Department of Chemistry, University of Waterloo , 200 University Avenue West, Waterloo, Ontario, Canada , N2L 3G1.
Org Lett. 2015 Feb 6;17(3):748-51. doi: 10.1021/acs.orglett.5b00043. Epub 2015 Jan 29.
An entirely solid-phase synthesis of daptomycin, a cyclic lipodepsipeptide antibiotic currently in clinical use, was achieved using a combination of α-azido and Fmoc amino acids. This methodology was applied to the synthesis of several daptomycin analogs, one of which did not contain kynurenine or the synthetically challenging amino acid (2S,3R)-methylglutamate yet exhibited an MIC approaching that of daptomycin.
采用α-叠氮基和 Fmoc 氨基酸的组合，实现了目前临床使用的环状脂肽抗生素达托霉素的全固相合成。该方法应用于几种达托霉素类似物的合成，其中一种不含有色氨酸或合成具有挑战性的氨基酸（2S，3R）-甲基谷氨酸，但表现出接近达托霉素的 MIC。
