Biocatalytic Enantioselective Hydroaminations for Production of N-Cycloalkyl-Substituted L-Aspartic Acids Using Two C-N Lyases

Jielin Zhang, Haigen Fu, Pieter Tepper, Gerrit Poelarends

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11 Citations (Scopus)
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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.
Original languageEnglish
Pages (from-to)2433-2437
Number of pages5
JournalAdvanced Synthesis & Catalysis
Volume361
Issue number11
DOIs
Publication statusPublished - 6-Jun-2019

Keywords

  • RING-OPENING REACTIONS
  • ASYMMETRIC-SYNTHESIS
  • ASPERGILLOMARASMINE
  • HETEROCYCLES
  • OXETANES

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