- Precise Preparation of a High-Purity Key Intermediate of Tazobactam
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In situ IR was used to precisely prepare high-purity diphenylmethyl 6α-bromopenicillanate 8, a key intermediate of tazobactam. 8 was obtained when 6α-bromopenicillanic acid 2 reacted with diphenyldiazomethane (DDM). 2 is unstable and must therefore react
- Zhou, Yanan,Wu, Chengjun,Ma, Hongzhi,Chen, Jianchao,Sun, Tiemin
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Read Online
- Enzymatic deprotection of the cephalosporin 3′-acetoxy group using Candida antarctica lipase B
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(Chemical Equation Presented) Cephalosporins remain one of themost important classes of antibiotics. A useful site for derivatization involves generation of and chemistry at the 3′-hydroxymethyl position. While 3′-acetoxymethyl-substituted cephalosporins are readily available, deacetylation to access the free 30-hydroxymethyl group is problematic when the carboxylic acid is protected as an ester. Herein we report that this important transformation has been efficiently accomplished using Candida antarctica lipase B. Although this transformation is difficult to carry out using chemical methods, the enzymatic deacetylation has been successful on gram scale, when the cephalosporin is protected as either the benzhydryl or tert-butyl esters and on the corresponding sulfoxide and sulfone of the tert-butyl ester.
- Patterson, Leslie D.,Miller, Marvin J.
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experimental part
p. 1289 - 1292
(2010/04/29)
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- An improved process for the preparation of diphenylmethyl7β- Phenylacetamido-3-hydroxymethyl-3-cephem-4-carboxylate
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An efficient and improved process for the preparation of diphenylmethyl 7-phenylacetamido-3-hydroxymethyl-3-cephem-4-carboxylate was developed. With the commercially available 7-aminocephalosporanic acid (7-ACA) as starting material, up to 73.5% overall isolated yield of the titled compound was synthesized in two steps via direct phenylacetylation with phenylacetyl chloride, followed by basic hydrolysis and esterification with diphenyldiazomethane. The newly developed process obviated the use of protecting groups, reduced the environmental footprint, and could be easily controlled and conveniently scaled up for this pivotal intermediate in cephalosporin chemistry.
- Keping, Yu,Nan, Sun,Shanzong, Fang,Weimin, Mo,Baoxiang, Hu,Zhenlu, Shen,Xinquan, Hu
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experimental part
p. 815 - 819
(2010/04/22)
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- Syntheses and studies of quinolone-cephalosporins as potential anti-tuberculosis agents
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The syntheses and anti-tuberculosis activity of quinolone-cephalosporin conjugates (1 and 2) are described. Both showed broad-spectrum antibacterial activity and significant anti-TB activity. The carbamate-linked quinolone-cephem 2 showed better antimycobacterial activity, including anti-TB activity, than the direct amine-linked quinolone-cephem 1, while quinolone-cephem 1 was slightly more effective against some Gram-negative bacterial strains.
- Zhao, Gaiying,Miller, Marvin J.,Franzblau, Scott,Wan, Baojie,Moellmann, Ute
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p. 5534 - 5537
(2007/10/03)
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- CEPHEM COMPOUND
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The present invention is concerned with a novel cephem compound, with a process for the production of this compound, which process may contain or consist of fermentative steps, chemical steps, and/or biotransformation steps. A cephem compound according to the present invention characterised by formula (I) or a salt or ester thereof, wherein R is selected from the group consisting of (carboxymethylthio)propionyl (carboxyethylthio)propionyl Y- CH2-CO15 wherein Y is phenyl, phenoxy or tetrazolyl HOOC-X-CO wherein X is defined as (CH2)4 or wherein X is defined as (CH2)P-A-(CH2)q, wherein p and q each individually are 0, 1, 2, 3 or 4, and A is CH=CH, C-=C, CHB, C=O, O, S, NH, the nitrogen optionally being substituted or the sulfur optionally being oxidized, and B is hydrogen, halogen, C1-3 alkoxy, hydroxyl, or optionally substituted methyl, with the proviso that p+q should be 2 or 3, when A is CH=CH or C=-C, or p+q should be 3 or 4, when A is CHB, C=O, 0, S or NH or wherein X is (CH2)m-CH=A-(CH2)n or (CH2)m-C=-C-(CH2)n, wherein m and n each individually are 0, 1, 2 or 3 and m+n = 2 or 3, and A is CH or N, or wherein X is (CH2)p-CH=CH-C H=C-(CH2)q wherein p and q each individually are 0 or 1 and p+q = 0 or 1 and wherein R' is selected from the group consisting of OH O-(alkyl 1-6C) wherein the alkyl can be straight or branched and O-C(alkyl 1-6C)-O-(alkyl 1-6C) wherein the alkyl groups can be straight or branched can inter alia be prepared by fermentative techniques according to the invention and in particular using a suitable microorganism possessing or being transformed with the genes needed for conversion of an appropriate acyl-6-aminopenicillanic acid into the desired compound.
