262845-95-4

Upstream product

• 87736-74-1 4-(tert-butyldimethylsiloxymethyl)bromobenzene 
• 262845-98-7 (1R,3R)-N-allyloxycarbonyl-1-(4-azidomethylphenyl)-4-tert-butyldimethylsiloxy-3-hydroxybutylamine 
• 228267-29-6 (3R)-N-allyloxycarbonyl-1-(4-tert-butyldimethylsiloxymethylphenyl)-3,4-O-isopropylidene-3,4-dihydroxybutylamine 
• 228267-30-9 (3 R)-N-allyloxycarbonyl-1-(4-hydroxymethylphenyl)-3,4-O-isopropylidene-3,4-dihydroxybutylamine 
• 228267-28-5 (3R)-1-(4-tert-butyldimethylsiloxymethylphenyl)-3,4-O-isopropylidene-3,4-dihydroxybutylazide 
• 304655-64-9 [(R)-1-(4-Azidomethyl-phenyl)-3,4-dihydroxy-butyl]-carbamic acid allyl ester 
• 262846-33-3 [(1R,3R)-1-(4-Azidomethyl-phenyl)-3,4-dihydroxy-butyl]-carbamic acid allyl ester 
• 262846-31-1 (1R,3R)-N-allyloxycarbonyl-1-(4-tert-butyldimethylsiloxymethylphenyl)-3,4-O-isopropylidene-3,4-dihydroxybutylamine 
• 262846-32-2 (1R,3R)-N-allyloxycarbonyl-1-(4-azidomethylphenyl)-3,4-O-isopropylidene-3,4-dihydroxybutylamine 
• 304655-62-7 (1R,3R)-N-allyloxycarbonyl-1-(4-hydroxymethylphenyl)-3,4-O-isopropylidene-3,4-dihydroxybutylamine 

Downstream Products

• 304655-63-8 allyl (1R,5S,6S)-2-[(3S,5R)-1-allyloxycarbonyl-5-[4-(N-allyloxycarbonylaminomethyl)phenyl]pyrrolidin-3-ylthio]-6-[(R)-1-hydroxyethyl]-1-methyl-1-carbapen-2-em-3-carboxylate 

Relevant academic research and scientific papers

Structure-activity relationships of 1β-methyl-2-(5-phenylpyrrolidin-3-ylthio)carbapenems

Structure-activity relationship studies of 1β-methyl-2-[(3S,5R)-5-(4-aminomethylphenyl)pyrrolidin-3- ylthio]carbapenems, especially those pertaining to the relationship between antibacterial activity and side-chain structure were conducted. These studies suggested that the trans-(3S,5R)-5-phenylpyrrolidin-3-ylthio side-chain and the aminomethyl group at the 4-position of the phenyl ring play a key role in enhancing the antibacterial activity against the MRSA and Pseudomonas aeruginosa strains. In particular, the basicity of a substituent at the 4-position of the phenyl ring were shown to greatly contribute to the antibacterial activity against MRSA and methicillin-resistant Staphyloccocus epidermidis strains. In contrast, the amidine group was shown to lead to potent antibacterial activity against P. aeruginosa strains comparable to that of imipenem, however, a good correlation between the basicity of the 4-substituent and antipseudomonal activity was not observed. In conclusion, the 4-aminomethyl or methylaminomethyl group on the phenyl ring was the best substituent for antipseudomonal activity.

Structure-activity relationships of trans-3,5-disubstituted pyrrolidinylthio- 1β-methylcarbapenems. Part 1:J-111,347 and related compounds

1β-Methylcarbapenems having various 3,5-disubstituted pyrrolidinylthio- side chains at C-2 were designed and synthesized. Evaluation of their antibacterial activities indicated that J-111,347 (1a) is the first example of an extremely broad spectrum antibiotic showing activity against methicillin-resistant Staphylococcus aureus (MRSA) as well as Pseudomonas aeruginosa.

Synthesis of J-111,347, a novel 1β-methylcarbapenem with broad-spectrum antibacterial activity

Synthesis of J-111,347 (1), a new 1β-methylcarbapenem with broad- spectrum antibacterial activity including that against methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa, was achieved via diastereoselective preparation of a side-chain thiol 3 from an optically active (R)3,4-dihydroxybutanal 4.

Discovery of novel trans-3,5-disubstituted pyrrolidinylthio-1β-methylcarbapenems

Novel trans-3,5-disubstituted pyrrolidinylthio-1β-methylcarbapenems were designed and synthesized to provide J-111,347 (1a) as the first example of an exceptionally broad-spectrum antibiotic, showing activity against methicillin-resistant Staphyloccocus aureus (MRSA) as well as Pseudomonas aeruginosa. Further derivation of 1a afforded J-111,225 (2a), J-114,870 (3a), and J-114,871 (3b), which showed improved safety profiles and retained broad-spectrum antibacterial activities. Copyright (C) 2000 Elsevier Science Ltd.