153893-57-3

Upstream product

• 682747-70-2 pivaloyloxymethyl (4R)-{(2R,3S)-3-[(1R)-1-(tert-butyldimethylsilyloxy)ethyl]-4-oxoazetidin-2-y}-3-oxopentanoate 
• 682747-71-3 pivaloyloxymethyl (4R)-{(2R,3S)-3-[(1R)-1-(tert-butyldimethylsilyloxy)ethyl]-4-oxoazetidin-2-y}-2-diaza-3-oxopentanoate 
• 2524-64-3 chlorophosphoric acid diphenyl ester 
• 124667-64-7 (3S,4R)-3-[(R)-1-(t-butyldimethylsilyloxy)ethyl]-4-[(R)-2-imidazol-1-yl-1-methyl-2-oxoethyl]azetidin-2-one 
• 153893-54-0 2-{(R)-2-[(2S,3S)-3-[(R)-1-(tert-Butyl-dimethyl-silanyloxy)-ethyl]-1-(2,2-dimethyl-propionyloxymethoxyoxalyl)-4-oxo-azetidin-2-yl]-propionylsulfanylmethyl}-malonic acid diethyl ester 
• 153492-34-3 2-((R)-2-{(2S,3S)-3-[(R)-1-(tert-Butyl-dimethyl-silanyloxy)-ethyl]-4-oxo-azetidin-2-yl}-propionylsulfanylmethyl)-malonic acid diethyl ester 
• 93711-85-4 (2R)-2-[(2S,3S)-3-{(1R)-1-(t-butyldimethylsilyloxy)ethyl}-4-oxoazetidin-2-yl]propionic acid 
• 183183-69-9 (2S,5R,6S,7S)-7-[(R)-1-(tert-Butyl-dimethyl-silanyloxy)-ethyl]-5-methyl-4,8-dioxo-3-thia-1-aza-bicyclo[4.2.0]octane-2-carboxylic acid 2,2-dimethyl-propionyloxymethyl ester 

Relevant academic research and scientific papers

A new synthesis of 1β-alkylcarbapenems utilizing Eschenmoser sulfide contraction of the novel thiazinone intermediates

Novel syntheses of the 1β-alkylcarbapenems were achieved on the basis of Eschenmoser sulfide contraction via the new bicyclic 1,3-thiazinone intermediates. 1,3-Thiazinones 7, 16, and 25 were effectively prepared from thioesters 5 and 22 using a C4-S bond formation process. The sulfide contraction reactions were performed by treatment of 7, 16, and 25 with base (NaH or KO-t-Bu) in the presence of triphenylphosphine to generate the corresponding carbapenem enolate 12, 17, and 26, which were trapped by (PhO)2POCl followed by the reaction with mercaptans to afford carbapenems 10a, 10b, 19, and 28, respectively.

Novel prodrugs of meropenem with two lipophilic promoieties: Synthesis and pharmacokinetics

To improve the oral absorption of meropenem (MEPM), we synthesized and evaluated a series of its double-promoiety prodrugs, in which lipophilic promoieties were introduced into carboxyl and pyrrolidinyl groups. Among these prodrugs, pivaloyloxymethyl (1R,5S,6S)-2-[(3S,5S)-5-(N,N-dimethylcarbamoyl)-1- (isobutyryloxymethyloxycarbonyl)pyrrolidin-3-ylthio]-6-[(1R)-1-hydroxyethyl] -1-methylcarbapen-2-em-3-carboxylate (4) and 1-ethylpropyloxycarbonyloxymethyl (1R,5S,6S)-2-[(3S,5S)-5-(N,N-dimethylcarbamoyl)-1- (isobutyryloxymethyloxycarbonyl)pyrrolidin-3-ylthio]-6-[(1R)-1-hydroxyethyl] -1-methylcarbapen-2-em-3-carboxylate (8) were chosen for further evaluation. Compounds 4 and 8 were well absorbed after oral administration to rats and beagles (bioavailability 18.2-38.4%), and expected to show potent therapeutic efficacy in patients infected with various pathogens, such as penicillin-resistant S. pneumoniae and β-lactamase-negative ampicillin-resistant H. influenzae.