SYNTHETIC DESIGN OF FUNCTIONAL HETEROPOLYCYCLES AND THEIR APPLICATION

新的杂多环，特别是含氮体系的合成设计，为未来工业中可能应用的新材料提供了化学基础。研究结果总结如下：1.通过分子内aza-Wittig反应可以有效地得到脱氧血管紧张素酮的不对称氧化反应，从而得到喹唑啉生物碱的两个对映体Vasicin。采用分子内aza-Wittig方法合成了喹唑啉类抗肿瘤药物巴曲林和抗肿瘤抗生素DC-81。通过分子间氮杂-Wittig反应和杂环化反应合成了一种新的蝶啶类化合物。通过环加成反应设计新型多环杂环化合物。多环型硝酮的设计及其反应。镶嵌在高金刚烷骨架中的硝酮与炔烃和氮化物表现出独特的反应活性。用炔烃，他们得到了高金刚烷稠合的异恶唑啉，…更热的重排成稠合的吡咯，并与氮加成得到2，3-二氢-1，2，4-恶二唑，这提供了一条合成这种新型杂环的一般和直接的路线。含有有机氟功能的合成嵌段的设计及其应用利用自由基加成设计了α，α-二氟-羧酸和-酮等二氟亚甲基化合物。用该方法合成了α，α-二氟-γ-氨基丁酸和二氟吡啶类化合物。以三氟甲基-1，3-二酮和-烯胺为原料合成了三氟甲基化的5元和6元N杂环。小环化合物的分子设计。设计了水杨酸衍生物。方酸衍生物通过加热以及新发现的自由基开环和环合反应，转化为取代的伽马-丁烯内酯、呋喃酮和双环[3.2.0]庚烯酮。以上述环转化为关键步骤，开发了具有生物活性的天然产物(E)-巴西达林和(Z)-多氰酸酯的高效合成路线。化学修饰核苷的分子设计：胸腺嘧啶和尿嘧啶是通过在呋喃和吡喃糖链的2-和/或3-位引入氨基、溴和硝基来修饰的。2，2‘-硫胺的无氢衍生物也被用于将这些功能立体地和区域选择性地引入到嘧啶碱中。设计的杂多环的物理和生物性质。以上制备的这些新化合物的详细的物理和生物性质是未来的研究项目。较少

Synthetic designing of novel heteropolycycles, in particular N containing systems, has been carried out to provide the chemical base of new materials potentially useful in future industry. The results are summarized below.1. Design of Nitrogen Heterocycles by Using Iminophosphorane.Both enantiomers of quinazoline alkaloid, Vasicinone are prepared via asymetric oxidation of deoxyvasicinone which is efficiently obtainable by intramolecular aza-Wittig reaction. Quinazoline antitumor agent Batracylin and antitumor antibiotics DC-81 were synthesized via intramolecular aza-Wittig methodology. A new synthesis of pteridine derivatives has been developed by intermolecular aza-Wittig reaction followed by heterocyclization.2. Desgin of Novel Polycyclo-type Heterocycles by Cycloaddition. Design of Polycyclo-type Nitrones and Their Reaction. Nitrones inbeded in homoadamantane frame exhibited unique reactivity with alkynes and nitriies. With alkynes they gave homoadamantane-fused isoxazolines which … More rearranged themally to fused pyrroies and with nitriies they cycloadded to afford 2,3-dihydro-1,2,4-oxadiazoles, that provided a general and direct route to such novel heterocycles.3. Design of Synthetic Blocks containing Organofluorine Function and Their Application.Difluoromethylene compounds such as alpha, alpha-difluoro-carboxylic acids and-ketones have been designed by utilizing radical addition. alpha, alpha-Difluoro-gamma-amino butyric acid and difluoropyridones were synthesized by this method. Trifluoromethylated 5-and 6-membered N heterocycles have been synthesized using trifluoromethyl-1,3-diketone and-enamides.4. Molecular Design by Small Ring Compounds. Suaric Acid Derivatives.Squaric acid derivatives have been designed and they were converted to substituted gamma-butenolides, furanones and bicyclo [3.2.0] heptenones via thermal as well as newly found radical ring-opening followed by recyclization scheme. New efficient synthetic routes to biologically active natural products, (E) -basidalin and (Z) -multicolanate have been developed utilizing above ring-transformation as the key step.5. Molecular Design of Chemically Modified Nucleosides.Thymine and uracil were modified by introducing amino, bromo and nitro functions to the 2-and/or 3-positions of the furanose and pyranose sugar moieties. 2,2'-Anhydro derivatives of thimine was also utilized for the stereo and regio-selective introduction of these functions to the pyrimidine base.6. Physical and Biological Properties of Designed Heteropolycycles.Datailed physical and biological properties of these new compounds prepared above are future projects. Less