ORGANOTITANIUM REAGENTS IN SYNTHESIS

这项提议旨在探索一些基于有机钛的新化学 化合物，并将所得技术应用于合成 生物活性化合物 与许多其他元素不同，钛是相当 丰富，通常无毒且相对便宜， 异常的化学多样性和反应性。 任何新的合成反应 因此，基于钛的材料可以具有广泛的适用性和范围。 一些有趣的机械和合成的可能性， 提出了一般类型CP 2TiRR ′的二茂钛衍生物。 许多涉及这种化学的合成策略正在被 考虑将与探索性研究平行研究。 利用此合成一类新的潜在PAF拮抗剂， 技术提出。 这种类型的化合物是非常感兴趣的， 与炎症、哮喘和其他几种疾病治疗的关系 疾病 一个简洁的合成方法，生物学上重要的类 碳环核苷被提出，这将被用于 抗真菌和抗病毒剂阿替霉素和 卡波丁 这种策略的一部分是一种罕见的铝介导的 [1，3]-σ迁移重排，这将进一步研究。 本发明涉及一种抗肿瘤的酮糖核苷psicofuranine的新合成方法， 还提出，而类似的技术建议，为几个新的 类型的核苷类似物，可用于开发 新的反义核苷酸。 这些修饰的核苷酸具有很大的 治疗癌症、艾滋病和其他病毒性疾病的潜力。 最终，这个项目将提高有机合成的能力， 生物医学研究的工具，并将提供各种分子， 进一步的生物学研究。

This proposal seeks to explore some new chemistry based on organotitanium compounds and to apply the resulting technology to the synthesis of bioactive compounds. Unlike many other elements, titanium is quite abundant, generally nontoxic and relatively inexpensive while it exhibits unusual chemical diversity and reactivity. Any new synthetic reactions based on titanium, therefore, may have wide applicability and scope. Some intriguing mechanistic and synthetic possibilities with a series of titanocene derivatives of the general type CP2TiRR', are being proposed. A number of synthetic strategies involving this chemistry are being considered which will be studied in parallel to the exploratory studies. The synthesis of a new class of potential PAF antagonists utilizing this technology is proposed. This type of compounds are of great interest in relationship to the treatment of inflammation, asthma and several other diseases. A concise synthetic approach to the biologically important class of carbocyclic nucleosides is being proposed, which will be employed to the total synthesis of the antifungal and antiviral agents aristeromycin and carbodine. Part of this strategy is a rare aluminum-mediated [1,3]-sigmatropic rearrangement, which will be studied further. A novel synthesis of the antitumor ketose nucleoside psicofuranine is also proposed, while similar technology is suggested for several new types of nucleoside analogues, which could be used in the development of novel antisense nucleotides. These modified nucleotides have a great potential for the treatment of cancer, AIDS and other viral diseases. Eventually, this project will enhance the power of organic synthesis as a tool in biomedical research and will make available various molecules for further biological studies.