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Efficient Kilogram-Scale Synthesis of a Novel Oxazolidinone Antibacterial Candidate YG-056SP

文献类型：期刊论文

作者Zhang, Yinyong1,2,3; Yang, Yushe2,3; Meng, Xin2,3; Zhou, Xianli1,4; Guo, Bin2,3
刊名ORGANIC PROCESS RESEARCH & DEVELOPMENT
出版日期2023-01-20
页码12
ISSN号1083-6160
关键词oxazolidinone asymmetric reduction fused ring process development crystal transformation
DOI10.1021/acs.oprd.2c00350
通讯作者Zhou, Xianli(zhouxl@swjtu.edu.cn) ; Guo, Bin(guobin@simm.ac.cn)
英文摘要The development of an improved kilogram-scale synthesis of a novel oxazolidinone antibacterial candidate YG-056SP for the treatment of multidrug-resistant Gram-positive bacterial infection is described. The new process is highlighted by a step economical construction of the chiral N-methyloxazolidone, employing an asymmetric reduction of the carbonyl and methylamine substitution, followed by the cyclization with N,N '-carbonyldiimidazole. Another highlight is the safe construction of the fused ring with high optical purity. Epoxy intermediates were obtained by intramolecular ring closure, and reacted with phenol fragments, followed by reduction, protection, and an intramolecular tandem reaction to afford the fused ring. The endgame process features the completion of the Miyaura reaction and the Suzuki coupling reaction in one pot and tert-butyldimethylsilyl deprotection to make dibenzyl phosphate. Finally, cheap hydrochloric acid was used to deprotect the benzyl group, which delivered YG-056SP with a defined particle-size distribution suitable for preclinical studies after crystal transformation. Compared with the initial synthetic route, the overall yield of this optimized process increased significantly from 2.3 to 29.6%.
WOS关键词RESISTANCE
资助项目National Science and Technology Major Project Key New Drug Creation and Manufacturing Program[2019ZX09721001-001-005]
WOS研究方向Chemistry
语种英语
出版者AMER CHEMICAL SOC
WOS记录号WOS:000924015400001
源URL[http://119.78.100.183/handle/2S10ELR8/303306]  
专题新药研究国家重点实验室
通讯作者Zhou, Xianli; Guo, Bin
作者单位1.Southwest Jiaotong Univ, Sichuan Engn Res Ctr Biomimet Synth Nat Drugs, Sch Life Sci & Engn, Chengdu 610031, Peoples R China
2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
3.Univ Chinese Acad Sci, Sch Pharm, Beijing 100049, Peoples R China
4.Southwest Jiaotong Univ, Affiliated Hosp, Peoples Hosp Chengdu 3, Chengdu 610000, Peoples R China
推荐引用方式
GB/T 7714		 Zhang, Yinyong,Yang, Yushe,Meng, Xin,et al. Efficient Kilogram-Scale Synthesis of a Novel Oxazolidinone Antibacterial Candidate YG-056SP[J]. ORGANIC PROCESS RESEARCH & DEVELOPMENT,2023:12.
APA Zhang, Yinyong,Yang, Yushe,Meng, Xin,Zhou, Xianli,&Guo, Bin.(2023).Efficient Kilogram-Scale Synthesis of a Novel Oxazolidinone Antibacterial Candidate YG-056SP.ORGANIC PROCESS RESEARCH & DEVELOPMENT,12.
MLA Zhang, Yinyong,et al."Efficient Kilogram-Scale Synthesis of a Novel Oxazolidinone Antibacterial Candidate YG-056SP".ORGANIC PROCESS RESEARCH & DEVELOPMENT (2023):12.

入库方式： OAI收割

来源：上海药物研究所

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