Department of Chemistry, The University of Manchester, Manchester Institute of Biotechnology, 131 Princess Street, Manchester, M1 7DN, UK.
Angew Chem Int Ed Engl. 2022 Jul 25;61(30):e202205054. doi: 10.1002/anie.202205054. Epub 2022 Jun 8.
N-alkanoyl-N-methylglucamides (MEGAs) are non-toxic surfactants widely used as commercial ingredients, but more sustainable syntheses towards these compounds are highly desirable. Here, we present a biocatalytic route towards MEGAs and analogues using a truncated carboxylic acid reductase construct tailored for amide bond formation (CARmm-A). CARmm-A is capable of selective amide bond formation without the competing esterification reaction observed in lipase catalysed reactions. A kinase was implemented to regenerate ATP from polyphosphate and by thorough reaction optimisation using design of experiments, the amine concentration needed for amidation was significantly reduced. The wide substrate scope of CARmm-A was exemplified by the synthesis of 24 commercially relevant amides, including selected examples on a preparative scale. This work establishes acyl-phosphate mediated chemistry as a highly selective strategy for biocatalytic amide bond formation in the presence of multiple competing alcohol functionalities.
N-烷酰基-N-甲基葡糖酰胺（MEGAs）是一种无毒的表面活性剂，广泛用作商业成分，但人们非常希望开发更可持续的合成方法。在这里，我们使用经过精心设计的用于酰胺键形成的截断羧酸还原酶构建体（CARmm-A），提出了一种针对 MEGAs 和类似物的生物催化途径。CARmm-A 能够选择性地形成酰胺键，而不会发生在脂肪酶催化反应中观察到的竞争性酯化反应。通过使用实验设计进行彻底的反应优化，引入了激酶以从多磷酸盐中再生 ATP，从而显著降低了酰胺化所需的胺浓度。通过合成 24 种具有商业相关性的酰胺，包括在制备规模上的选定实例，展示了 CARmm-A 的广泛底物范围。这项工作确立了酰基磷酸介导的化学作为在存在多种竞争醇官能团时进行生物催化酰胺键形成的高度选择性策略。
