Synthesis of nucleotide antibiotics having N-acyl phosphoramidate linkages.
This paper reports the synthesis of nucleotide antibiotics having N-acyl phosphoramidate linkages. The key reaction, the construction of the N-acyl phosphoramidate linkage was achieved by the reaction of nucleoside 5'-phosphoramidite derivatives with carboxamide derivatives in the presence of 5-(3,5-dinitrophenyl)-1H-tetrazole as a very effective activator. By use of this activator, Phosmidosine was synthesized by condensation of an appropriately protected 8-oxoadenosine 5'-O-phosphoramidite derivative with an N-protected prolinamide derivative. In the case of Agrocin 84, the two P-N bonds were constructed progressively. The N-acyl phosphoramidate linkage at the 5'-position of the ribose moiety was similarly synthesized. After phosphorylation of the amino group of the adenine moiety, a fully protected Agrocin 84 derivative, which would be converted to Agrocin 84, was successfully synthesized.
Moriguchi
T
T
Department of Life Science, Tokyo Institute of Technology, Yokohama, Japan.
Asai
N
N
Wada
T
T
Sekine
M
M
D000227:Adenine Nucleotides / Q000138:chemical synthesis* / Q000737:chemistry; D000577:Amides; D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000737:chemistry; D015195:Drug Design; D007202:Indicators and Reagents; D009711:Nucleotides / Q000138:chemical synthesis* / Q000737:chemistry; D010756:Phosphoric Acids; D011685:Purine Nucleotides / Q000737:chemistry
D000227:Adenine Nucleotides; D000577:Amides; D000935:Antifungal Agents; D007202:Indicators and Reagents; D009711:Nucleotides; D010756:Phosphoric Acids; D011685:Purine Nucleotides; C068885:phosmidosine; C013799:agrocin 84; C011067:phosphoramidic acid