Cephalosporins synthesis

In his cephalosporin synthesis methyl levulinate was condensed with cysteine in acidic medium to give a bicyclic thiazolidine. One may rationalize the regioselective formation of this bicycle with the assumption that in the acidic reaction mixture the tMoI group is the only nucleophile present, which can add to the ketone. Intramolecular amide formation from the methyl ester and acid-catalyzed dehydration would then lead to the thiazolidine and y-lactam rings. The stereochemistry at the carboxylic acid a-... 

Intermediates in penicillin and cephalosporin synthesis 78T1731, X = NR, O 75S547... 

Scientists at Merck developed a cephalosporin synthesis based on the addition of azidoacetyl chloride to 1,3-thiazines (56). Although this gives the incorrect 7a -epimer (57), it could be equilibrated to a mixture of 7-amino epimers (see Section 5.10.3.3) from which the desired 7/3-isomer could be separated and further elaborated to cephalosporins (B-82MI51001). 

Indolizine-2,3-dione (102) was converted by periodate into the /3-Iactam (103), which has been patented as an intermediate in penicillin and cephalosporin synthesis (75JOC1264). 

Cyclizations of alkenic amines and imines using organoiron complexes to generate bicyclic 3-lactams are discussed in Chapter 3.1 of this volume. Examples of heterocyclizations of alkenic NA/-dialkylamine and pyridine derivatives to form cyclic quaternary ammonium salts are cited in the Staninets review.Ic A cyclization of an enol thioether has been used to generate a thiazolidine intermediate used in cephalosporin synthesis (equation 131).262... 

Reductive Removal of C-3 Substituents of Cephalosporins (Synthesis of 3-Methylenecephams)... 

The main aspect for monitoring intracellular components was to find the bottlenecks in cephalosporin synthesis. For this it was important to measure the activities of the relevant enzymes in the biosynthesis. After tests in the past [49, 51] and new investigations [22] it was known that the use of protease inhibitors in the disintegration buffer was necessary for routine analysis of activities in crude material. The expense for such measurements was very high and so the main point was the detection of ACVS- and IPNS-activity. But all other important activities were monitored as well. 

Cephalosporin esters are widely used as intermediates in cephalosporin synthesis and as prodmgs for oral administration of parenteral cephalosporins. These esters undergo reversible base-catalysed isomerisation according to the mechanism shown in Scheme 4.8. A proton in the 2-position is abstracted by a base (B) and the resulting carbanion can be repro-tonated in the 4-postion, giving a A -ester. On hydrolysis, A -cephalosporin esters yield A -cephalosporins, which are biologically inactive. 

Induced stereoselectivity can also be obtained with chiral ketenes. Since most studies have been directed toward the synthesis of /1-lactam antibiotics, cycloadditions of protected aminoketenes have been extensively explored to produce intermediates for penicillin and cephalosporin synthesis and cycloadditions of protected hydroxyethylketenes have been used to produce intermediates for carbapenem synthesis. 

HMIS Health 2, Flammability 2, Reactivity 1 Storage Store in cool, dry place keep tightly closed handle and store under nitrogen keep away from heat and open flame Uses Silylating reagent for carboxylic acids blocking agent penicillin and cephalosporin synthesis... 

Inamoto Y, Chiba T, Kaminura T, Takaya T. FK482, a new orally active cephalosporin synthesis and biological properties. J Antibiot 1988 41 828-830. 

Isoascorbic acid (Na salt) has been converted to oxirane 57 which has been utilized in a cephalosporin synthesis.38 An improved synthesis of the versatile C2-symmetric bis(oxirane) 58 has been described from D-mannose and a series of useful mono and bis(oxiranes) 59-63 has been generated from either D-glucono-5-lactone or L-rhamnonolactone. ... 

Malabarba A, Somma S, Berti M, Cavalleri B (1984) 7-(D, L-a-fluoro-2-thienylacetamido) cephalosporanic acid (L 14655), a new semisynthetic cephalosporin. Synthesis and preliminary biological evaluation. Farmaco 39 1050-1060... 

Penicillin and cephalosporin synthesis by the classical intramolecular amidecoupling route continues to be employed successfully. The bisnorpenicillin V... 

---