利用Reformatsky反应合成1-β-碳氢霉烯类抗生素中间体

摘要

以(2R)-3-[(3S,4R)-1-(叔丁基二甲基硅氧基)乙基]-4-乙酰氧基氮杂环丁-2-酮为母体,2-溴乙(丙)酸酯或2-溴丙酰胺为亲核试剂,通过Reformatsky反应合成了一系列新型的1-β碳氢霉烯类抗生素中间体—3-{(2R)-2-[(3S,4R)-1-(叔丁基二甲基硅氧基)乙基]氮杂环丁-2-酮4-基}乙(丙)酸酯(3a～3d)和3-{(2R-2-[(3S,4R)-1-(叔丁基二甲基硅氧基)乙基]氮杂环丁-2-酮-4-基}-N,N-二取代丙酰胺(3e,3i和3k),其结构经1H NMR和13C NMR表征,其中3a～3e和3i未见文献报道.%A series of novel intermediates of 1-β-methyl carbapenem antibiotics, 3-[ (2R)-2-{ (3S, 4R)-4-acetoxy-3-[ (R)-1-(t-butyldimethylsilyloxy) ] ethyl | azetidin-2-one-4-yl] acetic( or propionic) acid esters(3a -3d) and 3-[(2R)-2-{ (3S,4R)4-acetoxy-3-[ (R)-1-( t-butyldimethylsilyloxy ) ] ethyl}azetidin-2-one-4-yl]-N,N-disubstitute-propionic amides(3e, 3i and 3k) , were synthesized by Reformatsky reaction of (3S,4R)-4-acetoxy-3-[ (R)-1-(t-butyldimethylsilyloxy)ethyl]azetidm-2-one with 2-bromacetic acid ester, 2-brompropionic acid ester or 2-brompropionic amide. The structures were characterized by 1H NMR and 13C NMR. 3a ~3e and 3i were new compounds.