Lactams compounds

Cephalosporin 5-oxides and penicillin 5-oxides (221) can be converted into isothiazol-3-ones (222) by the action of bases. These reactions proceed via an intermediate azetidinonesulfenic acid (223 Scheme 37) (77SST(4)339). Attempts to prepare /3-lactam compounds from isothiazoles have, as yet, been unsuccessful (81X2181). 

Some optically active compounds have been studied [54], The benzazepinone diacid (CGS 12831, 27) was found to have the best in vitro inhibitor potency in a series of lactam compounds, but it showed only marginal biological activity following oral administration, presumably because of poor absorption. The corresponding monoethyl ester (CGS 14824A, 28) was much more potent in vivo [54, 56]. This compound (28) was found to produce dose-dependent antihypertensive effects in conscious normotensive and spontaneous hypertensive rats, generally similar to those produced by enalapril. Evaluation of (28) in healthy volunteers [57, 58] shows that it is an effective,... 

An interesting example of MIP-LC analytics was presented in a paper, which focused on the separation of antibiotics of similar structures. Columns are (commercially) available to separate penicillins ( 3-lactams) from other antibiotics. However, if the quantification of each of the 3-lactam compounds is required, a more selective stationary phase has to be found. Molecular imprinting allows the fabrication of phases specifically for each 3-lactam. If for instance the concentration of the P-lactam oxacillin in a food sample has to be selectively determined, a polymer imprinted with oxacillin is the right choice. Compared to a standard stationary phase, which only allowed the separation of the entire group of (5-lactams from other non-(3-lactam analytes (e. g., bacitracin), the MIP enables the separation of the imprinted species from the pair of non-imprinted 3-lactams penicillin V and penicillin G see Fig. 6 [29,30]. 

M. Galleni, G. Amicosante, J. M. Frere, A Survey of the Kinetic Parameters of Class C beta-Lactamases. Cephalosporins and Other beta-Lactam Compounds , Biochem. J. 1988, 255, 123-129. 

A variety of cyclic products have been prepared from educts containing carbonyl as well as carboxylic groups. Thus, Hanusch-Kompa and Ugi prepared a large number of five-membered cyclic gamma-lactam compounds like 44 from levulinic acid. Other carbonylic acids can lead to compounds like 45, which is made from phthalaldehyde acid, valine methylester, and tert-butylisocyanide. The products like 46 and 47 can result from the U-4CR and further cyclization. 

The penicillins share features of chemistry, mechanism of action, pharmacology, and immunologic characteristics with cephalosporins, monobactams, carbapenems, and -lactamase inhibitors. All are 3-lactam compounds, so named because of their unique four-membered lactam ring. 

Except for oral amoxicillin, penicillins should be given 1-2 hours before or after a meal they should not be given with food to minimize binding to food proteins and acid inactivation. Blood levels of all penicillins can be raised by simultaneous administration of probenecid, 0.5 g (10 mg/kg in children) every 6 hours orally, which impairs renal tubular secretion of weak acids such as 3-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... 

Lactam compounds variously substituted at C-3, C-4, and N-l were reported, more recently, as useful inhibitors of tryptase, and thrombin [371, 372]. 

Fig. 14 Some representative large heterocycles accessible from (3-lactam compounds...

The ester enolate-imine condensation, also called Gilman-Speeter reaction, is another well-accepted method for (3-lactam synthesis (Scheme 4) [67-69]. In 1997, Tomioka reported the first example of a direct catalytic enantioselective synthesis of (3-lactam by using this method [70]. The active reagent is a ternary complex (comprising LDA, the ester enolate, and tridentate amino diether), which finally affords the (3-lactam compounds in high yields and good ee values. 

In continuation of the research on solid-phase synthesis of biologically interesting (3-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 (3-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... 

Eli Lilly (Indianapolis/IN, USA) needed a p-nitrobenzyl esterase to hydrolyze the p-nitrobenzyl ester of a )3-lactam compound in DMF. The purely organic route with zinc salts and large amounts of organic solvent was unattractive, so an enzyme was sought which could hydrolyze the ester. One with rather low activity was found which served as a starting point for directed evolution. As nature never had to hydrolyze an antibiotic in DMF, this approach seemed very promising. 

Brakhage A (1999) Biosynthesis of -lactam compounds in microorganisms. Comprehensive Natural Products Chemistry, Vol 4. Elsevier, Amsterdam, pp 159-193. 

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... 

Gray et al. (G3) have identified the products of alkaline potassium permanganate oxidation of bilirubin by chromatographic comparison with authentic compounds. The only compound obtained was 4-methyl-3-carboxyethylpyrrole-2,5-dicarboxylic acid, and they have therefore concluded that bilirubin is a lactam compound and in common with other bile pigments has a IXa structure (Fig. 2). 

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). 

There are two ways of obtaining chiral substances using a chiral crystal environment. One is to produce the chiral compounds from the prochiral ones, and the other is to obtain the chiral compounds from racemic ones. The former method is called absolute asymmetric synthesis, since the asymmetry is introduced from the physical conditions such as the chiral crystal environment. Several examples [ 1 -7] have been reported since the first example of the chiral polymer produced in the photopolymerization of the chiral monomer crystal [8]. We also observed that chiral 3-lactam compounds were produced from the prochiral oxoamide crystals [9,10]. 

Preparation of f -amino ketones and f -amino esters which lead to f -lactam compounds involves the reaction of imines with enolates catalyzed by Ln(OTF>3, where Ln = Y, Yb, Sc. 

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