应用化学2017，Vol.34Issue(7)：768-773,6.DOI:10.11944/j.issn.1000-0518.2017.07.160389
阿莫西林杂质L的化学合成
Synthesis of Amoxicillin Inpurity L
摘要
Abstract
Amoxicillin is a β-lactam antibiotic used for the treatment of a number of bacterial infections.It is on the World Health Organization′s List of Essential Medicines, and one of the most important medications needed in a basic health system.The insufficient sources of its impurity L, i.e., (2S,5R,6R)-6-((2S,5R,6R)-6-((R)-2-amino-2-(4-hydroxyphenyl)acetamido)-3,3-dime-thyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxamido)-3,3-dimethyl-7-oxo-4-thia-1-azabicy-clo[3.2.0]heptane-2-carboxylic acid(6-APA amoxicilin amide), affect the quality control of the product.Herein, the first synthesis of amoxicillin impurity L, was reported by using a simple and efficient method.The starting materials of 6-aminopenicilanic acid and amoxycillin trihydrate were converted to intermediate compounds 3 and 6 through three-step and one-step reactions, respectively.By using benzotriazole-1-yl-oxytripyrrolidinophosphonium hexafluorophosphate(PyBOP) as peptide coupling reagent, we successfully synthesized key intermediate 7 from compounds 3 and 6 in 76% yield, which was subsequently transformed to 6-APA amoxicillin amide by fully deprotection of benzyl and two carbobenzyloxy(Cbz) protecting groups.This method not only increases the source of the standard substance for quality control of amoxicillin, but also provides inspiration for novel β-lactam antibiotic and antiallergic research.关键词
β-内酰胺/阿莫西林杂质L/酰胺缩合试剂Key words
β-lactam/amoxicillin impurity L/peptide coupling reagent分类
化学化工引用本文复制引用
姚飞飞,崔巍,肖德海,张吉凤..阿莫西林杂质L的化学合成[J].应用化学,2017,34(7):768-773,6.基金项目
国家自然科学基金(21402182),吉林省与中国科学院科技合作高技术产业化专项资金项目(2017SYHZ0014)资助 （21402182）
Supported by the National Natural Science Foundation of China(No.21402182), Jilin Province and Chinese Academy of Sciences Cooperated High-tech Industrialization Special Fund Project(No.2017SYHZ0014) （No.21402182）
