ORGANOTITANIUM REAGENTS IN SYNTHESIS

这一建议旨在探索一些基于有机钛的新化学。 并将所产生的技术应用于合成 生物活性化合物。与许多其他元素不同的是，钛 丰富的，一般无毒的，相对便宜的，虽然它展示 不同寻常的化学多样性和反应性。任何新的合成反应 因此，基于钛的可能具有广泛的适用性和范围。 一些耐人寻味的机械和综合可能性，通过一系列 正在提出通用型CP2TiRR‘的钛茂衍生物。 一些涉及这种化学的合成策略正在被 将在探索性研究的同时进行研究。 利用该化合物合成一类新型潜在的PAF拮抗剂 技术的提出。这种类型的化合物对 与炎症、哮喘和其他几种疾病的治疗关系 疾病。 一种简明的综合方法来处理生物学上重要的一类 碳环核苷正在被提出，它将被用于 抗真菌和抗病毒药物阿司匹林和阿司匹林的全合成 卡布丁。这一策略的一部分是罕见的铝调解 [1，3]-Sigmatrotic重排，将进一步研究。 一种新的抗癌酮糖核苷的合成方法 还建议，而类似的技术被建议用于几个新的 核苷类似物的类型，可用于开发 新型反义核苷酸。这些修饰的核苷酸具有很好的 治疗癌症、艾滋病和其他病毒性疾病的潜力。 最终，这个项目将增强有机合成作为一种 生物医学研究的工具，并将提供各种分子用于 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.