动力学拆分化学酶立体选择合成具有两个手性中心的γ-或δ-内酰胺

通过动态动力学拆分策略证明了具有两个手性中心的内酰胺的生物催化立体选择性合成。检查了五种转氨酶，以化学合成取代的γ-或δ-酮酸酯进行氨基转移。（R）-和（S）-选择酶的应用导致相应的手性胺具有中等至高的非对映异构体比率和出色的对映异构体过量，随后在某些情况下形成了γ-或δ-内酰胺。优化了反应条件，包括pH，助溶剂和胺供体与受体的比例。立体选择性生物转氨反应在半制备规模下进行，成功地以46–70％的分离产率成功生成了相应的内酰胺或胺，非对映异构体比例高达99：1，> 99％ee值。这项研究代表了一种重要的具有两个手性中心的重要γ-和δ-内酰胺生物催化合成方法。

更新日期：2020-09-23

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