铁载体Hinduchelin的合成

Synthesis of Siderophore Hinduchelin

细菌耐药是我国乃至国际上面临的严峻的公共卫生热点问题,持续危害人们健康和生存。本文根据从印度斯坦链霉菌分离出的铁载体Hinduchelin A的结构特点,经逆合成分析,设计出其全合成路线。2,3-二甲氧基苄胺5与乙酰乙酸乙酯6发生环合反应,然后在碱性条件下(LiOH/MeOH/H_2O)水解成羧酸3,之后再与(R)-2-苯甘氨醇2在多肽缩合剂TBTU作用下形成酰胺,经3步反应得到目标化合物,产率为54.3%。目标化合物的结构经~1H NMR、~(13)C NMR和LC-MS表征,并解析其质谱裂解规律,为进一步的抗菌活性筛选和结构修饰奠定基础。

Antimicrobial resistance is a serious public health concerns in China and even in the world,endangering human health and survival.Based on the structural characteristics of siderophore Hinduchelin A from Streptoalloteichus hindustanus in report,the total synthesis route of this compound was designed via retrosynthesis analysis.2,3-dimethoxybenzylamine 5 underwent a cyclization reaction with ethyl acetoacetate 6 to afford carboxylic acid 3 after hydrolysis reaction under basic conditions(LiOH/MeOH/H2O).The amide 1 was synthesized by treating compound 3 with(S)-2-amino-1-phenylethan-1-ol 2 utilizing the condensing agent TBTU.The target compound was obtained by three steps with a yield of 54.3%.The target compound was characterized by 1H NMR,13C NMR and LC-MS and the fragmentation pathways were analyzed.This study could provide a foundation for further structural modification and antimicrobial activity screening.