Synthetic/Mechanistic Investigations of Antitumor Agents

描述：(申请人提供)本建议书描述延续 一项研究计划，涉及行动研究的综合和模式 结构复杂的天然产物具有独特的抗肿瘤作用 活动。描述了三个主要项目。第一个项目涉及 大环内酯类抗肿瘤药物凋亡素的合成及生物学研究 诱导转化的细胞经历程序性细胞死亡。我们计划 继续开发凋亡素和结构蛋白的简明合成方法 旨在探测凋亡素细胞靶点的类似物，这是一种相互作用 被认为是独一无二的细胞死亡的原因。第二个项目是 旨在合成结构复杂的天然产物 酪氨酸激酶和肿瘤细胞的特异性抑制剂--组米素B 转型。第三个项目旨在开发一种 2-脱氧低聚糖快速组装的通用方法 天然抗肿瘤抗生素的结构特征。总体而言，这个计划是 预计将对化学、生物和生物领域产生重大影响 医药。

DESCRIPTION: (provided by applicant) This proposal describes the continuation of a research program involving the synthesis and mode of action studies of structurally complex natural products that have demonstrated unique antitumor activity. Three major projects are described. The first project involves synthetic and biological studies on apoptolidin a macrolide antitumor agent that induces transformed cells to undergo programmed cell death. We plan to continue development of a concise synthesis of apoptolidin and structural analogs designed to probe the cellular target of apoptolidin, an interaction presumed responsible for the unique onset of cell death. A second project is directed toward the synthesis of the structurally complex natural product hibarimicin B, a specific inhibitor of tyrosine kinase and oncogenic cell transformation. A third project is directed towards the development of a general method for the rapid assembly of 2-deoxy oligosaccharides, a frequent structural feature of natural antitumor antibiotics. Overall, this program is expected to have a significant impact on the areas of chemistry, biology and medicine.