Showing papers on "Thienamycin published in 1990"

Studies on lactams. Part 84. .beta.-Lactams via .alpha.,.beta.-unsaturated acid chlorides: intermediates for carbapenem antibiotics

Abstract: Stereocontrolled synthesis of α-vinyl β-lactams and their transformation to convenient intermediates for PS-5, PS-6, asparenomycin, and thienamycin are described

A novel ring-closure strategy for the carbapenems: the total synthesis of (+)-thienamycin

Abstract: Intramolecular Michael cyclization of an N-[(alkoxycarbonyl) methyl]-4-(3-nitro-2-propenyl)-3-oxoazetidin-2-one available in optically pure form leads to the corresponding carbapenam skeleton. Further elaboration via oxidative cleavage of an exocyclic nitromethylene group gives an advanced intermediate, which was transformed into (+)-thienamycin. The stereochemistry of the Michael cyclization and the pitfalls of protective group chemistry are discussed

Synthesis of optically active ene carbamates from chromium carbene complexes : use in palladium(II)-assisted synthesis of relays to (+)-thienamycin

Abstract: Attempts to prepare optically active chromium carbene complexes containing the oxazolidinone moiety led instead to an efficient and general synthesis of optically active ene carbamates. One of these has been subjected to palladium(II)-assisted carboacylation, and complete control of stereochemistry was observed. This compound was converted to a key relay to (+)-thienamycin in good chemical and very high optical yield

A method for the synthesis of alkynyl phenyl sulfides from alkynyltrimethylsilanes. A novel, efficient synthesis of the thienamycin intermediate from 3(R)-hydroxybutyric acid

Abstract: The mechanism of the one-pot conversion of β-amino thiol esters of type 3 to β-lactams of type 4 has been clarified, and it is proposed that the actual active species is a PhSSPh-CuOTf complex. Through the use of this novel reaction, an efficient synthesis of the thienamycin intermediate 2, starting with 3(R)-hydroxybutyric acid, has been achieved

Phagocytic function and antibody-dependent cellular cytotoxicity of human neutrophils in the presence of N-formimidoyl thienamycin.

Abstract: The efficacy of an antibiotic in the treatment of bacterial infections depends upon the interactions of the drug, bacteria and phagocytes. We have studied “in vitro” the effect of N-formimidoyl thienamycin (Imipenem), a novel β-lactamic antibiotic, on the phagocytic function and antibody-dependent cellular cytotoxicity of human neutrophil leukocytes. The incubation of these cells with 50 μg/ml of Imipenem similar to the therapeutic levels reached in plasma results in an increase of their adherence capacity to nylon fiber and to substrate, induced mobility or chemotaxis, opsonization, phagocytosis ofCandida albicans (with serum, with decomplementarized serum and without serum) and latex beads, candidicidal power and the capacity of NBT reduction. Imipenem at this dose also presents chemoattractant power for neutrophils and enhances the antibody-dependent cellular cytotoxicity (ADCC).

Carbapenem antibacterial agents

Abstract: PURPOSE: To provide novel compounds useful as antibacterial agents having more antibacterial activity than thienamycin and stable to dehydropeptitase enzyme. CONSTITUTION: By treating a carbapenem intermediate of formula II with an excess of silver trifluoromethan-sulfonate in an acetonitrile at a low temperature, a compound of formula I [wherein R represents H or CH 3 ; R 1 and R 2 are each H, CH 3 -, CH 3 CH 3 - or the like; R 4 and R a and R b are each H, -CF 3 , halogen, OH or the like; Y represents COOH, COOM (wherein M represents alkaline metal) or the like], for example (5R,6S)-2-(4-[3-(2-piperidonyl)- aminomethyl]phenyl)-6-[1R-hidroxyethyl]carbapene-2-em-3-carboxylic acid, is provided. COPYRIGHT: (C)1994,JPO

Recent Advances in the Synthesis of PS-5 and PS-6 Antibiotics and Related Carbapenem Compounds

Abstract: Carbapenem antibiotics represented by PS-5, PS-6 and thienamycin, have attracted a great deal of interest because of their applications from both a biological and a synthetic point of view. Since several reviews have already appeared concerning isolation, structure determination, total synthesis and biological aspects of these compounds with emphasis on thienamycin, the scope of this review is to underline the most recent advances on the synthesis of PS-5 and PS-6 carbapenems and related compounds according to those strategies involving prior construction of an azetidinone ring suitable for further chemical elaboration. For this purpose four types of reactions have been selected, the chlorosulphonylisocyanate-alkene approach, the acid chloride-imine method, the ester enolate-imine condensation and the hydroxamate approach. Some recent examples on the construction of the bicyclic carbapenem ring system will be briefly discussed in order to illustrate new synthetic perspectives in β-lactam chemistry.

