- Antibiotic synthesis
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A method of preparing intermediates for carbapenem antibiotics characterized by treating a N-deprotected acetoxy conpound of the formula: STR1 in the presence of a Lewis acid or a silylating agent to yeild an intermediate; and cyclizing the intermediate in the presence of rhodium (II) acetate to form a bicyclic ketoester.
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- Stability and kinetics of degradation of imipenem in aqueous solution
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In weakly acidic solution, the broad-spectrum antibiotic imipenem undergoes complex oligomerization initiated by intermolecular carboxyl group attack on the β-lactam group. In weakly alkaline solution, intermolecular reaction between the β-lactam and formimidoyl groups occurs instead. Both β-lactam and formimidoyl groups also hydrolyze at pH-dependent rates. Complex decomposition schemes were determined in kinetic studies at pH 4.0 and 9.0-9.5 using HPLC and mathematical models. The rates of the several initial reactions, calculated as functions of pH and imipenem concentration by fitting the models to kinetic data, fully account for imipenem decomposition rates throughout the neutral pH range.
- Smith,Dezeny,Douglas
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p. 732 - 740
(2007/10/02)
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- N-acyl derivatives of thienamycin
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Disclosed are N-acyl derivatives of the antibiotic thienamycin having the following structural formula: STR1 wherein R1 and R2 are independently selected from the group consisting of hydrogen and acyl. Such derivatives and their pharmaceutically acceptable salts, are useful as antibiotics. Also disclosed are processes for the preparation of such derivatives, pharmaceutical compositions comprising such derivatives, and methods of treatment comprising administering such derivatives and compositions when an antibiotic effect is indicated.
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- Salts of amino-beta-lactamic acids and process for the preparation thereof
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Amino-beta-lactamic acid salts, having the formula: STR1 wherein: (X-Y) may form a system having from 1 to 3 carbon atoms, with or without double bond, (a) closed, in which: X is an atom selected from among carbon, oxygen, nitrogen and sulphur; Y is methylene; Z is a carboxy, sulphonic or phosphonic group (b) open, which may comprise a double bond, in which: X is an atom of hydrogen or a methyl, hydroxymethyl or thiol group, Y is an acid radical chosen from the group formed by sulphonic, phosphonic and sulphoamidic acid; Z is missing. R is an atom or hydrogen, or a methoxyl or ethoxyl group. R1 is, when present, methyl, acetoxymethyl, acylthiomethyl, such as acetyl and benzoyl derivatives, methoxy, chlorine, carbamoyloxymethyl, azido, azidomethyl (alpha, beta)-thioethylamine or a thiomethyl-heterocyclic derivative of the thiazole, thiadiazole, triazole, tetrazole, oxazole, oxadiazole, pyrimidine and imidazole nuclei. R2 is an atom of hydrogen or a methyl, ethyl, benzyl or phenyl group. m, n may be the same or different and may range from 1 to 4, forming a ring or m=n=O to form an open chain. A process for their preparation is also disclosed.
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- AN ENANTIOSELECTIVE APPROACH TO CARBAPENEM ANTIBIOTICS: FORMAL SYNTHESIS OF (+)-THIENAMYCIN
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An enantioselective synthesis of intermediates in synthesis of thienamycin (15) and epithienamycin-C (16) is described.
- Hart, David J.,Ha, Deok-Chan
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p. 5493 - 5496
(2007/10/02)
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- 3-[1-Hydroxyethyl]-4-carboxymethyl-azetidin-2-one
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In a process for the total synthesis of thienamycin from L-aspartic acid via intermediate III: STR1 there is disclosed a process for preparing III via STR2 wherein R is a protecting group.
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- Process for the preparation of 1-carbapenems and intermediates via trithioorthoacetates
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Disclosed is a process for the total synthesis of 1-carbapenem antibiotics (I) from L-aspartic acid via intermediates II and III: STR1 wherein R is hydrogen, a pharmaceutically acceptable ester moiety or salt cation, or a readily removable blocking group; R6 and R7 are, inter alia, independently selected from the group consisting of hydrogen, alkyl, alkenyl, aryl and aralkyl; R1' is hydrogen or a protecting group; and Ra, Rb and Rc are independently selected from alkyl, aryl and aralkyl.
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- Process for the preparation of (2S)-tetrahydro-2α-methyl-6-oxo-4βα-carboxylic acid
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Disclosed is a process for preparing (2S)-tetrahydro-2α-methyl-6-oxo-4β-amino-2H-pyran-3α-carboxylic acid (I) which is useful in the synthesis of thienamycin. The process proceeds via a stereospecific reduction of the 2-acetyl-3-(R)-α-methylbenzylamino-2-pentenedioic acid diester (II). STR1 wherein R is, α-methylbenzyl, and R1 is lower alkyl having 1-6 carbon atoms or arylalkyl such as benzyl.
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- Process for the preparation of thienamycin and intermediates
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Disclosed is a process for the total synthesis of thienamycin from 4-allylazetidinone (IIIa) via STR1 L-aspartic acid (III): STR2 R=H, blocking group or salt cation.
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- Process for the preparation of thienamycin and intermediates
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Disclosed is a process for the total synthesis of thienamycin from L-aspartic acid via intermediate III: STR1 R=H, blocking group or salt cation.
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