Synthetic/Mechanistic Investigations of Antitumor Agents

描述：（由申请人提供）本提案描述了 一项研究计划，涉及的综合和行动方式的研究， 结构复杂的天然产物，已证明具有独特的抗肿瘤作用， 活动介绍了三个主要项目。第一个项目涉及 大环内酯类抗肿瘤药雷公藤甲素合成及生物活性研究 诱导转化细胞进行程序性细胞死亡。我们计划 继续开发了雷公藤甲素的简明合成方法和结构 设计用于探测雷公藤甲素的细胞靶点的类似物， 被认为是导致细胞死亡的唯一原因。第二个项目是 直接合成结构复杂的天然产物， 酪氨酸激酶特异性抑制剂--hibarimicin B与肿瘤细胞 转型第三个项目旨在制定一个 快速组装2-脱氧低聚糖的通用方法， 天然抗肿瘤抗生素结构特征总的来说，该计划是 预计将对化学，生物学和生物学领域产生重大影响。 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.