Synthesis of complex nucleoside antibiotics.
Herbicidin B and fully prtected tunicaminyluracil, which were undecose nucleoside antibiotics, were synthesized using a samarium diiodide (SmI2) mediated aldol reaction with the use of alpha-phenylthioketone as an enolate. The characteristics of the SmI2-mediated aldol reaction are that the enolate can be regioselectively generated and the aldol reaction proceeds under near neutral condition. This reaction is proved to be a powerful reaction for the synthesis of complex nucleoside antibiotics. The synthesis of caprazol, the core structure of caprazamycins, was conducted by the strategy including beta-selective ribosylation without using a neighboring group participation and the construction of a diazepanone by a modified reductive amination. Our synthetic route would provide a range of key analogues with partial structures to define the pharmacophore, which can be a lead for the development of more effective anti-bacterial agents.
Ichikawa
Satoshi
S
Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan. ichikawa@pharm.hokudai.ac.jp
Matsuda
A
A
D000241:Adenosine / Q000031:analogs & derivatives / Q000138:chemical synthesis; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis*; D002626:Chemistry, Pharmaceutical / Q000379:methods; D015195:Drug Design; D006575:Heterocyclic Compounds, 3-Ring / Q000138:chemical synthesis; D007454:Iodides / Q000494:pharmacology; D007659:Ketones / Q000494:pharmacology; D008956:Models, Chemical; D009705:Nucleosides / Q000138:chemical synthesis*; D011684:Purine Nucleosides / Q000138:chemical synthesis; D012493:Samarium / Q000494:pharmacology; D014415:Tunicamycin / Q000031:analogs & derivatives / Q000138:chemical synthesis; D014498:Uracil / Q000138:chemical synthesis*
D000900:Anti-Bacterial Agents; D006575:Heterocyclic Compounds, 3-Ring; D007454:Iodides; D007659:Ketones; D009705:Nucleosides; D011684:Purine Nucleosides; C506201:herbicidin B; D014415:Tunicamycin; D012493:Samarium; D014498:Uracil; C013551:herbicidins; D000241:Adenosine; C409809:samarium diiodide