NEW SYNTHETIC REACTIONS FOR ACTIVE PRINCIPLES

PI对这个项目的希望是双重的。 首先，作为一种化学反应， 实验室，他的小组建议开发新的能力， 在战略和方法层面上进行综合。 提高有机合成的实力， 组装复杂的分子进行生物学检查。 在 HL2588计划的重点是一组目标，这些目标本身， 从有前景的临床前活性的角度来看， 新的生物学作用机制。 因此，选择目标 为了提供不同的合成，同时 提高了合成过程中新药先导的可能性， 用于探测结构和机制问题的基底。 大约三分之一的努力将用于 碳水化合物合成 相当多的注意力是针对 他的计划的另一部分的合成侧重于不同的化学 问题，作为探索全面综合 收集有趣和具有挑战性的天然产品目标 结构. 在这些单独的天然产物衍生项目中， 是磷脂酶抑制剂hispidospermidin（程序E）; 钩吻素（程序F），CP 225，917，其是法尼基转移酶 抑制剂（程序g），渥曼青霉素，其是细胞周期调节剂 （程序H）。 他还寻求全面综合 himastatin，也是一种细胞周期调节剂（程序I），spirotryprostatin， 在G2/M期干预细胞周期进程的试剂 相（程序J），三环冬青酮，一种天然产物， 乙酰胆碱酯酶活性（程序K）和双氢叶酸，一种蛋白质 磷酸酶抑制剂（程序L）。 讨论了相关提议 根据这些程序分类。

The PI's hopes for this project are twofold. First, as a chemistry laboratory, his group proposes to develop new capabilities in synthesis, both at the strategic and methodological levels. Enhancement of strength in organic synthesis finds ready application in assembling molecules of complexity for biological scrutiny. In the HL2588 Program the focus is on a group of targets which are, per se, of interest from the standpoint of promising pre-clinical activity or novel mechanism of biological action. Thus, the targets are selected with a view to providing differing syntheses, while at the same time raising the possibility of new drug leads in the course of synthesizing substrates for probing issues of structure and mechanism. Approximately a third of the effort will be directed toward carbohydrate synthesis. Considerable attention is to directed to the synthesis of the other part of his program focuses on diverse chemical issues as part of explorations directed to the total synthesis of a collection of interesting and challenging natural product goal structures. Among these individual natural product derived projects are the phospholipase inhibitor hispidospermidin (program E); gelsemine (program F), CP 225, 917, which is a farnesyl transferase inhibitor (program g), wortmannin, which is a cell cycle modulator (program H). He also seeks to pursue the total synthesis of himastatin, also a cell cycle modulator (program I), spirotryprostatin, an agent which intervenes in the cell cycle progression at the G2/M phase (program J), tricycloillicinone, a natural product which increases acetylcholinesterase activity (program K) and disydiolide, a protein phosphatase inhibitor (program L). The proposal was discussed according to these program classifications.