- Improved process for the preparation of carbapenem using carbapenem intermediates and recovery of carbapenem
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The present invention relates to preparing carbapenem intermediates that are useful to produce Ertapenem, Meropenem and Doripenem; and provides an effective process for recovering ertapenem compounds.
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Page/Page column 8
(2011/12/03)
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- AN IMPROVED PROCESS FOR THE PREPARATION OF MEROPENEM
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The present invention provides an improved process for the preparation of methyl carbapenem derivative of formula (I) or its pharmaceutically acceptable salts or hydrates thereof in a pure form.
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Page/Page column 10-12
(2011/12/02)
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- PROCESS FOR THE PREPARATION OF CARBAPENEM COMPOUNDS
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The present invention relates to a process for the preparation of carbapenem compound of Formula (I), wherein P1 is hydrogen or a carboxyl protecting group, P3 is hydrogen or a hydroxyl protecting group, R1 is C1-3 alkyl, and A is selected from a group consisting of a) Formula (II), b) Formula (III), c) Formula (IV), d) Formula (V), e) Formula (VI), f) Formula (VII), wherein P2 is hydrogen or an amino protecting group, R2 and R3 may be same or different and are hydrogen, C1-5 alkyl, optionally substituted aryl, or optionally substituted heteroaryl, and X1 is O or S, or its stereoisomers, or salts thereof.
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- PROCESS FOR THE PREPARATION OF CARBAPENEM COMPOUNDS
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The present invention relates to a process for the preparation of carbapenem compound of Formula (I), wherein P1 is hydrogen or a carboxyl protecting group, P3 is hydrogen or a hydroxyl protecting group, R1 is C1-3 alkyl, and A is selected from a group consisting of a) Formula (II), b) Formula (III), c) Formula (IV), d) Formula (V), e) Formula (VI), f) Formula (VII), wherein P2 is hydrogen or an amino protecting group, R2 and R3 may be same or different and are hydrogen, C1-5 alkyl, optionally substituted aryl, or optionally substituted heteroaryl, and X1 is O or S, or its stereoisomers, or salts thereof.
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Page/Page column 21-23
(2010/04/03)
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- IMPROVED METHOD FOR THE CRYSTALLIZATION OF INTERMEDIATES OF CARBAPENEM ANTIBIOTICS
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The present invention relates to an azetidinone compound extremely useful as a common intermediate for the synthesis of 1β-methylcarbapenem compounds. The present invention provides a crystallization method to obtain a crystal which has a higher quality and a higher stability than a conventional crystal and is excellent in filterability at the time of recovering crystal; an azetidinone compound having a low content of impurity; and an azetidinone compound which has a controlled particle size distribution of crystals and improved handleability and stability. The crystallization is carried out by adding a hydrocarbon solvent to a solution in which an azetidinone compound extremely useful as a common intermediate for the synthesis of 1β-methylcarbapenem compounds is dissolved in the presence of a seed crystal in an amount of 200% by weight or less based on the weight of the azetidinone compound. According to the method, the crystal having a high quality and a high stability and excellent filterability at the time of recovering the crystal can be obtained.
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Page/Page column 10
(2009/01/24)
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- Process for The Preparation of Beta-Lactam Antibiotic
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The present invention relates to a process for the preparation of Meropenem of formula (I) in sterile form and also provides an improved process for the preparation of compound of formula (V), which is an important intermediate in the synthesis of Meropenem.
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Page/Page column 5
(2009/10/30)
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- A PROCESS FOR THE PREPARATION OF THE INTERMEDIATE OF Β-METHYL CARBAPENEM
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A process of preparation of the intermediate of β-methyl carbapenem is disclosed, in which 4-acetylazacyclobutanone as the raw material is firstly reacted with α-bromopropionamide having a big inductive group. Since this reaction is highly stereoselectivity, most of the product is the required parent nucleus of β-methyl carbapenem, a product of β-configuration. Compared with the prior art, the process of the present invention is highly-yielding, cost-effective and can be used for large scale production.