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- An alternative procedure for preparation of cefdinir
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Cefdinir, a broad spectrum third-generation cephalosporin for oral administration, was prepared by the following synthetic pathway: synthesis of diphenylmethyl 7β-amino-3-vinyl-3-cephem-4-carboxylate hydrochloride from 7-aminocephalosporanic acid (7-ACA), preparation of sodium 2-(2-tritylaminothiazol-4-yl)-(Z)-2-(tritylhydroxyimino) acetate from ethyl acetoacetate, coupling of both intermediaries to obtain diphenylmethyl 7β-[2-(2-tritylaminothiazol-4-yl)-(Z)-2-tritylhydroxyimino-3- vinyl-3-cephem-4-carboxylate and final cleavage of trityl and diphenylmethyl protective groups. This procedure allows to obtain better yields of cefdinir and to avoid the use of diketene during the synthesis of this antibiotic by the previously reported method.
- Gonzalez, Maritza,Rodriguez, Zalua,Tolon, Blanca,Rodriguez, Juan C.,Velez, Herman,Valdes, Barbara,Lopez, Miguel A.,Fini, Adamo
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p. 409 - 418
(2007/10/03)
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- The synthesis and evaluation of 3-substituted-7-(alkylidene)cephalosporin sulfones as β-lactamase inhibitors
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A series of 3-substituted-7-(alkylidene)cephaloporin sulfones were prepared and evaluated as inhibitors of representative class A and class C serine β-lactamase. Appropriate substituents resulted in a 1000-fold improvement in the inhibition of the class A enzymes and a simultaneous 20-fold improvement in the inhibition of class C. These new compounds have achieved the goal of creating broad scale inhibitors in the cephalosporin series. (C) 2000 Elsevier Science Ltd. All rights reserved.
- Buynak, John D.,Doppalapudi, Venkata Ramana,Adam, Greg
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p. 853 - 857
(2007/10/03)
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- N,N'-diisopropyl-O-diphenylmethyl isourea: A mild and convenient alklating agent for the formation of cephalosporin derivatives derivatives
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N,N'-Diisopropyl-O-diphenylmethyl isourea reacts with cephalosporin-4- carboxylic acid in tetrahydrofuran at room temperature to give the diphenylmethyl (DPM) ester in good yields without isomerization of the double bond from C-3 to C-2.
- Cha, Kyung Hoi,Kang, Tae Won,Lee, Hong-Woo,Kim, Eung-Nam,Choi, Nam-Hee,Kim, Jung-Woo,Hong, Chung-Il
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p. 2207 - 2211
(2007/10/03)
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- 7β-Amino-cepham-3-ol-4-carboxylic acid compounds
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The invention concerns 7β-amino-cepham-3-ol-4-carboxylic acid compounds, particularly esters thereof, and the N-substituted, especially N-acylated derivatives of such compounds, as well as the 3-O-esters of these compounds. They can be used as intermediates, for example, for the manufacture of the corresponding 3-unsubstituted 7β-amino-3-cephem-4-carboxylic acid compounds, which show outstanding pharmacological effects.
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