PROCESS FOR PREPARING BIS-ESTERS OF 1,1-ALKANEDIOLS COITH 6- -HYDROXY METHYL PENICILLANIC ACID 1,1-DIOXIDE AND -LACTAM ANTIBIOTICS

摘要

Antibiotic esters (I) [R = D-2-amino-2-phenylacetamido or D-2-amino- 2-(-4-hydroxy)acetamido; R1 = H and its acid addn. salts were prepd. Thus, chloromethyl 6,6-dibromopenicillanate was treated with Me3CMgCl in THF at -78≦̸C and later with HCHO to give a mixt. of C-6 epimeric II. Debromination of II by Bu3SNH and then chromatog. sepn. of isomers gave III(R2 = Cl; n = 0), which was oxidized by m-ClC6H4(CO) O2H and treated with NaI in Me2CO to give iodomethyl ester III(R2 = I, n = 2) which was condensated with 6-(D-2-azido-2-phenyl-acetamido) penicillanic acid Na salt and hydrogenated to give I (R = D-2-amino- 2-phenylacetamido). I had β-lactamase inhibiting activity.