Cephems synthesis

R)-amino-3-(1-methyl-1 H-tetrazol-5-ylthio-methyl)-3-cephem-4-corboxylic ocid (cf. cefomondole synthesis)... 

The synthesis of cephem derivative 99 involved S-alkylation of 5-methyl oxadiazoline-2-thione with the appropriate tosylate <2000BMC2317>. 

Morpholine, pyrrolidine and sodium azide can also be also used as nucleophiles in the synthesis of 3-substitututed A3-cephems 515 via the conjugate addition of the 2,3-allenoate moiety in 513 [233]. 

M. Narisada, T. Yoshida, M. Ohtani, K. Ezumi, M. Takasuka, Synthesis and Substituent Effects on Antibacterial Activity, Alkaline Hydrolysis Rates, and Infrared Absorption Frequencies of Some Cephem Analogues Related to Latamoxef (Moxalactam) , J. Med. Chem. 1983, 26, 1577-1582. 

Simple 6H- 1,3-oxazines and -thiazines are commonly encountered as intermediates in the reactions of oxazinium and thiazinium salts with nucleophiles (see Section 2.27.2.2.3). Additionally there is a considerable interest in 6//-1,3-thiazines as intermediates in the synthesis of cephem antibiotics (see Section 2.27.3.24) and many approaches have been... 

The development of efficient routes to synthesize (3-lactams is an area of significant research interest [41 -5]. This has been driven, in large part, by the importance of these molecules as constituents of antibiotics, ranging from penicillin-based substrates to a number of more recently developed compounds (e.g., penems, cephems, monobactams, carbapenems, and trinems) [46-51]. (3-Lactams have also been demonstrated to be important synthons in organic synthesis (Fig. 1) [52,53] and to be monomers in the generation of polyamides [e.g., poly((3-peptides)] [54, 55]. 

Another application of the electrolytic ene-type chlorination is a straightforward synthesis on-chloromethyl-dc/f -cephems 10 from azetidinone 8 derived from natural penicillins, 0). 3-Chloromethyl-substituted cephalosporin antibiotics. They have been prepared by displacement of the acetoxyl group of 3-acetoxymethylcephalosporins with a chlorine atom n). The conversion of 8 to 10 comprises the electrolytic ene-type chlorination 12) of 8 and the ring closure of 9 with base (Scheme 2-3). Apparently, the arenesulfonyl... 

Synthesis of 7(3-[2-(2-aminothiazol-4-yl)-2-(Z)-(trytiloxyimino)acetamido]-3-vinyl-3-cephem-4-carboxylic acid x p-toluenesulfonic acid x 2 N,N-dimethylacetamide (the precursor of Cefdinir) was described in Patent US 6,093,814. 

The synthesis and inhibitory activity toward human leukocyte elastase of new 7a-methoxy and 7a-chloro (2-acyloxymethyl)cephem derivatives have been reported <2001EJM185>. Starting from 4-(/frt-butylcarbonyl)-7/3-amino-3-methyl-A3-cephem 1,1-dioxide 37, a practical and efficient route leading to the synthesis of 4-(/frt-butyl-carbonyl)-7a-methoxy-3-methyl-A3-cephem 1,1-dioxide 38, a key intermediate in the preparation of potent inhibitors of mammalian serine proteinases, has been reported <1998SL322>. The new synthetic pathway has allowed easy access to an array of 7-substituted cephem derivatives such as 39 and 40 (Scheme 6). 

Synthesis of 7-[[Pg.1189]

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