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Page/Page column 15
(2010/11/28)
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- AN IMPROVED PROCESS FOR THE PREPARATION OF BETA-LACTAM ANTIBIOTIC
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The present invention relates to a process for the preparation of Meropenem of formula (I) in sterile form and also provides an improved process for the preparation of compound of formula (V), which is an important intermediate in the synthesis of Meropenem.
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Page/Page column 13
(2008/06/13)
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- Synthesis and structure-activity relationships of 1β-methylcarbapenems with quaternary ammonium side chains
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The synthesis and antibacterial activity of 1β-methylcarbapenems with quaternary ammonium groups at the C-2 position have been studied. Two types of new carbapenem derivatives have been synthesized. These 1β-methylcarbapenems, one type having a (2S,4S)-2-[1,1-dimethyl-2-(1-piperazinyl)carbonyl]pyrrolidinio-4-ylthio group and the other type having a (2S,4S)-2-(4-carbamoylmethyl-4-methylhomopiperazinio-1-ylcarbon-yl)pyrrolidin-4 -ylthio group, show potent and well balanced antibacterial activity as well as high stability against dehydropeptidase-I. The in vivo potency of these two carbapenems was compared with that of meropenem. The structure-activity relationships leading to these carbapenems are also described.
- Ishikawa, Katsuya,Kojima, Katsuhiko,Miyauchi, Masao,Endo, Rokuro,Yasuda, Hiroshi,Kawamoto, Isao
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p. 757 - 770
(2007/10/03)
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- Studies on the synthesis and structure-activity relationships of 2-(2-functionalized pyrrolidin-4-ylthio)-1β-methylcarbapenems
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A series of new carbapenem derivatives, which have a pyrrolidin-4-ylthio group substituted with a hydroxyalkyl or carbamoyl group at the 2′ position as the C-2 side chain, have been prepared. The antibacterial activity and the stability to renal dehydropeptidase-I of these compounds were investigated, and the structure-activity relationships were studied. Among these new carbapenems, (1R,5S,6S)-2-[(2S,4S)-2-{(2-hydroxy)ethylmercaptomethyl}pyrrolidin-4-ylthio]-6- [(1R)-1-hydroxyethyl]-1-methyl-1-carbapen-2-em-3-carboxylic acid (1a) showed the most potent and well balanced activity and was selected as a candidate for further evaluation.
- Lee, Hong-Woo,Kim, Eung-Nam,Son, Hoe-Joo,Ahn, Soon-Kil,Chung, Koo-Hun,Kim, Jung-Woo,Lee, Chong-Ryoul
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p. 2326 - 2330
(2007/10/03)
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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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- Synthetic carbapenem antibiotics III. 1-Methyl thienamycin
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Total syntheses of 1α- and 1β-methyl thienamycin are reported. 1β-Methyl thienamycin retains the antibacterial activity of thienamycin and is highly resistant to hydrolysis by HPD-1 enzyme.
- Shih,Cama,Christensen
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p. 587 - 590
(2007/10/02)
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- Synthetic study of 1-substituted carbapenem antibiotics
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Total synthesis of 1-substituted carbapenems is described. The key step is the reaction of acetoxyazetidinone with ketene silyl acetal.
- Shibata,Iino,Tanaka,et al.
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p. 4739 - 4742
(2007/10/02)
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- SYNTHETIC CARBAPENEM ANTIBIOTICS I. 1-&β-METHYLCARBAPENEM
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A total synthesis of a novel 1-β-methylcarbapenem antibiotic, (-)-(1R,5S,6S)-2-(2-N,N-dimethylamino-2-iminoethylthio)-6--1-methylcarbapen-2-em-3-carboxylic acid 1, is reported.Compound 1 is highly resistant to renal dipeptidase-I yet retains the excellent antibacterial activities of N-formimidoylthienamycin.
- Shih, David H.,Baker, Florence,Cama, Lovji,Christensen, Burton G.
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