A3-cephems

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]. 

The change from a A3-cephem to a A2-cephem system increases the rate of alkaline hydrolysis two- to three-fold (Table 5.4.K) [72],... 

C s -lodomethylcephalosporins. C3-Acetoxymethyl- or C3-carbamoylmethylce-phalosporins (1) are converted to C3-iodomethylcephalosporins (2) on reaction with lSi(CH3)3 in CH2C12 at 20°. The ester group in 1 is not cleaved if it is benzyl or t-butyl, but p-methoxybenzyl or benzhydryl esters are cleaved faster than the allylic acetate group. This reaction is observed with both A2- and A3-cephems.5... 

Wolfe S, Hoz T. A semiempirical molecular orbital study of the methanolysis of complex azetidinones. A combined MM and QM analysis of the interaction A2- and A3-cephems with the penicillin receptor. Can J Chem 1994 72 1044-1050. 

To a suspension of 3.0 g of 7-[D-(-)-a-amino-p-hydroxyphenylacetamido]-3-[5-(l-methyl-l,2,3,4-tetrazolyl)thiomethyl]-A3-cephem-4-carboxylic acid in 29 ml of water was added 0.95 g of anhydrous potassium carbonate. After the solution was formed, 15 ml of ethyl acetate was added to the solution, and 1.35 g of 4-ethyl-2,3-dioxo-l-piperazinocarbonyl chloride was added to the resulting solution at 0°C to 5°C over a period of 15 minutes, and then the mixture was reacted at 0°C to 5°C for 30 minutes. After the reaction, an aqueous layer was separated off, 40 ml of ethyl acetate and 10 ml of acetone... 

C(2)-C(3) fused polycyclic cephalosporins have received considerable attention as new candidates for /3-lactam antibiotics. An access to tricyclic cephalosporins based on metal-promoted alkenylation of 3-trifloxy-A3-cephem and subsequent Diels-Alder reaction has been published <1996TL5967>. Alternatively, the reaction of a cephalosporin triflate with silyl enol ethers and silylketene acetals has been described to afford tri- and tetracyclic cephalosporins <1996TL7549>. A related process is the formation of fused polycyclic cephalosporins 27 and 28 bearing a wide range of functionalities from the reaction of cephalosporin triflates 26 with unsaturated compounds (alkenes and alkynes) and a base (Scheme 5) <1997JOC4998>. These studies have suggested that the reaction proceeds via the intermediacy of a six-membered cyclic allene which undergoes concerted nZs + K2a cycloaddition with alkenes and acetylenes. 

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). 

The reaction of 3-(chloromethyl)-A3-cephem 62 with organotins in the presence of copper(l) chloride, and the related copper(0)-promoted coupling reaction of 62 with allyl and benzyl bromides have been investigated <1997JOC3782>. It was found that both reactions could be achieved only in the presence of terpyridine (tpy) or bipyridine (bpy) as a ligand, to afford 3-alkyl-A3-cephems 63 and 3-(arylalkyl)-A3-cephems 64, respectively (Scheme 12). 

Cephaloglycin. 3-[(Acetyloxy>methyl]-7-[carboxylic acid 7-(2-amino-2-phenylacetamido)-3-[Pg.304]

D-(-)-0 -Amino-p-hydroxyphenylacetamido] -3-[5-(1-methyl-1,2,3,4-tetrazolyD-thiomethyl] -A3-cephem-4-carboxylic acid... 

To a suspension of 3.0 g of 7-[D-(-)-0 -amino-p-hydroxyphenyiacetamido] -3-[5-(1-methyi-1,2,3,4-tetrazoiyl)thiomethyl] -A3-cephem-4-carboxyiic acid in 29 mi of water was added 0.95 g of anhydrous potassium carbonate. After the solution was formed, 15 ml of ethyl acetate was added to the solution, and 1.35 g of 4-ethyl-2,3-dioxo-1 -piperazinocarbonyl chloride was added to the resulting solution at 0°C to 5°C over a period of 15 minutes, and then the mixture was reacted at 0°C to 5°C for 30 minutes. After the reaction, an aqueous layer was separated off, 40 ml of ethyl acetate and 10 ml of acetone were added to the aqueous layer, and then the resulting solution was adjusted to a pH of 2.0 by addition of dilute hydrochloric acid. Thereafter, an organic layer was separated off, the organic layer was washed two times with 10 ml of water, dried over anhydrous magnesium sulfate, and the solvent was removed by distillation under reduced pressure. The residue was dissolved in 10 ml of acetone, and 60 ml of 2-propanol was added to the solution to deposit crystals. The deposited crystals were collected by filtration, washed with 2-propanol,and then dried to obtain 3.27 gof 7-[D-(-)-a-(4-ethyl-2 A-dioxo)-1 -piperazinocarbonylamino)-p-hydroxyphenylacetamido] -3-[5-(1 -methyl-1,2,3,4-tetrazolyl)thiomethyl]-A -cephem-4-carboxylic acid, yield 80.7%. The product forms crystals, MP lOO C to lOO C (with decomposition). 

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