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.

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.

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.

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.

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.