ORGANOTITANIUM REAGENTS IN SYNTHESIS

合成中的有机钛试剂

• 批准号: 2183558
• 负责人: NICOS A PETASIS
• 金额: $ 13.09万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-07-01 至 1995-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2183558
• 关键词: alkenes; aluminum; antifungal agents; antineoplastic antibiotics; antiviral agents; chemical bond; cyclization; drug design /synthesis /production; enol; esters; inhibitor /antagonist; lactones; lignans; molecular rearrangement; nucleoside analog; nucleosides; organometallic compounds; platelet activating factor; titanium

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.

该提案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，钛非常 丰富，通常无毒且相对便宜 不寻常的化学多样性和反应性。 任何新的合成反应 因此，基于钛的材料可能具有广泛的适用性和范围。 一些有趣的机械和合成可能性与一系列 正在提议通用类型CP2TiRR'的二茂钛衍生物。 许多涉及这种化学的合成策略正在研究中 考虑将与探索性研究并行研究。 利用该方法合成一类新的潜在 PAF 拮抗剂 提出了技术。 这类化合物引起了人们的极大兴趣 与治疗炎症、哮喘和其他几种疾病的关系 疾病。 具有重要生物学意义的一类化合物的简明合成方法 正在提议使用碳环核苷 抗真菌和抗病毒药物阿里斯特霉素和的全合成 卡巴丁。 该策略的一部分是一种罕见的铝介导的 [1,3]-σ重排，将进一步研究。 抗肿瘤酮糖核苷 psicofuranine 的新合成方法是 还提出了一些新的建议，同时建议采用类似的技术 核苷类似物的类型，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 具有治疗癌症、艾滋病和其他病毒性疾病的潜力。 最终，该项目将增强有机合成作为 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。