P-Lactam compounds

A comprehensive study on the solid-phase synthesis of p-lactam compounds has been reported [102]. In situ generated ketenes reacted with aldimines, immobilized on commercially available solid supports, under mild conditions to generate libraries of p-lactams in good to very good overall isolated yields. Different p-lactam derivatives with various substituents at the C-3 and the C-4 position... 

Frau J, Donoso J, Munoz F, Garcia Blanco F. Theoretical calculations of P-lactam antibiotics. III. AMI, MNDO, and MINDO/3 calculations of hydrolysis of P-lactam compound (azetidin-2-one ring). J Comput Chem 1992 13 681-692. 

Saul Wolfe has made important contributions on a broad range of topics in bioorganic chemistry and many aspects of theoretical organic chemistry. His special interests include the gauche effect,255 P-lactam compounds,256 and isotope effects.257... 

Using the stereodirecting effect shown by the proton of an amide function, several authors have prepared various o.p. sulfoxides with high biological interest, such as the P-lactamic compounds, penicillin and cephalosporin23 (Table 1). 

Huang H, Iwasawa N, Mukaiyama T. A convenient method for the construction of P-lactam compounds from P-amino acids using 2-chloro-l-methylpyridinium iodide as condensing reagent. Chem. Lett. 1984 13 1465-1466. 

The answer may be in discovering more specific mechanism-based P-lactamase inhibitors. It is curious that the best drugs developed so far are also P-lactam compounds (Fig. 6-14). One very interesting inhibitor is penicillanic acid sulfone (sulbactam, Fig. 6-14). This drug acts as a substrate (becomes hydrolyzed) and as an irreversible inactivator of TEM-type P-lactamase (covalently binding to it via molecular cleavage). 

Aztreonam (Azactam) is a monocyclic p-lactam compound (a monobactam) isolated from Chromobacterium violaceum. 

In continuation of the research on solid-phase synthesis of biologically interesting p-lactam compounds towards the development of combinatorial libraries, Mata et al. [102] investigated use of 2-chloro-l-methylpyridinium iodide (Mukaiyama s reagent) as a key reagent for the construction of the p-lactam ring in a stereoselective manner. The popular explanation involves the reaction of ketene B with the imine to form a zwitterionic intermediate D (Scheme 13). Alternatively, it is the activated acid A that acylates the imine to form the zwitterion D by abstraction of proton with... 

Identification of -Lactam Compounds. The enzyme P-lactamase is used to identify penicillin and cephalosporin compounds via targeted cleavage of the P-lactam ring system. It should be noted, however, that certain P-lactam compounds, including cloxacillin, are resistant to -lactamase inhibition. ... 

P-lactam Compound Manufacturer s Reported Detection Limit in Bovine Milk ( xg/l) Penzyme Neogen Delvo-X-PRESS Corporation DSM Ltd USFDA Tolerances in Milk ( xg/l) EU MRLs in Milk ( xg/l)... 

In spite of the existing methods to carry out the ring closure [5c], the carbene insertion reaction developed by the Merck group [7] for the thienamycin synthesis (Scheme 1), seems to be the most efficient procedure for the construction of bicyclic p-lactam compounds. Thermolysis of diazoketone 7 in the presence of rhodium acetate provides the cyclized P-ketoester 8 in excellent yield which can be converted into thienamycin 3 in three steps. 

The most recent entry to bicyclic P-lactam compounds through this approach, has been introduced by Barrett and his coworkers [120] by using an intramolecular Michael type reaction of a Af-silyl p-lactam to a nitroalkene induced by fluoride ion (Scheme 45). Namely, the known P-lactam 299 [32a] readily prepared from CSI addition to 1,5-hexadiene, was protected by using TBDMSCI and DIPEA to produce the p-lactam 300. Subsequent ozonolysis, gave the aldehyde 301. Henry reaction of the aldehyde 301 with (phenylthio)-nitromethane furnished, after dehydration of the resulting nitroaldol, the nitroalkene 302 which smoothly cyclized to the carbapenam 303 in the presence of... 

Within the last decade, the use of homolytic or radical reactions in organic synthesis has aroused increasing interest for carbon-carbon bond formation [125]. This approach has been successfully applied to the synthesis of bicyclic P-lactam compounds which has recently been reviewed [126]. 

Homochiral Azetidinones From Natural P-Lactam Compounds. 631... 

Aidoo KA, Paradkar AS. Alexander DC, Jensen SE Use of recombinant DNA techniques to study the production of P-lactam compounds in Streptomyces ckn/uligerus. Culio VP, Hunter-Cevera JC, Cooper R. Johnson RK, eds. Developments in Industrial Microbiology. Vol. 33. Fredricksbuig, Virginia Society of Industrial Microbiology, 1993 219-236. 

Lipase PS has also demonstrated excellent biocatalytic potential for use in the O-acylation ofhydroxymethylated P-lactam compounds. Lipase PS, much like CAL-B, is capable of catalyzing N-acylation as well as reactions at the carboxylic group of the P-amino ester [27]. 

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