Cephalosporin derivatives, preparation

A number of di- and trisubstituted hydrazides of penicillin and cephalosporin derivatives were prepared to study the effect of A-substitution on ease of oxidative cleavage. ... 

In these papers, the carboxylic acid to be protected was a stable, unsubstituted compound. Harsh conditions were acceptable for both formation and cleavage of the amide. Typically, a simple secondary amide is very difficult to cleave. As the pKa of the conjugate acid of an amide decreases, the rate of hydrolysis of amides derived from these amines increases. The dimethylamide of a cephalosporin was prepared as follows using 2,2 -dipyridyl disulfide. ... 

The antibiotic cephalosporin derivative 48 has been reported it was prepared by the coupling reaction of the 1,2,4-thiadiazole acid chloride derivative 46 with the amino cephalosporin derivative 47. Similar cephalosporin derivatives were mentioned in CHEC-II(1996) (Equation 13) <2001JAN364>. 

New cephalosporin derivatives of the sydnones (1) have been prepared and some sydnones (1) useful as anti-inflammatory drugs have been described. ... 

Early examples of successful, highly diastereoselective alkylations of bicyclic /1-lactams include reactions of the enolates from penicillin and cephalosporin derivatives (e.g., 1 and 4). These enolates have also been used in aldol-type additions, acylations and in the preparation of hetero-substituted penicillins and cephalosporins1. 

Thieno[2,3-d]pyrimidines have also been used during the preparation of cephalosporin derivatives (88EUP253507). 

Thienopyrimidyl-2-thioacetamido)cephalosporanic acid derivatives 170 were prepared by reaction of the appropriate 7/3-chloroacetamidoceph-alosporanic acids 169 with the thieno[2,3-d]pyrimidine potassium salts 168 (87PHA160). The 4-methylthio group of quaternized thieno[2,3-d]pyrimi-dine 172 was displaced by the 3-aminomethyl group of cephalosporins 171 to afford cephalosporin derivatives 173 (89AUP584898). 

The synthesis of the carbapenam-3-carboxylic acid 36 <03JA15746> as well as a study on carbapenem biosynthesis have been documented <03JA8486>. The cephalosporin derivative 37 has been prepared and its use as a novel fluorogenic substrate for imaging P-lactamase gene expression demonstrated <03JA11146>. The nucleus of the carbacephem antibiotic loracarbef has been synthesized in a highly efficient and enantioselective fashion from 25,3iS-2-amino-3-hydroxy-6-heptenoic acid, which was derived from enzyme-catalyzed... 

The compound (which had a dihydrothiazine ring fused to the P-lactam core) showed resistance to P-lactamases and was less toxic than benzylpenicillin. The discovery that the basic building block, namely 7-aminocephalosporanic acid (7-ACA), could be synthesised, led to the preparation of numerous cephalosporin derivatives eg cephalothin, cephaloglycin (orally active), cefaclor and cefuroxime (Figure 7). 

The NMR spectrum Fig.2 was obtained by preparing a solution of sodium cephalothin in deuterated water. The spectral assignments shown in Fig. 2 have been discussed in detail by DeMarco and Nagarajan. Interpretation and assignment of the absorption and resonance frequencies to the different atomic features of many cephalosporin derivatives has been discussed. ... 

The metallo-(3-lactamases hydrolyze a series of p-lactam antibiotics, such as penicillin and cephalosporin derivatives. making them harmless to pathogenetic bacteria. Thus, it is important to study the hydrolysis mechanism and prepare a clinically useful inhibitor. According to the three-dimensional structure of a zinc p-lactamase from Bacteroides fraglis, there are two zinc binding sites, where the two zinc ions, Znl and Zn2, are 3.5 A apart and bridged by one hydroxide group and Znl and... 

An environmentally friendly safe method developed for the preparation of 3-carbamoyl cephalosporin derivative such as cefuroxime uses o-transcarbomylase, an enzyme of microbial origin for the conversion of 3-hydroxy function to the desired 3-carbomyl group. This new synthesis replaces the conventional chemical route, which employs hazardous isocyanates such as dichlorophosphenyl isocynate or chlorosulfinyl isocyanate to achieve the same conversion (Scheme 57). ... 

Thiirans.—j8-Hydroxyethyl sulphides give low yields of thiirans when heated with triphenylphosphine. A useful method for the preparation of thiirans is to heat j8-hydroxyethyl sulphenyl chlorides with phosphinesthis mild method is remarkable since olefins are not formed by desulphurization. Hence, treatment of the disulphide (102) with chlorine at 25 °C, followed by treatment with triphenylphosphine gave (103), (60% yield), obtained previously in only 13% yield. The proposed mechanism for the formation of these compounds is shown in Scheme 39. The sequence has been applied to a cephalosporin derivative (Scheme 40) inversion... 

In a similar way, several cephalosporins have been hydrolyzed to 7-aminodeacetoxycephalosporanic acid (72), and nocardicin C to 6-aminonocardicinic acid (73). Penicillin G amidase from Pscherichia coli has been used in an efficient resolution of a racemic cis intermediate required for a preparation of the synthon required for synthesis of the antibiotic Loracarbef (74). The racemic intermediate (21) underwent selective acylation to yield the cis derivative (22) in 44% yield the product displayed a 97% enantiomeric excess (ee). 

Protection of carboxyflc acids and sulfenic acids requires efficient sdyl donors, eg, BSA, MTSA, and bis(ttimeth5isdyl)urea [18297-63-7] (BSU). BSU is often prepared in situ from hexamethyldisda2ane and urea to yield over 90% of the sdylated derivative in synthesis of cephalosporins (5). 

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