Carbapenems biological activity

The penicillins and cephalosporins share their mechanism of action, pharmacological effects, clinical effects and also immunologic characteristics. They are called beta-lactam drugs because of their unique lactam ring. This ring is present in the penicillins, the cephalosporins, monobactams and carbapenems. The biological activity depends on the presence and... 

This approach has been applied to the preparation of key intermediates for a number of products with biological activity, such as cyclitols, carbapenems and amino acids101 - 103 132. 

Of the many derivatives prepared, BRL 42715 (31) was the compound with the best overall activity and stability. The enzyme, renal dehydropeptidase I (RDHP) is known to be a major cause of metabolic inactivation of carbapenems, such as imipenem, and penems. Whereas the ethylidene derivative (90c) showed substantial degradation of the biologically active (5R)-enantiomer in the presence of human kidney homogenate, BRL 42715 proved particularly stable, with 68% surviving after I hour s exposure to human kidney [90,91], In addition, BRL 42715 was only moderately bound (68%) to human serum. 

Carbapenems, which are P-lactam antibiotics (pen-ems) that are neither penicillins (penams) nor cephalosporins (cephems), proved to be of clinical significance and scientific interest. The first compound of this new type of P-lactam class was thienamycin [6]. Replacing the sulfur atom with a carbon atom altered the penem ring of thienamycin. All biologically active members of the class contain the unsaturated carbapen-... 

The use of phosphonates in the synthesis of representatives of three important classes of biologically active compounds (carbapenems, triquinanes, and cycli-tols) will be briefly discussed here. 

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. 

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