Carboxamides and hydrazide of glycopeptide antibiotic eremomycin. Synthesis and antibacterial activity.
Carboxamides and hydrazide of glycopeptide antibiotic eremomycin were obtained by a direct reaction of the carboxy group of eremomycin with an appropriate amine or hydrazine using diphenyl phosphorazidate as a condencing agent. Eremomycin hydrazide was also obtained by hydrazinolysis of the eremomycin methyl ester. Use of dicyclohexylcarbodiimide or 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide for amidation led to the corresponding eremomycin ureides. The ESI-MS data indicate that eremomycin and its amides exist as dimers. The carboxamide, methylamide and benzylamide of eremomycin were as active against Gram-positive bacteria as the parent antibiotic, and the methylamide, benzylamide and hydrazide were almost an order of magnitude more active than eremomycin against Staphylococcus epidermidis clinical isolates in vitro. Amide of eremomycin as well as ureides were devoid of histamine liberating properties, which demonstrates that protection of the carboxyl group leads to a decrease in the allergenic properties.
Pavlov
A Y
AY
Institute of New Antibiotics, the Russian Academy of Medical Sciences, Moscow, Russia.
Berdnikova
T F
TF
Olsufyeva
E N
EN
Miroshnikova
O V
OV
Filipposyanz
S T
ST
Preobrazhenskaya
M N
MN
Sottani
C
C
Columbo
L
L
Goldstein
B P
BP
D000577:Amides / Q000138:chemical synthesis* / Q000494:pharmacology*; D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology*; D001386:Azides / Q000138:chemical synthesis* / Q000494:pharmacology*; D002240:Carbohydrate Sequence; D006020:Glycopeptides; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D013212:Staphylococcus epidermidis / Q000187:drug effects
D000577:Amides; D000900:Anti-Bacterial Agents; D001386:Azides; D006020:Glycopeptides; C053759:eremomycin