Cochrane James R, Exner Claudia J, Jolliffe Katrina A
School of Chemistry, The University of Sydney, Sydney 2006, New South Wales, Australia.
J Org Chem. 2015 May 1;80(9):4491-500. doi: 10.1021/acs.joc.5b00349. Epub 2015 Apr 15.
The structures of the naturally occurring antimicrobial lipodepsipeptides circulocin γ and circulocin δ have been reported to comprise a common cyclic depsipeptide core attached to 3-hydroxy,ω-guanidino fatty acid chains differing in length by two methylene units, but analysis of the reported data suggested that the originally reported structures had incorrect side chain lengths. The total synthesis of both side chain epimers of the originally reported structure of circulocin γ bearing a 19-guanidino-3-hydroxynonadecanoyl (GHND) side chain has been accomplished using a modular approach involving synthesis of the cyclic depsipeptide and side chain fragments followed by a late stage coupling reaction. This revealed that the originally reported structure for circulocin γ bearing the GHND side chain is incorrect and that this structure is actually that of circulocin δ. It has also enabled the absolute configuration of the side chain hydroxy group of the natural product to be assigned as (R). Subsequent synthesis of the analogue bearing a 17-guanidino-3-(R)-hydroxyheptadecanoyl (GHHD) side chain provided confirmation that this revised structure is that of circulocin γ.
据报道，天然存在的抗微生物脂环缩肽circulocinγ和circulocinδ的结构包含一个共同的环状缩肽核心，该核心连接到长度相差两个亚甲基单元的3-羟基，ω-胍基脂肪酸链上，但对报道数据的分析表明，最初报道的结构具有不正确的侧链长度。使用模块化方法完成了最初报道的带有19-胍基-3-羟基十九烷酰基（GHND）侧链的circulocinγ结构的两种侧链差向异构体的全合成，该方法包括环状缩肽和侧链片段的合成，然后进行后期偶联反应。这表明最初报道的带有GHND侧链的circulocinγ结构是不正确的，并且该结构实际上是circulocinδ的结构。它还能够将天然产物侧链羟基的绝对构型指定为（R）。随后合成带有17-胍基-3-（R）-羟基十七烷酰基（GHHD）侧链的类似物，证实了这种修订后的结构是circulocinγ的结构。
