Giltrap Andrew M, Haeckl F P Jake, Kurita Kenji L, Linington Roger G, Payne Richard J
School of Chemistry, The University of Sydney, Sydney, NSW, 2006, Australia.
Department of Chemistry, Simon Fraser University, Burnaby, BC, V5A 1S6, Canada.
Chemistry. 2017 Oct 26;23(60):15046-15049. doi: 10.1002/chem.201704277. Epub 2017 Oct 11.
The skyllamycins are a family of highly functionalized non-ribosomal cyclic depsipeptide natural products which contain the extremely rare α-OH-glycine functionality. Herein the first total synthesis of skyllamycins A-C is reported, together with the biofilm inhibitory activity of the natural products. Linear peptide precursors for each natural product were prepared through an efficient solid-phase route incorporating a number of synthetic modified amino acids. A novel macrocyclization step between a C-terminal amide and an N-terminal glyoxylamide moiety served as a key transformation to install the unique α-OH-glycine unit and generate the natural products in the final step of the synthesis.
斯库拉霉素是一类高度官能化的非核糖体环缩肽天然产物，含有极其罕见的α-羟基甘氨酸官能团。本文报道了斯库拉霉素A-C的首次全合成以及这些天然产物的生物膜抑制活性。通过高效的固相路线，结合多种合成修饰氨基酸，制备了每种天然产物的线性肽前体。C端酰胺和N端乙醛酰胺部分之间的新型大环化步骤是关键转化，用于安装独特的α-羟基甘氨酸单元，并在合成的最后一步生成天然产物。
