Yutaka Kameyama

A facile synthesis of C(3)-alkenyl substituted cephems through addition-cyclization of allenecarboxylates derived from penicillin☆

Abstract A short-cut route to cephalosporins bearing alkenyl substituents on the C(3)-position through copper(I) chloride-promoted Michael-type addition of alkenyltributyltins to allenecarboxylates, derived from penicillin, is described.

A convenient synthesis of 2-exo-methylene penam, a potent intermediate for new β-lactam antibiotics synthesis

Abstract A convenient synthesis of 2-exo-methylene penams 1 was performed by transformation of thiazoline-azetidinones, derived from penicillin G, through intramolecular Michael addition. Manipulation of the exo-methylene moiety of 1 opened new entries to 2-oxopenam and 2β-thiomethyl substituted penams, respectively.

Deprotection of carboxylic esters assisted by hydrogen bonding network in phenolic media. Its application to β-lactam antibiotic syntheses

Deprotection of p-methoxybenzyl, diphenylmethyl, and tert-butyl ester groups, which is an essential step of β-lactam antibiotic synthesis, can be performed successfully by gentle heating in phenolic media.

A facile synthesis of 2-exo-methylenepenam; a potent intermediate for syntheses of new β-lactamase inhibitors

A convenient synthesis of 2-exo-methylenepenams 1 is performed by reductive cyclization of allenecarboxylates 8 in a BiCl3/Zn bimetal redox system; subsequent manipulation of the 2-exo-methylene moiety of 1 opens new entries to β-lactam antibiotics and/or β-lactamase inhibitors.

Facile access to 3-allyl- and3-benzyl-Δ3-cephems through reductiveaddition/cyclization of allenecarboxylate with allylic and benzylichalides in an [NiCl2(bipy)]/PbBr2/Al redox system

Sequential reductive addition/cyclization of the allenecarboxylate 1, derived from penicillin G, with allylic and benzylic halides is successfully achieved by the aid of a three-metal redox system consisting of aluminium metal (2.5 molar equiv.) and catalytic amounts of [NiCl2(bipy)] (0.1 molar equiv.) and PbBr2 (0.05 molar equiv.) in N-methyl-2-pyrrolidone (NMP) to afford the corresponding 3-allyl- and 3-benzyl-Δ3-cephems 3a–i in 20–85% yields. The reactions of 1 with vinyl, prop-2-ynyl and phenyl halides in the same three-metal redox system result in the recovery of 1 and/or partial formation of 2-exo-methylenepenam 4. A similar electroreductive addition/cyclization of 1 with allyl bromide is performed by passage of an electrical current (3.2 F mol-1) in an [NiCl2(bipy)]/PbBr2/NMP/(Pt cathode)–(Al anode) system.

2-Substituted penems, new candidates for cephalosporinase inhibitors

Abstract Upon preliminary bioassay experiments, C(2)-substituted penems 5 exhibit promising activities particularly against E. Cloacae (cephalosporinase).