[Synthetic study of nucleoside antibiotics].
Some of nucleoside antibiotics include complex structures as well as sensitive functionality, which are challenging targets for organic chemists. Among complex nucleoside antibiotics, there are also good drug candidates because they possess a variety of interesting biological properties. Herbicidin B and fully protected tunicaminyluracil, which were undecose nucleoside antibiotics, were synthesized using a samarium diiodide (SmI(2)) mediated aldol reaction with the use of alpha-phenylthioketones as enolate sources. The characteristics of the SmI(2)-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, Sapporo, Japan. ichikawa@pharm.hokudai.ac.jp
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis*; D001381:Azepines / Q000138:chemical synthesis; D002625:Chemistry, Organic; D007454:Iodides; D009705:Nucleosides / Q000138:chemical synthesis*; D055601:Organic Chemistry Phenomena; D011684:Purine Nucleosides / Q000138:chemical synthesis; D012493:Samarium; D014498:Uracil / Q000031:analogs & derivatives* / Q000138:chemical synthesis; D014529:Uridine / Q000031:analogs & derivatives / Q000138:chemical synthesis
D000900:Anti-Bacterial Agents; D001381:Azepines; D007454:Iodides; D009705:Nucleosides; D011684:Purine Nucleosides; C512216:caprazol; C514546:tunicaminyluracil; D012493:Samarium; D014498:Uracil; C013551:herbicidins; C409809:samarium diiodide; D014529:Uridine