合成路线:The esterification of penicillanic acid (I) with chloromethyl chlorosulfate by means of KHCO3 and tetrabutylammonium hydrogen sulfate in CH2Cl2 - water gives chloromethyl penicillanate (II),which is oxidized to chloromethyl penicillanate 1,1-dioxide (III) by means of H2O2 and sodium tungstate in isopropanol.The reaction of (III) with Na in acetone affords iodomethyl penicillanate 1,1-dioxide (IV),which is condensed with potassium 6-[N-(1-methoxycarbonylpropen-2-yl)-D-alpha-amino-alpha-phenylacetamido]penicillanate (V) in DMF yielding 1,1-dioxopenicillanoyloxymethyl-6-[N-1-methoxycarbonylpropen-2-yl)-D-alpha-amino-alpha-phenylacetamido penicillanate (VI).Finally,this compound is deprotected by treatment with 4N HCl.Compound (III) can also be obtained by direct esterification of penicillanic acid 1,1-dioxide (VII) with chloromethyl chlorosulfate as before.Compound (V) is obtained bv reaction of ampicillin (VIII) with methyl acetoacetate (IX) by means of K2CO3 in DMF.
参考文献标题:VD-1825 and VD-1827
文献作者:Castar,J.; Serradell,M.N.; Sweetman,A.J.; Blancafort,P.
参考来源:Drugs Fut 1981,6(8),496
合成路线:The condensation of 6-[2-(benzyloxycarbonylamino)-2-phenylacetamido]penicillanic acid potassium salt (I) with chloromethyl penicillanate 1,1-dioxide (II) by means of NaI in DMSO gives the target bisester.
参考文献标题:Bis-esters of methanediol with penicillins and penicillanic acid 1,1-dioxide
文献作者:Bigham,E.C.(Pfizer Inc.)
参考来源:US 4244951
合成路线:The esterification of penicillanic acid (I) with chloromethyl chlorosulfate by means of KHCO3 and tetrabutylammonium hydrogen sulfate in CH2Cl2 - water gives chloromethyl penicillanate (II),which is oxidized to chloromethyl penicillanate 1,1-dioxide (III) by means of H2O2 and sodium tungstate in isopropanol.The reaction of (III) with Na in acetone affords iodomethyl penicillanate 1,1-dioxide (IV),which is condensed with potassium 6-[N-(1-methoxycarbonylpropen-2-yl)-D-alpha-amino-alpha-phenylacetamido]penicillanate (V) in DMF yielding 1,1-dioxopenicillanoyloxymethyl-6-[N-1-methoxycarbonylpropen-2-yl)-D-alpha-amino-alpha-phenylacetamido penicillanate (VI).Finally,this compound is deprotected by treatment with 4N HCl.Compound (III) can also be obtained by direct esterification of penicillanic acid 1,1-dioxide (VII) with chloromethyl chlorosulfate as before.Compound (V) is obtained bv reaction of ampicillin (VIII) with methyl acetoacetate (IX) by means of K2CO3 in DMF.
参考文献标题:Mutual pro-drugs of beta-lactam antibiotics and beta-lactamase inhibitors
文献作者:Baltzer,B.; Binderup,E.; von Daehne,W.; Godtfredsen,W.O.; Hansen,K.; Nielsen,B.; Sorensen,H.; Vangedal,S.
参考来源:J Antibiot 1980,33(10),1183-92
合成路线:The condensation of 6-(2-amino-2-phenylacetamido)penicillanic acid sodium salt (I) with benzaldehyde (II) in DMF gives the corresponding imine (III),which is then condensed with iodomethyl penicillanate 1,1-dioxide (IV) in DMF to yield the bisester (V).Finally,this compound is deprotected by means of Girard P reagent and TsOH in methanol to afford the target bis-penicillanate.
参考文献标题:Synthesis of 1,1-dioxopenicillanoyloxymethyl 6-[D-alpha-(benzylideneaminophenylacetamido)]penicillanate and analogs.New intermediates in the preparation of sultamicillin
文献作者:del Pozo,C.; et al.
参考来源:Tetrahedron 2001,57(29),6209
产品链接: CAS No. 76497-13-7››