Clavam

The clavams differ from penicillins (based on the penam structure) in two respects, namely the replacement of S in the penicillin thiazolidine ring (Fig. 5.1) with oxygen in the clavam oxazolidine ring (Fig. 5.5 A) and the absence of the side-chain at position... 

The 1-caibapenems (Fig. 5.5C) comprise a new family of fused /3-lactam antibiotics. They are analogues of penicillins or clavams, the snlphur (penicilhns) or o gen (calvams) atom being replaced by carbon. Examples are the olivanic acids (section 2.5.1) and thienamycin and imipenem (section 2.5.2). 

Lactams are a broad class of antibiotics that include penicillin derivatives, cephalosporins, monobactams, carbapenems, and clavams (/8-lactamase inhibitors). The metabolic engineering of penicillin and cephalosporins production has been summarized by several good reviews [71,72], so the focus here is clavulanic acid, which has attracted interest in recent years. 

Tahlan, K., Park, H.U., Wong, A., Beatty, P.H. and Jensen, S.E. (2004) Two sets of paralogous genes encode the enzymes involved in the early stages of clavulanic acid and clavam metabolite biosynthesis in streptomyces clavuligenis. 48, 930-939. 

Carbapenem basic structure Clavam basic structure... 

Scheme 102 Solid-phase synthesis of clavams and oxacephams trough P-lactam intermediate...

The first (3-lactams LE inhibitors were naturally occurring bicyclic compounds, such as clavams and cephalosporins [338], but more recently, synthetic monocyclic (3-lactams have been developed. Time-dependent inhibitors of enzyme HLE, based on the cephem nucleus, have been reported. A series of cephalosporin tert-butyl esters have been examined, and the activity of these compounds has been found to be very sensitive to the C-7 substituents, the greatest activity being showed by small, a-oriented, and electron-withdrawing groups. Additionally, the oxidation... 

An important group of four-membered heterocyclic compounds are the derivatives of the /i-lactam [azetidin-2-one (15)] system. Many of the compounds are biologically active, for example, the monocyclic nocardicins [e.g. (16)] and the bicyclic penicillin and cephalosporin antibiotics [e.g. (17) and (18) respectively], and the -lactamase inhibitors of the clavam group (19). 

Baggaley KH, Brown A and Schofield CJ (1997) Chemistry and biosynthesis of clavulanic acid and other clavams. Nat Prod Rep 14, 309-333. 

Intramolecular N-alkylation under phase-transfer conditions (PTCs) of 236 and 237 having the triisopropylbenze-nesulfonyl (TIBS) protecting groups give the corresponding clavams 238 where R = a-H and /3-H, respectively... 

The peneras were conceived by R.B. Woodward in 1976 as structural hybrids of penicillins and cephalosporins [84]. Unlike the carbapenems and clavams, they are not found in nature. They do however possess important biological properties and have therefore created considerable interest in both their total synthesis and their biological evaluation [85]. 

Edwards RG, Dewdney JM, Dobrzanski RJ, Lee D. Immunogenicity and allergenicity studies on two beta-lactam structures, a clavam, clavulanic acid, and a carbape-nem structure-activity relationships. Int Arch Allergy Appl Immunol 1988 85(2) 184-9. 

The clavams differ from penicillins (based on the penam structure) in two respects, namely the replacement of sulphur in the penicillin thiazolidine... 

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