Mono-bactams

Interestingly, the formation of dimers and trimers by intermolecular aminolysis has also been observed in concentrated solution (>1%) of the mono-bactam aztreonam (5.8) [124],... 

The large family of p-lactams comprises penicillins, cephalosporins, cephamycins, mono-bactams, carbacephems and carbapenems and are so named since they all containing the p-lactam moiety. 

It is probable that the largest number of medicinally directed semi-synthetic agents ever produced containing a specific pharmacophore, the -lactam ring, are the penicillins, cephalosporins and mono-bactams. To these must also be added the synthetic cephems and cephams and the many variations upon those basic themes. Although current figures are not available, it was estimated in 1980 that over 10000 variations on the basic penicillin structure had been made and assayed for their ability to inhibit microbial growth (Hoover, J.R.E., personal communication). 

Miller s hydroxamate method [41], widely used for the preparation of mono-bactams, surprisingly scores a single application useful for penem synthesis [42]. Chiral 0-butyl hydroxamate 91 was prepared by aldol reaction of crotonalde-hyde with synthon 90a (Sn(OTf )2/iV-ethylmorpholine), followed by temporary 0-TBDMS protection of obtained 90b and displacement with butoxyamine. Lactamization of 91 under Mitsunobu conditions (PPh3/DEAD) afforded 92, an equivalent (by alkene oxidative cleavage and deprotection) of enantiomerically pure 4-acetoxyazetidinone. 

A similar observation was recently made for peptide analogs of mono-bactams [173] (Scheme 99). The N-sulphonylamide 322 shows no antibacterial activity in vitro and no inhibitory activity against soluble D,o-peptidases and P-lactamases [136]. However, the zwitterion 323 inhibits E. cloacae P-lactamase at 1 mM concentration. 

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