Lamectacin, NB-2001
Chemical Name: (6R,7R)-3-[5-Chloro-2-(2,4-dichlorophenoxy)phenoxymethyl]-7-[2-(2-thienyl)acetamido]-3-cephem-4-carboxylic acid
CAS No. 371914-92-0
项目整合开发状态: Preclinical
项目研究机构: NewBiotics (Originator)
合成路线:Acylation of 7-aminocephalosporanic acid (I) with 2-thienyleacetyl chloride (II) in the presence of NaOH led to amide (III).The carboxylate group of (III) was then protected as the corresponding benzhydryl ester (IV) upon treatment with diphenyldiazomethane.Mitsunobu coupling of the hydroxymethyl cephem (IV) with triclosan (V),with partial double-bond isomerization,gave rise to a mixture of the desired delta-3 ether (VI) and its delta-2 isomer (VII),which were separated by repeated column chromatography.Isomerization was minimized by conducting the reaction at -20 C.Finally,removal of the benzhydryl ester group of (VI) was accomplished by treatment with trifluoroacetic acid in the presence of anisole.
📌 参考资料/链接：
参考文献标题:Improved beta-lactam antibiotics
文献作者:Lobl,T.J.; Chan,M.F.; Li,Q.; Doppalapudi,V.R.; Hixon,M.S.; Castillo,R.(NewBiotics,Inc.)
参考来源:WO 0183492
📄 详细内容
合成路线:Acylation of 7-aminocephalosporanic acid (I) with 2-thienyleacetyl chloride (II) in the presence of NaOH led to amide (III).The carboxylate group of (III) was then protected as the corresponding benzhydryl ester (IV) upon treatment with diphenyldiazomethane.Mitsunobu coupling of the hydroxymethyl cephem (IV) with triclosan (V),with partial double-bond isomerization,gave rise to a mixture of the desired delta-3 ether (VI) and its delta-2 isomer (VII),which were separated by repeated column chromatography.Isomerization was minimized by conducting the reaction at -20 C.Finally,removal of the benzhydryl ester group of (VI) was accomplished by treatment with trifluoroacetic acid in the presence of anisole.
参考文献标题:NB2001,a novel antibacterial agent with broad-specrum activity and enhanced potency against beta-lactamase-producing strains
文献作者:Li,Q.; Lee,J.Y.; Castillo,R.; Hixon,M.S.; Pujol,C.; Doppalapudi,V.R.; Shepard,H.M.; Wahl,G.M.; Lobl,T.J.; Chan,M.F.
参考来源:Antimicrob Agents Chemother 2002,46(5),1262