合成路线:1) The trans-esterification of methyl acetoacetate (I) with allyl alcohol (II) gives the allyl ester (III),which is treated with p-toluenesulfonyl azide (IV) and triethylamine in acetonitrile to yield the diazo derivative (V).The reaction of (V) with tert-butyl-dimethylsilyl triflate (VI) and triethyl amine in dichloromethane affords the enol silyl ether (VII),which is condensed with 3-[1-(tert-butyldimethyl-silyloxy)ethyl-4 acetoxyazetidin-2-one (VIII) by means of ZnCl2 in dichloromethane giving 3-[l-(tertbutyldimethylsilyloxy)ethyl]-4-(4-allyloxy-3-diazo-2,4-dioxobutyl)azetidin-2-one (IX).The cyclization of (IX) by means of rhodium acetate in refluxing benzene yields allyl 6alpha-[l(R)-hydroxyethyl]-2-oxocarbapenam-3-carboxylate (X),which is condensed with 2-(mercaptomethyl)pyridine (XI) by means of diphenyl chlorophosphate and diisopropylamine in acetonitrile affording allyl 6alpha-[l(R)-hydroxy-ethyl]-2-(2-pyridylmethylthio)carbapen-2-em-3-carboxylate (XII).The hydrolysis of (XII) with tetrakis-triphenylphosphine-palladium,triphenylphosphine and potassium 2-ethylhexanoate in dichloromethane gives the potassium salt (XIII),which is finally quaternized with methyl triflate and p-toluenesulfonic acid in acetone.
合成路线:2) The condensation of 4-nitrobenzyl 6-[1(R)-hydroxyethyl]-2-oxocarbapenam-3-carboxylate (XIV) with diphenyl chlorophosphate as before gives 4-nitrobenzyl 6-[1(R)-hydroxyethyl]-2-(2 pyridyl-methylthio)carbapen-2-em-3-carboxylate (XV),which is quaternized with methyl iodide in acetone to afford the quaternized ester (XVI).Finally,this compound is deprotected by hydrogenolysis with H2 over Pd/C in basic THF.
参考文献标题:BMY-25174
文献作者:Prous,J.; Castar,J.
参考来源:Drugs Fut 1988,13(6),511
合成路线:2) The condensation of 4-nitrobenzyl 6-[1(R)-hydroxyethyl]-2-oxocarbapenam-3-carboxylate (XIV) with diphenyl chlorophosphate as before gives 4-nitrobenzyl 6-[1(R)-hydroxyethyl]-2-(2 pyridyl-methylthio)carbapen-2-em-3-carboxylate (XV),which is quaternized with methyl iodide in acetone to afford the quaternized ester (XVI).Finally,this compound is deprotected by hydrogenolysis with H2 over Pd/C in basic THF.
参考文献标题:Synthesis and in vitro activity of C-2 quaternary heterocyclic alkylthio carbapenems
文献作者:Kim,C.U.; Misco,P.F.; Luh,B.Y.; Hitchcock,M.J.M.
参考来源:J Antibiot 1987,40(12),1707
产品链接: CAS No. 91615-54-2››