87902-10-1

Upstream product

• 85-44-9 phthalic anhydride 
• 21887-64-9 N₂-(tert-butoxycarbonyl)-L-ornithine 

Downstream Products

• 369656-69-9 [(1S)-1-(1-naphthyl)ethyl]-5-amino-(S)-2-[4-[N-Boc-N-(pyridin-2-ylmethyl)aminomethyl]benzoyl]aminopentanoylamide 
• 1346507-89-8 tert-butyl (2R,3R,4R,5R)-2-((1S,2S,3R,4S,6R)-6-((S)-5-(1,3-dioxoisoindolin-2-yl)-2-hydroxypentanamido)-2-hydroxy-4-tert-butoxycarbonylamino-3-((2R,3R,6S)-3-tert-butoxycarbonylamino-6-((N-(2-(tetrahydro-2H-pyran-2-yloxy)ethyl)tert-butoxycarbonylamino)methyl)tetrahydro-2H-pyran-2-yloxy)cyclohexyloxy)-3,5-dihydroxy-5-methyltetrahydro-2H-pyran-4-yl(methyl)carbamate 
• 1346507-90-1 tert-butyl (2R,3R,4R,5R)-2-((1S,2S,3R,4S,6R)-6-((S)-5-amino-2-hydroxypentanamido)-2-hydroxy-4-tert-butoxycarbonylamino-3-((2R,3R,6S)-3-tert-butoxycarbonylamino-6-((N-(2-(tetrahydro-2H-pyran-2-yloxy)ethyl)tert-butoxycarbonylamino)methyl)tetrahydro-2H-pyran-2-yloxy)cyclohexyloxy)-3,5-dihydroxy-5-methyltetrahydro-2H-pyran-4-yl(methyl)carbamate 
• 1334182-43-2 (S)-Nα-tert-butoxycarbonyl-N-[2-(3,5-dioxo-1,2-diphenyl-1,2,4-triazolidin-4-yl)ethyl]-Nδ-phthaloylornithinamide 

Relevant academic research and scientific papers

An Efficient Synthesis of Optically Pure N δ-Monomethylated l -Arginine and l -Ornithine

N ω-Methylated l-arginines such as asymmetric dimethyl-l-arginine (ADMA) and monomethyl-l-arginine (NMMA) are well-known endogenous modulators of the nitric oxide (NO) generating system. To understand the (patho)physiological role and impact of N δ-methylation of l-arginine and l-ornithine an efficient synthesis of the pure enantiomers was needed. A synthetic approach that furnished both the desired amino acids in 8-10 steps from commercially available N-Boc-l-ornithine in good overall yields (20-21%) and with high optical purity (>99% ee) is reported.

Design, Synthesis, and Bioactivation of O-Glycosylated Prodrugs of the Natural Nitric Oxide Precursor Nω-Hydroxy- l -arginine

Naturally occurring Nω-hydroxy-l-arginine (NOHA, 1) is the best substrate of NO synthases (NOS). The development of stable and bioavailable prodrugs would provide a pharmacologically valuable strategy for the treatment of cardiovascular diseases that are associated with endothelial dysfunction. To improve NOHAs druglike properties, we demonstrate that O-substitution by (glycosylic) acetal formation greatly increased the chemical stability of the hydroxyguanidine moiety and provided a nontoxic group that could be easily bioactivated by glycosidases. A straightforward synthetic concept was devised and afforded a series of diversely substituted prodrugs by O-conjugation of the hydroxyguanidine moiety with different monosaccharides. Systematic exploration of their bioactivation profile revealed that glucose-based prodrugs were more efficiently bioactivated than their galactose counterparts. NOS-dependent cytosolic NO release was quantified by automated fluorescence microscopy in a cell-based assay with murine macrophages. Glucose-based prodrugs performed particularly well and delivered cellular NO levels comparable to 1, demonstrating proof-of-concept.

AMINOGLYCOSIDE DERIVATIVES

The present invention relates to antimicrobial and antibiotic aminoglycoside derivatives. The compounds of the present application have the following chemical structures. The invention also relates to compositions, methods of preparation and methods of treatment of bacterial infections using the above aminoglycoside derivative.