Preparation and properties of 5-phenylphenoxymethylpenicillin.
Cycloaddition of azidoacetyl chloride to benzyl D-5,5-dimethyl-5-phenyl-2-thiazoline-4-carboxylate (1a) gave 5-phenyl-6alpha-azidopenicillanate (2a). By catalytic reduction of 2a and reaction with phenoxyacetyl chloride, 5-phenyl-6-epiphenoxymethylpenicillin benzyl ester (4a) was obtained. Oxidation of 4a gave the sulfoxide 6, which was isomerized in the presence of DBN. The sulfoxide 7 with the normal configuration could be isolated but deoxygenation of the sulfoxide was not successful. Isomerization of 4a with DBN, either with or without silylation of the side chain, gave a mixture from which 5-phenylphenoxymethylpenicillin benzyl ester (5) was isolated. Compound 5 was debenzylated to 5-phenylphenoxymethylpenicillin potassium salt (8). The antibacterial activity of 8 was low, whereas  the 6-epimer 9 was inactive. Contary to published information, the 5-phenylpenam derivative 4c could be prepared by the same method.
D007536:Isomerism; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D010404:Penicillin V / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D013210:Staphylococcus / Q000187:drug effects; D013237:Stereoisomerism
C010502:5-phenylphenoxymethylpenicillin; D010404:Penicillin V