77967-96-5

Upstream product

• 15446-43-2 neamine tetrahydrochloride 
• 1092494-97-7 N-benzyloxycarbonyloxy-5-norbornene-endo-2,3-dicarboximide 
• 3947-65-7 neomycin A 

Downstream Products

• 171366-86-2 1,3,2'-tri-N-(tert-butoxycarbonyl)-6'-N-carbobenzyloxyneamine 
• 401947-23-7 [(1R,2S,3S,4R,5S)-4-((2R,3R,4R,5R,6R)-6-Aminomethyl-3-tert-butoxycarbonylamino-4,5-bis-trimethylsilanyloxy-tetrahydro-pyran-2-yloxy)-5-tert-butoxycarbonylamino-3-hydroxy-2-trimethylsilanyloxy-cyclohexyl]-carbamic acid tert-butyl ester 
• 88985-60-8 6'-N-(benzyloxycarbonyl)-3',4':5,6-di-O-cyclohexylidene-1,2',3-tri-N-tosylneamine 

Relevant academic research and scientific papers

Synthesis and use of sulfonamide-, sulfoxide-, or sulfone-containing aminoglycoside-CoA bisubstrates as mechanistic probes for aminoglycoside N-6′-acetyltransferase

Aminoglycoside-coenzyme A conjugates are challenging synthetic targets because of the wealth of functional groups and high polarity of the starting materials. We previously reported a one-pot synthesis of amide-linked aminoglycoside-CoA bisubstrates. These molecules are nanomolar inhibitors of aminoglycoside N-6′-acetyltransferase Ii (AAC(6′)-Ii), an important enzyme involved in bacterial resistance to aminoglycoside antibiotics. We report here the synthesis and biological activity of five new aminoglycoside-CoA bisubstrates containing sulfonamide, sulfoxide, or sulfone groups. Interestingly, the sulfonamide-linked bisubstrate, which was expected to best mimic the tetrahedral intermediate, does not show improved inhibition when compared with amide-linked bisubstrates. On the other hand, most of the sulfone- and sulfoxide-containing bisubstrates prepared are nanomolar inhibitors of AAC(6′)-Ii.

Conjoint molecules of cephalosporins and aminoglycosides

A general synthetic route to conjoint molecules of cephalosporins and aminoglycosides is described. These molecules were designed as potential substrates for bacterial β-lactamases, enzymes that hydrolyze the β-lactam bond of cephalosporins. Hydrolysis of the β-lactam bond was expected to release the C10-appended aminoglycoside. Since β-lactamases are sequestered in the periplasmic space of gram-negative bacteria, this sequence of events would liberate aminoglycoside inside such bacteria. It is expected that such local delivery of aminoglycosides would circumvent the inherent toxicity of aminoglycosides that occurs during systemic exposure within the mammalian host.