School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, Georgia 30332, United States.
James Tarpo Jr. and Margaret Tarpo Department of Chemistry, Purdue University, West Lafayette, Indiana 47907, United States.
Org Lett. 2024 Nov 1;26(43):9378-9382. doi: 10.1021/acs.orglett.4c03648. Epub 2024 Oct 21.
The chemical synthesis of -acyl indoles is hindered by the poor nucleophilicity of indolic nitrogen, necessitating the use of strongly basic reaction conditions that encumber elaboration of highly functionalized scaffolds. Herein, we describe the total chemoenzymatic synthesis of the bulbiferamide natural products by the biochemical activity reconstitution of a nonribosomal peptide synthetase assembly line-derived (NRPS-derived) thioesterase that neatly installs the macrocyclizing indolylamide. The enzyme represents a starting point for biocatalytic access to macrocyclic indolylamide peptides and natural products.
-酰基吲哚的化学合成受到吲哚氮亲核性差的阻碍，需要使用强碱反应条件，这给高度官能化支架的构建带来了困难。在此，我们通过非核糖体肽合成酶组装线衍生（NRPS 衍生）硫酯酶的生化活性重建来描述 bulbiferamide 天然产物的全化学酶合成，该酶巧妙地安装了大环化吲哚酰胺。该酶为生物催化获得大环吲哚酰胺肽和天然产物提供了一个起点。
