NEW METHODOLOGY FOR THE SYNTHESIS OF ANTI TUMOR AGENTS

这项建议是针对发展新的 构建自然生成物质的方法 具有重要的生物活性。这些研究的目标是 我们在这里提出的并不是复杂有机化合物的全合成 分子本身，而是新策略的发展 合成化学的应用将超越 建造特定类别的天然产品。我们有 发展了分子内(2+2)光环加成方案， 分子内二恶烯酮的光环加成反应，并具有 证明了它在化合物的合成中的有效性 不能以其他方式准备。我们建议在此应用这一点 控制绝对立体化学的方法学 光化学环化反应，并对天然产物进行制备 具有重要细胞毒性的化合物。我们 在此也用不同的方法描述我们的初步结果 生色团，一种葡萄糖酰胺，它会导致 含氮环系。关于语言共性的研究 该工艺及其在抗肿瘤合成中的应用 本文提出了生物碱类化合物。 通过以上概述的研究，我们希望开发新的 立体化学控制形成的方法学 碳-碳键。使用现成的手性助剂， 分子内二恶烯酮光环加成反应提供 实现绝对控制的巨大希望 立体化学--现代合成有机的重要目标 化学反应。我们为合成概述的策略 利用分子内(2+2)光环加成反应合成天然产物 二恶烯酮和乙烯基酰胺类化合物在 Diels-Alder反应、阳离子多烯环化和芳烃- 烯烃环加成反应。不止一个碳-碳键和 大量的立体化学信息是在一个单一的 综合作业。碳素骨架的结构 紫杉烷和硬脂烷二萜、紫杉素、中膜和 这项提案中概述的长春花碱证明了 这一方法在合成方面有相当大的潜力。

This proposal is directed towards the development of new approaches to the construction of naturally occurring substances with important biological activity. The goal of the studies that we propose herein is not the total synthesis of complex organic molecules per se, but rather the development of new strategies in synthetic chemistry which will have applications beyond the construction of a particular class of natural products. We have developed an intramolecular (2+2) photocycloaddition protocol, the intramolecular dioxolenone photocycloaddition, and have demonstrated its utility in the synthesis of compounds which cannot be otherwise prepared. We propose herein to apply this methodology to the control of absolute stereochemistry in the photochemical cyclization, and to the preparation of naturally occurring compounds with important cytotoxic properties. We also describe herein our preliminary results with a different chromophore, a vinylogous amide, which leads to the formation of nitrogen-containing ring systems. A study of the generality of this process, and its application to the synthesis of antitumor alkaloids is proposed herein. Through the studies outlined above, we hope to develop new methodology for the stereochemically-controlled formation of carbon-carbon bonds. Using readily available chiral auxiliaries, the intramolecular dioxolenone photocycloaddition offers considerable promise for achieving absolute control of stereochemistry, an important goal in modern synthetic organic chemistry. The strategy that we have outlined for the synthesis of natural products using intramolecular (2+2) photocycloadditions of dioxolenones and vinylogous amides has counterparts in the Diels-Alder reaction, cationic polyene cyclization, and arene- olefin cycloaddition. More than one carbon-carbon bond and considerable stereochemical information is generated in a single synthetic operation. The constructions of the carbon skeleta of the ingenane and clerodane diterpenes, taxusin, mesembrine, and the vinca alkaloids outlined in this proposal attest to the considerable potential for this methodology in synthesis.