• DOI:10.1021/JM00239A009
• Corpus ID: 12007114

Preparation and properties of 5-phenylphenoxymethylpenicillin.

@article{Vanderhaeghe1975PreparationAP,
  title={Preparation and properties of 5-phenylphenoxymethylpenicillin.},
  author={Hubert Vanderhaeghe and Jozef Thomis},
  journal={Journal of medicinal chemistry},
  year={1975},
  volume={18 5},
  pages={
          486-90
        }
}

• H. Vanderhaeghe, J. Thomis
• Published 1 May 1975
• Chemistry, Biology
• Journal of medicinal chemistry

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.