Lactam activation

Fig. 27 [S-Lactam activity-based probes inspired by commercial drugs...

The synthesis of BOA-N-P-D-glucoside starting from BOA, a very unreactive glucosyl acceptor, was only achieved by using a modified Vorbriiggen protocol [190]. BOA was silylated with N,0-bis-trimethylsilyl-trifluoroacetamide at 110 °C for lactam activation. 

Polymerization via monomer anions without added activator behaves quite differently. In this case, theo>-amino acyl lactam activator is first formed in a slow reaction, and then, the polymer chain is started in a fast subsequent reaction. Further a>-amino acyl lactam molecules are formed continuously during the polymerization. Only when all base molecules react with monomer molecules before the other monomer molecules are consumed by formation of polymer chains is the degree of polymerization given by the ratio of monomer to base concentration. Since this is mostly not the case, there is no relationship between the ratio [monomer]/[base] and the degree of polymerization. Similar relationships occur for the polymerization of iV-carboxy anhydrides of a-amino acids with strong bases. 

In synthetic target molecules esters, lactones, amides, and lactams are the most common carboxylic acid derivatives. In order to synthesize them from carboxylic acids one has generally to produce an activated acid derivative, and an enormous variety of activating reagents is known, mostly developed for peptide syntheses (M. Bodanszky, 1976). In actual syntheses of complex esters and amides, however, only a small selection of these remedies is used, and we shall mention only generally applicable methods. The classic means of activating carboxyl groups arc the acyl azide method of Curtius and the acyl chloride method of Emil Fischer. 

First the protected oligopeptide is coupled with polymer-bound nitrophenol by DCC. N"-Deblocking leads then to simultaneous cycliiation and detachment of the product from the polymer (M. Fridkin, 1965). Recent work indicates that high dilution in liquid-phase cycli-zation is only necessary, if the cyclization reaction is sterically hindered. Working at low temperatures and moderate dilution with moderately activated acid derivatives is the method of choice for the formation of macrocyclic lactams (R.F. Nutt, 1980). 

ANTTBIOTTCS - BETA-LACTAMS - BETA-LACTAMASE INHIBITOR] (Vol 3) -macrolide activity against [ANTIBIOTICS - MACROLIDES] (Vol3)... 

Synthetic utility of stereoselective alkylations in natural product chemistry is exemplified by the preparation of optically active 2-arylglycine esters (38). Chirally specific a-amino acids with methoxyaryl groups attached to the a-carbon were prepared by reaction of the dimethyl ether of a chiral bis-lactam derivative with methoxy arenes. Using SnCl as the Lewis acid, enantioselectivities ranging from 65 to 95% were obtained. 

Antibiotics have a wide diversity of chemical stmctures and range ia molecular weight from neat 100 to over 13,000. Most of the antibiotics fall iato broad stmcture families. Because of the wide diversity and complexity of chemical stmctures, a chemical classification scheme for all antibiotics has been difficult. The most comprehensive scheme may be found ia reference 12. Another method of classifyiag antibiotics is by mechanism of action (5). However, the modes of action of many antibiotics are stiU unknown and some have mixed modes of action. Usually within a stmcture family, the general mechanism of action is the same. For example, of the 3-lactams having antibacterial activity, all appear to inhibit bacterial cell wall biosynthesis. 

In common with the naturally occurring carbapenem thienamycin (2), the introduction of the /n j -6-[l-(R)-hydroxyethyi] group had a profound effect on the biological properties of the penems. This, together with an indication from an early study (93) that, as with other P-lactams, the 5(R)-enantiomer was solely responsible for antibacterial activity, provided impetus for the development of methods for the synthesis of chiral penems. 

C QHyN O SNa, as a potentially useful P-lactamase inhibitor capable of potentiating the activity of a number of clinically important P-lactam antibiotics against resistant strains (153). 

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