[Development of new synthetic methods and their application to synthesis of useful compounds].
Development of novel synthetic methodologies and their application to synthesis of natural products are described. The first topic is about an extension of the scope of our indole synthesis by radical cyclization of o-alkenylphenyl isocyanides. By utilizing this methodology and nitrogenzenesulfonamide chemistry, an efficient total synthesis of hexacyclic aspidosperma indole alkaloid, aspidophytine, was accomplished. As the second generation indole synthesis, we then developed the method by radical cyclization of o-akenylthioanilides. Synthetic utility of this method was fully demonstrated by a total synthesis of iboga alkaloid, catharanthine. Furthermore, a total synthesis of vinca alkaloid, vinblastine through a practical synthesis of vindoline was achieved, in which the stereochemistry of the crucial coupling reaction of two indole fragments could be completely controlled. In addition to the indole chemistry, exceptionally mild transformations of thiol esters to ketones and alkenyl ketones have been developed. Examples of application of the protocols for the synthesis of natural products are also described.
Tokuyama
Hidetoshi
H
Graduate School of Pharmaceutical Sciences, PRESTO, Japan Science and Technology Corporation (JST), University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. tokuyama@mol.f.u-tokyo.ac.jp
D000447:Aldehydes / Q000138:chemical synthesis; D000470:Alkaloids / Q000138:chemical synthesis*; D001710:Biotin / Q000138:chemical synthesis; D002625:Chemistry, Organic / Q000379:methods*; D003500:Cyclization; D004952:Esters; D006576:Heterocyclic Compounds, 4 or More Rings / Q000138:chemical synthesis*; D026121:Indole Alkaloids; D007211:Indoles / Q000138:chemical synthesis*; D007659:Ketones / Q000138:chemical synthesis; D008299:Maleic Anhydrides / Q000138:chemical synthesis; D009570:Nitriles; D013438:Sulfhydryl Compounds; D014747:Vinblastine / Q000138:chemical synthesis
D000447:Aldehydes; D000470:Alkaloids; C104957:CP 263114; D004952:Esters; D006576:Heterocyclic Compounds, 4 or More Rings; D026121:Indole Alkaloids; D007211:Indoles; D007659:Ketones; D008299:Maleic Anhydrides; D009570:Nitriles; D013438:Sulfhydryl Compounds; C476906:aspidophytine; D014747:Vinblastine; D001710:Biotin