Nuclear analogs of β-lactam antibiotics. II. Synthesis of O-2-isocephems

The preparation by total synthesis of a new class of β-lactam antibiotics is reported. Conversion of alcohol 1 b to its mesylate 9 b followed by hydrolysis of the acetal to the enol 1 b and base-catalyzed ring closure gave benzyl 7- β-azido-Δ 3 -O-2-isocephem-4-carboxylate 8 b. Similarly prepared we...

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Bibliographic Details
Published in:Canadian journal of chemistry 1977-02, Vol.55 (3), p.484-507
Main Authors: Doyle, Terrence W, Belleau, Bernard, Luh, Bing-Yu, Conway, Terry Thomas, Menard, Marcel, Douglas, James L, Chu, Daniel Tim-Wu, Lim, Gary, Morris, Leeson R, Rivest, Pierre, Casey, Michael
Format: Article
Language:English
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Summary:The preparation by total synthesis of a new class of β-lactam antibiotics is reported. Conversion of alcohol 1 b to its mesylate 9 b followed by hydrolysis of the acetal to the enol 1 b and base-catalyzed ring closure gave benzyl 7- β-azido-Δ 3 -O-2-isocephem-4-carboxylate 8 b. Similarly prepared were the 3 -methyl, 3 -benzyl, and 3 -phenethyl analogs ( 32 b-d). Reduction of the azides followed by coupling of the resultant amines with phenoxyacetic acid and removal of the benzyl groups by hydrogenolysis gave the acids 35 a-e which exhibited high antibacterial activity. The structural assignments to the O-2-isocephems which were made on the basis of their spectral characteristics (ir, uv, and nmr) are discussed.
ISSN:0008-4042
1480-3291
DOI:10.1139/v77-070