Biocatalytic Enantioselective Hydroaminations for Production of N‐Cycloalkyl‐Substituted L‐Aspartic Acids Using Two C−N Lyases. Issue 11 (5th March 2019)

• Record Type: Journal Article
• Authors: Zhang, Jielin; Fu, Haigen; Tepper, Pieter G.; Poelarends, Gerrit J.
• Is Part Of: Advanced synthesis & catalysis. Volume 361:Issue 11(2019)
• Page Start: 2433
• Page End: 2437
• Publication Date: 2019-03-05
• Subjects: Biocatalysis -- Hydroamination -- EDDS lyase -- Noncanonical amino acids; Catalysis -- Periodicals; Organic compounds -- Synthesis -- Periodicals; Chemistry -- Periodicals; Chemistry, Technical -- Periodicals; Chemistry -- Periodicals; Catalysis -- Periodicals; Technology, Pharmaceutical -- Periodicals; 547.2
• DOI: 10.1002/adsc.201801569
• Languages: English
• ISSNs: 1615-4150

Abstract

Abstract: N ‐cycloalkyl‐substituted amino acids have wide‐ranging applications in pharma‐ and nutraceutical fields. Here we report the asymmetric synthesis of various N ‐cycloalkyl‐substituted l ‐aspartic acids using ethylenediamine‐ N, N′ ‐disuccinic acid lyase (EDDS lyase) and a previously engineered variant of methylaspartate ammonia lyase (MAL‐Q73A) as biocatalysts. Particularly, EDDS lyase shows broad non‐natural substrate promiscuity and excellent enantioselectivity, allowing the selective addition of homo‐ and heterocycloalkyl amines (comprising four‐, five‐ and six‐membered rings) to fumarate, giving the corresponding N ‐cycloalkyl‐substituted l ‐aspartic acids with >99% e.e. This biocatalytic methodology offers an alternative synthetic choice to prepare difficult N ‐cycloalkyl‐substituted amino acids. Given its very broad amine scope, EDDS lyase is an exceptionally powerful synthetic tool that nicely complements the rapidly expanding toolbox of biocatalysts for asymmetric synthesis of noncanonical amino acids. Abstract :