Enantioselective Synthesis of d‐ and l‐α‐Amino Acids by Enzymatic Transamination Using Glutamine as Smart Amine Donor,Advanced Synthesis & Catalysis

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Enantioselective Synthesis of d‐ and l‐α‐Amino Acids by Enzymatic Transamination Using Glutamine as Smart Amine Donor
Advanced Synthesis & Catalysis ( IF 4.4 ) Pub Date : 2018-12-20 , DOI: 10.1002/adsc.201801278
Egon Heuson ₁ , Franck Charmantray ₁ , Jean-Louis Petit ₂ , Véronique de Berardinis ₂ , Thierry Gefflaut ₁

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Enzymatic transamination is a useful method for the green and highly enantioselective synthesis of chiral amines and non‐canonical amino acids which are of major importance as intermediates in medicinal chemistry. However, transamination reactions are usually reversible and synthetic applications of transaminases often require the implementation of an equilibrium shift strategy. Herein, we report a highly effective approach using glutamine as smart amine donor. This amino acid is converted upon transamination into 2‐oxoglutaramate which undergoes a fast cyclisation displacing the transamination equilibrium. We have developed a new activity assay in order to identify transaminases from biodiversity able to convert various α‐keto acids into valuable amino acids of l‐ or d‐series in the presence of glutamine as amine donor. Discovered transaminases were then used to prepare in high yield and with high enantioselectivity three amino acids of pharmaceutical importance, homophenylalanine, homoalanine and tert‐leucine by simply using a nearly stoichiometric amount of glutamine as amine donor.

中文翻译：

谷氨酰胺作为智能胺供体的酶转氨反应对d-和l-α-氨基酸的对映选择性合成

酶促氨基转移是手性胺和非经典氨基酸绿色和高度对映选择性合成的有用方法，手性胺和非经典氨基酸作为药物化学的中间体非常重要。但是，转氨反应通常是可逆的，转氨酶的合成应用通常需要实施平衡转移策略。在本文中，我们报告了使用谷氨酰胺作为智能胺供体的高效方法。该氨基酸在氨基转移时被转化为2-氧代戊二酸酯，后者经过快速环化作用置换了氨基转移平衡。我们已经开发出一种新的活性测定法，以便从生物多样性中识别出转氨酶，能够将各种α-酮酸转化为l-或d的有价值的氨基酸在存在谷氨酰胺作为胺供体的情况下进行系列分析。然后，通过简单地使用接近化学计量的谷氨酰胺作为胺供体，就可以将发现的转氨酶用于高收率和高对映体选择性的制备具有重要药学意义的三个氨基酸，高苯丙氨酸，高丙氨酸和叔亮氨酸。

更新日期：2018-12-20

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