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Biocatalytic Enantioselective Hydroaminations for Production of N ‐Cycloalkyl‐Substituted L‐Aspartic Acids Using Two C−N Lyases
Author(s) -
Zhang Jielin,
Fu Haigen,
Tepper Pieter G.,
Poelarends Gerrit J.
Publication year - 2019
Publication title -
advanced synthesis and catalysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.541
H-Index - 155
eISSN - 1615-4169
pISSN - 1615-4150
DOI - 10.1002/adsc.201801569
Subject(s) - chemistry , lyase , enantioselective synthesis , amino acid , edds , stereochemistry , ethylenediamine , combinatorial chemistry , organic chemistry , catalysis , enzyme , biochemistry , phytoremediation , heavy metals , environmental chemistry
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.