ORGANOTITANIUM REAGENTS IN SYNTHESIS

该提案旨在探索一些基于有机钛的新化学

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.