Chemistry of O-silylated ketene acetals: a stereoselective synthesis of chiral thienamycin intermediate

Abstract: A stereoselective synthesis of chiral thienamycin intermediate (10) involving a diastereoselective Michael addition and a silicon-induced Pummerer-type reaction is described.

1-Oxacephems with the Thienamycin-Type Side Chain(1). Synthesis and Antibacterial Activity of 7a-[(1R)-1-Hydroxyethl]1-1oxacephems Bearing Electron-Withdrawing Groups

Abstract: 1-Oxacephem derivatives, 2a-d, bearing the hydroxyethyl group at C 7α and some electron-withdrawing groups at C 3 were synthesized and tested for antibacterial activity. It was found that some of these compounds, in particular, 7α-hydroxyethyl-3-cyano-1-oxacephem 2d, exhibited antibacterial activity, although the potency was low. Some 7α-hydroxyethyl-2-oxo-1-oxacephems, 1a,b, were also prepared and found biologically inactive

A highly stereoselective formal synthesis of (±)-thienamycin through organocopper enolate–iminoester condensation

Abstract: The conjugate addition of the Fleming silylcuprate reagent to methyl crotonate and enolate trapping by methyl 4-methoxyphenyliminoacetate produced a high yield of (1′S*,3R*,4S)-3-[1-(dimethylphenylsilyl)ethyl]-4-methoxycarbonyl-1-(4-methoxyphenyl)azetidin-2-one as a (±)-thienamycin building block.

Optically active olefin lactone derivative and production thereof

Abstract: NEW MATERIAL:An optically active olefin lactone derivative expressed by formula I (R is protecting group of COOH). EXAMPLE:6(R)-5-Carbomethoxy-6-methyl-3,6-dihydro-2H-pyran-2-one. USE:An intermediate capable of industrially and advantageously producing thienamycin (antibiotic substance). PREPARATION:A compound expressed by formula II (R is protecting group of COOH) is asymmetrically hydrogenated in the presence of a ruthenium- BINAP catalyst to provide a compound expressed by formula III, which is then thermally reacted in the presence of an acid catalyst to carry out lactonization and dehydration and afford the compound expressed by formula I. Furthermore, thienamycin expressed by formula VI can be industrially and advantageously produced by passing the above-mentioned compound through compounds expressed by formulas IV and V (R is alkyl, phenyl or aralkyl which may have a substituent group).

Synthesis of a Potential Intermediate to β-Lactam Antibiotics.

Abstract: Cycloaddition of nitrone (2) to α-chloroacrylonitrile followed by hydrolysis afforded the isoxazolidinone (1) as a single diastereomer. The configuration at the new chiral centre (3S), corresponding to that in thienamycin, was established by an X-ray analysis of (9).

A Novel Ring-Closure Strategy for the Carbapenems: The Total Synthesis of (+)-Thienamycin.

Abstract: Intramolecular Michael cyclization of an N-[(alkoxycarbonyl) methyl]-4-(3-nitro-2-propenyl)-3-oxoazetidin-2-one available in optically pure form leads to the corresponding carbapenam skeleton. Further elaboration via oxidative cleavage of an exocyclic nitromethylene group gives an advanced intermediate, which was transformed into (+)-thienamycin. The stereochemistry of the Michael cyclization and the pitfalls of protective group chemistry are discussed

Synthesis of Optically Active Ene Carbamates from Chromium Carbene Complexes: Use in Palladium(II)-Assisted Synthesis of Relays to (+)-Thienamycin.

Abstract: Attempts to prepare optically active chromium carbene complexes containing the oxazolidinone moiety led instead to an efficient and general synthesis of optically active ene carbamates. One of these has been subjected to palladium(II)-assisted carboacylation, and complete control of stereochemistry was observed. This compound was converted to a key relay to (+)-thienamycin in good chemical and very high optical yield

Chemistry of O-Silylated Ketene Acetals: A Stereoselective Synthesis of Chiral Thienamycin Intermediate.

Abstract: A stereoselective synthesis of chiral thienamycin intermediate (10) involving a diastereoselective Michael addition and a silicon-induced Pummerer-type reaction is described.