The synthesis and reactions of 4-carbomethoxy β-sultams

✍ Scribed by Michael J. Szymonifka; James V. Heck

• Publisher: Elsevier Science
• Year: 1989
• Tongue: French
• Weight: 323 KB
• Volume: 30
• Category: Article
• ISSN: 0040-4039
• DOI: 10.1016/s0040-4039(00)99145-7

✦ Synopsis

The preparation of 4carbomefhauy-I ,2-thiazetidine-l, l -dimides from carbometw-methanesu2fonyl chioti and imines is described. The ability of p-lactam antibiotics to acylate bacterial cell wall enzymes provides the biochemical basis for their bactericidal action. Although structural analogs of p-la&am antibiotics have been intensively investigated for more than forty years. until quite recently scant attention has been focused on replacement of the azetidinone ring by more reactive entities. 1 The 1.2~thiazetidine-1, l-dioxides are attractive candidates for such a substitution because the pi bond overlap which enhances the stability of p-lactams is unavailable to the analogous p-sultams. The greater chemical reactivity anticipated of the latter has been demonstrated,2 thus encouraging the preparation of p-sultam analogs of P-lactam antibiotics. Previous effort in this area employed synthetic schemes which afforded a very limited range of substituents on the p-sultam nucleus.3

We wish to report that carbomethoxymethanesulfonyl chloride, readily available via chlorination of methyl thioglycolate.4 reacts with a wide variety of aIkyl and aryl imines to afford p-sultams 1 in fair to excellent yield. The ester functionality thus introduced provides access to a number of interesting derivatives, and can, for example. be reduced to the hydroxymethyl sidechain found to be biologically acceptable in the carbapenem series.