申请人:THE UNIVERSITY OF NOTRE DAME DU LAC
公开号:EP0306266A1
公开(公告)日:1989-03-08
a-Phosphono-(3p-amino or 3a-alkylazetidin-2-one-1-yl)acetic acids and esters thereof are provided via cyclization process comprising the reaction of a β-hydroxy phosphonomethyl acid amide with triphenylphosphine-di-(C1-C3 alkyl)azodicarboxylate in an anhydrous aprotic solvent. The azetidinones obtained are useful intermediates to carbapenems and carbacephems and monocyclic antibacterials, e.g., a-(dial- kylphosphono)-[[3β-[2-(2-aminothiazol-4-yl)-2-(syn)methoxy- iminoacetylamino]azetidin-2-one-1-yl]]acetic acid and pharmaceutically acceptable salts thereof.
a-膦酰基-(3p-氨基或 3a-烷基氮杂环丁烷-2-酮-1-基)乙酸及其酯类是通过环化工艺提供的,该工艺包括 β-羟基膦酰甲基酸酰胺与二(C1-C3 烷基)偶氮二甲酸三苯基膦在无水无丙烷溶剂中的反应。得到的氮杂环丁酮是碳青霉烯类、碳青霉烯类和单环抗菌药的有用中间体,如 a-(二烷基膦酰基)-[[3β-[2-(2-氨基噻唑-4-基)-2-(异)甲氧基-亚氨基乙酰氨基]氮杂环丁烷-2-酮-1-基]]乙酸及其药学上可接受的盐。