114409-12-0Relevant articles and documents
Synthesis of (5R)-(Z)-6-(1-Methyl-1,2,3-triazol-4-ylmethylene)penem-3-carboxylic Acid, a Potent Broad Spectrum β-Lactamase Inhibitor, from 6-Aminopenicillamic Acid
Osborne, Neal F.,Atkins, Richard J.,Broom, Nigel J. P.,Coulton, Steven,Harbridge, John B.,et al.
, p. 179 - 188 (2007/10/02)
(5R)-(Z)-6-(1-Methyl-1,2,3-triazol-4-ylmethylene)penem-3-carboxylic acid 34 (BRL 42715) has been prepared from 6-aminopenicillanic acid 4 (6-APA) by short stereoselective and efficient route via the novel intermediate, p-methoxybenzyl (5R,6S)-6-bromopenem-3-carboxylate 17.Elaboration of 6-APA 4 to the azetidinone disulfide 10 by established methodology, followed by reductive formylation provided the crystalline C-4 formylthio-azetidinone derivative 29.Cyclization of the oxalimide 28, obtained by ozonolysis of the formylthio derivative 29, to the crystalline 6α-bromopenem ester 17 was effected by way of the phosphine-mediated carbonyl-carbonyl coupling reaction.Sequential tretment of bromopenem 17 with lithium diphenylamide, 1-methyl-1,2,3-triazole-4-carbaldehyde, and acetic anhydride gave a diastereomeric mixture of acylated bromohydrins 32; reductive elimination of this mixture afforded a separable mixture of (Z)- and (E)-triazolylmethylenepenem esters, 33 and 35 respectively.Lewis acid-mediated deprotection of ester 33 provided (5R)-(Z)-6-(1-methyl-1,2,3-triazol-4-ylmethylene)penem-3-carboxylic acid 34 (BRL 42715) as a crystalline sodium salt monohydrate.The 6-heterocyclilmethylene penems, represented by BRL 42715, are potent inhibitors of bacterial β-lactamases and their combination with an appropriate penicillin or cephalosporin results in good synergistic activity against a broad range of β-lactamase-producing bacteria.
Process for the preparation of penem compounds and intermediates for this preparation
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, (2008/06/13)
Compounds of the general formula I in which, X denotes a halogen atom;, Y denotes a hydrogen atom, a halogen atom, or a moiety of the general formula II Z denotes a halogen atom, a hydroxy group, a substituted hydroxy group, an -S(O)nR5 group, or an -Se(O)mR5 group;, n denotes 0, 1 or 2, preferably 0 or 1;, m denotes 0 or 1;, R3 denotes a hydrogen atom or an organic group;, R4 denotes a hydrogen atom, a carboxy-salt-forming ion, or a carboxy-ester-forming group;, R5 denotes a hydrogen atom, a hydrocarbon group, or a heterocyclyl group; and, R12 denotes a hydrogen atom, an unsubstituted or substituted hydrocarbon group, or an unsubstituted or substituted heterocyclyl group;, are novel intermediates useful in the preparation of 6-methylene-penems of the general formula X:
