43 ペニシリンよりModified β-lactam Antibioticsへの変換

概要

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The syntheses of new modified β-lactam antibiotics are described. The reaction of disulfide(2a) with nucleophiles in the presence of heavy metal ions leads to new 2β-substituted methyl penicillins(3) and 3β-substituted cephams(5). The same products are also obtained by nucleophilic displacement of 2-bromomethyl penicillin(3a) and 3-bromo-substituted cepham (5a). It seems reasonable to postulate that these reactions proceed via the same intermediate "episulfonium ion(4)". The evidence is described in some details. While, 2-bromomethyl penicillin(3a) is cyclized by strong bases intramolecularly to give a new product(9) which possesses a condensed cyclopropane ring in the molecule. Treatment of (9) with AlBr_3 as a Lewis acid affords a new β-lactam antibiotic (13) as a major product accompanied with a small amount of (14) and (15). However, when TiCl_4 is used, (16) is obtained as a major product. By oxidations of both (15) and (16) with m-chloroperbenzoic acid, a mixture of (17) and (18) is obtained respectively. It is found that various acyl derivatives(20) possess higher antibacterial activities than the corresponding deacetoxy-cephalosporins.
天然有機化合物討論会の論文
1974-10-01