- FLUOROGENIC BETA-LACTAMASE SUBSTRATE AND ASSOCIATED DETECTION METHOD
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This invention relates to probes for the detection of β-lactamase-type enzymatic activity. In particular, the invention relates to novel fluorogenic substrates for detecting the presence of a catalytically active β-lactamase and a detection method using such substrates.
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Page/Page column 40; 42-43
(2021/06/04)
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- Preparation method of cefoxitin lactone
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The invention discloses a preparation method of a cefoxitin lactone. The method comprises the following steps: (1) under catalysis of N,O-bis(trimethylsilyl)acetamide or triethylamine, 2-thiopheneacetyl chloride and 7-ACA are subjected to an amidation reaction in an organic solvent to obtain a compound 2; (2) the compound 2 is subjected to a hydrolysis reaction under enzyme catalysis to obtain an[(6R,7R)-3-methylol-8-oxo-7-(2-thiopheneacetamido)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid] compound 1; and (3) the compound 1 is subjected to an intramolecular esterification reaction in an alcohol solvent under the action of an acid, and after the reaction is completed, the cefoxitin lactone is obtained by post-treatment. The preparation method has mild reaction conditions, simpleoperation, and high reaction yield, and the obtained cefoxitin lactone has high purity, and can be used as an impurity reference substance in the process of drug consistency re-research.
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- Progress towards a stable cephalosporin-halogenated phenazine conjugate for antibacterial prodrug applications
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Resistant bacteria successfully evade the action of conventional antibiotic therapies during infection, often leading to significant illness and death. Our lab has discovered halogenated phenazine (HP) analogues which demonstrate potent antibacterial activities through a unique iron-starving mechanism. Herein, we describe synthetic efforts towards a stable cephalosporin-HP conjugate prodrug with the aim of translating HPs into useful clinical agents. Cephalosporin-antibiotic conjugates offer multiple advantages for antibacterial design, including the release of active agents through the targeting of intracellular cephalosporinase following selective ring-opening of the beta-lactam warhead. During these studies, carbonate-linked cephalosporin-HP conjugate 16 was synthesized; however, we were unable to successfully remove the ester group required for cephalosporinase processing. Cephalosporin-HP 16 was then utilized as a probe to investigate the stability of the carbonate linker in antibacterial assays and, as predicted, this compound proved to be inactive against Staphylococcus aureus (MIC > 100 μM). The lack of 16’s antibacterial activity can be attributed to the carbonate linker remaining intact throughout the MIC assay, thus not liberating the active HP moiety. These efforts have led to a more stable cephalosporin-HP conjugate joined through a carbonate linker compared to a highly unstable ether linked analogue we previously reported.
- Xiao, Tao,Liu, Ke,Huigens, Robert W.
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- Synthesizing and purifying method of cefalonium
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The invention discloses a synthesizing and purifying method of cefalonium and belongs to the technical field of medicine production. The method comprises a synthesizing step and a purifying step, wherein the synthesizing step comprises a synthesizing step of a cefalonium intermediate and a synthesizing step of a cefalonium coarse product. The method is characterized by comprising the step of obtaining a cefalonium fine product through the purifying step by means of the synthesizing step of the cefalonium intermediate and the synthesizing step of the cefalonium coarse product by taking D-7ACA as a raw material. The method disclosed by the invention has the beneficial effects that the process is slow in reaction and relatively high in safety; by introducing a catalyst, the reaction time is shortened greatly, and the production efficiency is increased; and the production cost is lowered greatly by successfully replacing 7-ACA by D-7ACA.
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Paragraph 0018; 0019; 0022
(2018/01/09)
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- A head cefoxitin acid synthesis technology
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The invention provides a novel synthesis method of cefoxitin acid. Cefoxitin acid is used as a raw material for synthesizing cefoxitin sodium and belongs to second-generation cephalosporin. The cefoxitin acid has balanced antibacterial spectra and has a strong antibacterial effect on gram-negative bacteria. Due to the existence of 7alpha methoxy in the cefoxitin acid, the hydrolysis action of the cefoxitin acid on beta-lactamase can be reduced greatly, so that the beta-lactamase can exist stably in the cefoxitin acid. In the invention, 3-deacetylase cefoxitin acid which is an intermediate is produced by adopting an enzyme process through two-step continuous reaction, materials react in a mild reaction condition, and the process is simple and is convenient to operate. By adopting the novel synthesis method, time and labor can be saved, and the yield and quality of the product can be improved. Because the two-step reaction is carried out in a water phase at room temperature, the consumption of energy and the discharge of organic wastewater can be reduced greatly. The novel synthesis method meets the requirements of large-scale industrial production.
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Paragraph 0015; 0047-0048
(2017/04/21)
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- Synthesis and total 1H- and 13C-NMR assignment of cephem derivatives for use in ADEPT approaches
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We report the synthesis and total NMR characterization of 5-thia-1-azabicyclo-[4.2.0]oct-2-ene-2-carboxylic acid-3-[[[(4″- nitrophenoxy)carbonyl]oxy]-methyl]-8-oxo-7-[(2-thienyloxoacetyl)amino] -diphenylmethyl ester-5-dioxide (5), a new cephalosporin derivative. This compound can be used as the carrier of a wide range of drugs containing an amino group. The preparation of the intermediate product, 5-thia-1-azabicyclo[4.2.0] oct-2-ene-2-carboxylic acid-3-[methyl 4-(6-methoxyquinolin-8-ylamino) pentylcarbamate]-8-oxo-7-[(2-thienyloxoacetyl)amino]-diphenylmethyl ester-5-dioxide (6), as well as the synthesis of the antimalarial primaquine prodrug 5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid-3-[methyl 4-(6-methoxyquinolin-8-ylamino)pentylcarbamate]-8-oxo-7-[(2-thienyloxoacetyl) amino]- 5-dioxide (7) are also described, together with their total 1H- and 13C-NMR assignments.
- Blau, Lorena,Menegon, Renato Farina,Ferreira, Elizabeth Igne,Ferreira, Antonio Gilberto,Boffo, Elisangela Fabiana,Tavares, Leila Aley,Heleno, Vladimir Constantino Gomes,Chung, Man-Chin
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p. 841 - 854
(2008/09/18)
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