NEW SELECTIVE REACTIONS FOR ANTI-TUMOR AGENT SYNTHESIS

该项目的长期目标是发现和开发 新的，选择性的合成反应，可以更有效地应用于 合成复杂的抗肿瘤天然产物和类似物。 在一些 在某些情况下，这些新的反应构成了酶促反应的简单模型。 在生物合成途径中运作的过程。 该提案的具体目标涉及取代基定向氧化 其中金属氧化物附着在有机基底上的反应， 作为烯烃，通过氧化剂与配体的预先配位来介导 基团存在于衬底中，如左下方示意性地示出的。 这 方法应导致更大的选择性和产品控制， 烯丙基氧化和氧化环化。 该提案包含两个 零件. 建议的第一部分介绍了研究的机制和范围 这些反应。 将制备一系列模型化合物， 在不同的反应条件下，和组合物的组成， 产品和反应速率将由适当的 光谱技术 将建立相关性之间的 观察到的选择性，以及反应条件和底物结构， 目的是建立一个可预测的理论基础。 第二部分介绍了一种全面综合的方法， 抗肿瘤剂Chapliatrin使用新的方法在一个关键的氧化 环化步骤。

The long-term goals of this project are the discovery and development of new, selective synthetic reactions which can be applied in more efficient syntheses of complex anti-tumor natural products and analogs. In some cases, these new reactions constitute simple models of the enzymic processes which operate in biosynthetic pathways. The specific aims of this proposal concern substituent-directed oxidation reactions in which the attach of a metal oxide on an organic substrate such as an alkene is mediated by prior coordination of the oxidant with a ligand group present in the substrate, as is shown schematically below left. This methodology should result in greater selectivity and product control for allylic oxidations and oxidative cyclizations. This proposal contains two parts. The first part of the proposal describes a study of the mechanism and scope of these reactions. A series of model compounds will be prepared and subjected to various reaction conditions, and the composition of the products and the rate of reaction will be monitored by appropriate spectroscopic techniques. Correlations will be established between the selectivity observed, and the reaction conditions and substrate structure, with the goal of establishing a predictive rationale. The second part describes an approach to the total synthesis of the anti-tumor agent Chapliatrin using the new methodology in a key oxidative cyclization step.