- Preparation method of biapenem bulk drug
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The invention provides a biapenem bulk drug preparation method, which comprises: 1) dissolving a biapenem crude product in water at a certain dissolving temperature T1 to prepare a biapenem crude product aqueous solution; (2) controlling the temperature of the biapenem crude product aqueous solution obtained in the step (1) to be T1 or T2, adding activated carbon with stirring for decolorization,filtering the liquid, and cooling the filtrate to T3 for later use; 3) dropwise adding the filtrate obtained in the step 2) into a mixed solvent of acetone and ethanol, which is cooled to T4 in advance, and crystallizing the filtrate; 4) growing crystal; and 5) separating, washing and drying the crystals separated out in the step 4) to obtain the biapenem bulk drug.
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Paragraph 0085-0087
(2020/11/26)
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- AN IMPROVED PROCESS FOR THE PREPARATION OF CARBAPENEM ANTIBIOTIC
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The present invention relates to an improved process for the preparation of Biapenem of Formula (I) having reconstitution time less than 25 seconds. (Formula (I))
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Page/Page column 8
(2013/09/26)
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- New straightforward synthesis and characterization of a unique 1β- methylcarbapenem antibiotic biapenem bearing a σ-symmetric bicyclotriazoliumthio group as the pendant moiety
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Biapenem 1, (1R,5S,6S,)-2-[(6,7-dihydro-5H-pyrazolo[1,2- α][1,2,4]triazolium-6-yl)thio]-6-yl)thio]-6-[(R)-1-hydroxyethyl]-1- methylcarbapen-2-em-3-carboxylate, is a new non-natural 1β-methylcarbapenem antibiotic which exhibits a wide range of antibacterial activity, remarkable chemical stability, and extensive stability against human renal dehydropeptidase-I. Mercaptobicyclotriazolium chloride 2 useful for the pendant moiety of 1 was successfully synthesized starting from hydrazine hydrate 3 along an economically available synthetic route. The thiol 2 was efficiently exploited for an expeditious synthesis of biapenem 1. Characterization (crystal structure, nonbonded S- - -O interaction, conformational analysis, and CH- - -O hydrogen bonds) of 1 was investigated by its X-ray crystallographic, 1H NMR, and deuteration experiment analyses.
- Kumagai, Toshio,Tamai, Satoshi,Abe, Takao,Matsunaga, Hiroshi,Hayashi, Kazuhiko,Kishi, Ikuo,Shiro, Motoo,Nagao, Yoshimitsu
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p. 8145 - 8149
(2007/10/03)
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- Heteroaryliumthio substituted carbapenem derivatives: Synthesis and in vitro activity of 1β-methyl-2-(dihydropyrrolotriazoliumthio)carbapenems
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The syntheses of five thiols, including three dihydropyrrolotriazoliumthiol salts, 1,4-dimethyl-5-mercaptomethyl-1,2,4-triazolium trifluoromethanesulfonate, and 6-mercapto-6,7-dihydro-5h-pyrazolo[1,2-a][1,2,4]triazolium chloride; and the addition of these thiols to 4-nitrobenzyl (IR,5R,6S)-2-(diphenylphosphono)oxy-6-[1(R)-hydroxyethyl]-1-methylcarbapen-2-cm -3-carboxylate and the subsequent hydrogenolysis of the addition products is described. The latter thiol provides a new route towards the preparation of L-627 (LJC 10,627). The compounds were evaluated in vitro against a panel of Gram-positive and Gram-negative bacteria and their antibacterial activities compared with imipenem. The compounds were measured for their hydrolytic stability to dehydropeptidase I (DHP-I) relative to imipenem. The five compounds generally had poorer Gram-positive and Pseudomonas activity than imipenem, although their Gram negative activity was variably improved. The monocyclic triazolium analog was nearly comparable in overall activity to the four bicyclic heterarylium analogs evaluated, including L-627 (LJC 10,627), All compounds were more stable to DHP-I than imipenem, although minor differences existed among them.
- Wildonger,Ratcliffe
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p. 1866 - 1882
(2007/10/02)
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- β-Lactams. 3. Asymmetric Total Syntheis of New Non-Natural 1β-Methylcarbapenems Exhibiting Strong Antimicrobial Activities and Stability against Human Renal Dehydropeptidase-I
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Asymmetric synthesis of 11, the precursor to chiral (3R,4R)-3-ethyl>-4-acetoxyazetidin-2-one (3) was achieved by utilizing a highly diastereoselective aldol-type reaction of acetaldehyde and the chiral tin(II) enolate of 5.Similar diastereoselective alkylations of chiral and achiral tin(II) enolates 13a-d with chiral 3 were also performed to obtain the desired alkylated azetidin-2-ones (17a-d).Compounds 17a,b were successfully converted to new, non-natural 1β-methylcarbapenems 1a and 1b, which exhibited strong and wide-ranging antimicrobial activities and excellent stability against human renal dehydropeptidase-I.
- Nagao, Yoshimitsu,Nagase, Yunosuke,Kumagai, Toshio,Matsunaga, Hiroshi,Abe, Takao,et al.
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p. 4243 - 4249
(2007/10/02)
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