Metal-chelating aminocarboxylic acids are being used in a broad range of domestic products and industrial applications. With the recent identification of the fungal natural product aspergillomarasmine A as a potent and selective inhibitor of metallo-β-lactamases and a promising co-drug candidate to fight antibiotic-resistant bacteria, the academic and industrial interest in metal-chelating chiral aminocarboxylic acids further increased. Here, we report a biocatalytic route for the asymmetric synthesis of aspergillomarasmine A and various related aminocarboxylic acids from retrosynthetically designed substrates. This synthetic route highlights a highly regio- and stereoselective carbon–nitrogen bond-forming step catalysed by ethylenediamine-N,N′-disuccinic acid lyase. The enzyme shows broad substrate promiscuity, accepting a wide variety of amino acids with terminal amino groups for selective addition to fumarate. We also report a two-step chemoenzymatic cascade route for the rapid diversification of enzymatically prepared aminocarboxylic acids by N-alkylation in one pot. This biocatalytic methodology offers a useful alternative route to difficult aminocarboxylic acid products.

金属螯合氨基羧酸已被广泛用于家庭产品和工业应用中。随着最近鉴定出真菌天然产物曲霉氨基茉莉A作为金属β-内酰胺酶的有效和选择性抑制剂以及对抗抗生素抗性细菌的有前途的候选药物，金属螯合手性氨基羧酸的学术和工业兴趣进一步提高。增加。在这里，我们报告了从逆向合成设计的底物不对称合成曲霉罗拉明A和各种相关的氨基羧酸的生物催化途径。该合成路线强调了乙二胺-N，N催化的高度区域和立体选择性的碳-氮键形成步骤′-二琥珀酸裂合酶。该酶显示出广泛的底物混杂性，接受多种具有末端氨基的氨基酸以选择性地添加至富马酸酯。我们还报告了两步化学酶联级联途径，用于通过一锅中的N-烷基化快速制备酶法制备的氨基羧酸。这种生物催化方法为困难的氨基羧酸产物提供了有用的替代途径。