Impurity Identification and Scale-Up of a Novel Glycopeptide Antibiotic

doi:10.1021/acs.oprd.1c00064

	Impurity Identification and Scale-Up of a Novel Glycopeptide Antibiotic
	Jiao, Shang 1,2; Guan, Dongliang 3; Xu, Lili 1,2; Liu, Bo 4; Shi, Weiwei 1,2; Li, Jian 1,2; Tang, Feng 1,2; Huang, Wei 1,2,4
刊名	ORGANIC PROCESS RESEARCH & DEVELOPMENT
	2021-11-19
卷号	25 期号:11 页码:2390-2402
关键词	glycopeptide antibiotics impurity analytical method process optimization and development
ISSN号	1083-6160
DOI	10.1021/acs.oprd.1c00064
通讯作者	Tang, Feng(tangfeng2013@simm.ac.cn) ; Huang, Wei(huangwei@simm.ac.cn)
英文摘要	A variety of novel glycopeptide antibiotics have been developed to combat the drug-resistant bacterial strains. Previously, we reported a series of vancomycin derivatives that are modified with lipid tails and extra sugars. SM-V-61, as one of the vancomycin analogues with a trifluoromethyl-biphenyl fragment and galactose, showed enhanced antibacterial activity, improved PK/PD, better water solubility, and safety. However, the deficient synthetic procedure, lower yield, and complicated impurities hindered the further development of the drug candidate SM-V-61. Herein, we reported a further study on SM-V-61 impurity analysis and process optimization. We first synthesized and identified a variety of impurities and established the analytical method for quality analysis and control of SM-V-61. Based on the defined analytical method, we optimized the synthetic procedure for SM-V-61 and operated the synthesis on 30-40 and 500-600 g scales in the laboratory and manufacturing workshop, respectively.
资助项目	National Natural Science Foundation of China (NNSFC)[21877116] ; SIMM Institute Fund[CASIMM0120202009] ; Shanghai Action Plan of Technological Innovation[18431900700] ; National Mega-Project for Innovative Drugs[2019ZX09721001-004-009]
WOS关键词	VANCOMYCIN ; DIMERIZATION ; RETENTION ; PH
WOS研究方向	Chemistry
语种	英语
出版者	AMER CHEMICAL SOC
WOS记录号	WOS:000726748300002
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/299220]
专题	中国科学院上海药物研究所
通讯作者	Tang, Feng; Huang, Wei
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Biotherapeut Discovery Res, CAS Key Lab Receptor Res,CAS Ctr Excellence Mol C, Shanghai 201203, Peoples R China 2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 3.Res Triangle Inst, Ctr Drug Discovery, Res Triangle Pk, NC 27709 USA 4.Univ Chinese Acad Sci, Inst Adv Study, Sch Pharmaceut Sci & Technol, Hangzhou 310024, Peoples R China
推荐引用方式 GB/T 7714	Jiao, Shang,Guan, Dongliang,Xu, Lili,et al. Impurity Identification and Scale-Up of a Novel Glycopeptide Antibiotic[J]. ORGANIC PROCESS RESEARCH & DEVELOPMENT,2021,25(11):2390-2402.
APA	Jiao, Shang.,Guan, Dongliang.,Xu, Lili.,Liu, Bo.,Shi, Weiwei.,...&Huang, Wei.(2021).Impurity Identification and Scale-Up of a Novel Glycopeptide Antibiotic.ORGANIC PROCESS RESEARCH & DEVELOPMENT,25(11),2390-2402.
MLA	Jiao, Shang,et al."Impurity Identification and Scale-Up of a Novel Glycopeptide Antibiotic".ORGANIC PROCESS RESEARCH & DEVELOPMENT 25.11(2021):2390-2402.