Tokuyama Hidetoshi
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.
Yakugaku Zasshi. 2003 Dec;123(12):1007-21. doi: 10.1248/yakushi.123.1007.
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.
描述了新型合成方法的开发及其在天然产物合成中的应用。第一个主题是关于通过邻烯基苯基异氰化物的自由基环化扩展我们吲哚合成的范围。通过利用这种方法和氮杂苯磺酰胺化学，完成了六环阿朴菲吲哚生物碱阿朴菲汀的高效全合成。作为第二代吲哚合成方法，我们随后开发了邻烯基硫代苯胺的自由基环化方法。通过伊波加生物碱长春花碱的全合成充分证明了该方法的合成效用。此外，通过长春多灵的实用合成实现了长春花生物碱长春碱的全合成，其中两个吲哚片段关键偶联反应的立体化学可以完全控制。除了吲哚化学，还开发了硫醇酯到酮和烯基酮的异常温和的转化反应。还描述了该方案在天然产物合成中的应用实例。
