SYNTHETIC DESIGN OF FUNCTIONAL HETEROPOLYCYCLES AND THEIR APPLICATION

功能性杂多环的合成设计及其应用

• 批准号: 04403017
• 负责人: EGUCHI Shoji
• 金额: $ 22.66万
• 依托单位: Nagoya University, School Engineering
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (A)
• 财政年份: 1992
• 资助国家: 日本
• 起止时间: 1992 至 1994
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-04403017/
• 关键词: iminophosphorane; aza-Wittig reaction; nitrone; difluoromethylene group; trifluoromethyl group; squaric acid; uracil; thymine; 1,3-双極性環化付加反応; 1,2,4-オキサジアゾリン; ハロヌクレオシド; ジフルオロカルボン酸; aza-Wittig反応; ニオロオレフィン; アザーウィッチッヒ反応; ジヒドロキナゾリン; ニトリル; アジドヌ

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

新型杂多环化合物的合成设计，特别是含氮体系，为未来工业中可能有用的新材料提供了化学基础。结果总结如下：1。亚磷烷氮杂环的设计。两种喹唑啉生物碱的对映体水杨桃酮都是通过分子内aza-Wittig反应对脱氧水杨桃酮进行不对称氧化制备的。采用分子内aza-Wittig方法合成了喹唑啉类抗肿瘤药物Batracylin和抗肿瘤抗生素DC-81。采用分子间aza-Wittig反应和杂环化法制备了一种新的蝶啶衍生物。用环加成法设计新型多环型杂环。多环型氮酮的设计及其反应。含在同形金刚烷骨架中的硝基酮与炔烃和氮化物表现出独特的反应活性。他们用炔烃合成了同金刚烷-融合的异恶唑啉，这些异恶唑啉更容易重排为融合的吡啶；他们用硝基环合成了2,3-二氢-1,2,4-恶二唑，这为合成这种新型杂环提供了一条普遍而直接的途径。含有机氟功能合成块的设计及其应用。采用自由基加成法设计了α、α -二氟羧酸和酮类二氟乙烯化合物。用该方法合成了α、α -二氟-氨基丁酸和二氟吡啶酮。用三氟甲基-1,3-二酮和酰胺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。硫酸衍生物。设计了方酸衍生物，并通过热反应和新发现的自由基开环再循环，将其转化为取代-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) - basidin和(Z) -multicolanate的高效合成途径。化学修饰核苷的分子设计。胸腺嘧啶和尿嘧啶通过在呋喃糖和吡喃糖的2位和/或3位上引入氨基、溴和硝基功能进行修饰。硫胺的2,2'-无羟基衍生物也被用于立体和区域选择性地将这些功能引入嘧啶碱基。设计杂多环的物理和生物特性。这些新化合物的详细的物理和生物特性是未来的项目。少

项目成果

Masatomi Ohno: "Dihydrothiopyrane-Fused〔60〕-Fullerene from Hetero Diels-Alder Reaction with Thioacrylamide and Acyl Chloride." J.Chem.Soc.,Chem.Commun.(1995)

Masatomi Ohno：“二氢噻喃-稠合〔60〕-富勒烯与硫代丙烯酰胺和酰氯的杂狄尔斯-阿尔德反应。J.Chem.Soc.，Chem.Commun.（1995）

Katsumaro Minamoto: "Highly Efficient Synthesis of 2,2'-Anhydro-1-(3'-bromo-3'-deoxy-5'-O-trityl-β-D-arabinofuranosyl)thymine and Its Derivatives from an Unsaturated Thymine." J.Chem.Soc.,Perkin Trans.1. 2289-2296 (1994)

Katsumaro Minamoto：“从不饱和胸腺嘧啶高效合成 2,2-AnHydro-1-(3-bromo-3-deoxy-5-O-三苯甲基-β-D-阿拉伯呋喃糖基)胸腺嘧啶及其衍生物。 J.Chem.Soc.，Perkin Trans.1.2289-2296 (1994)

Shoji Eguchi: "Oxidative Rearrangement of 4-Hydroxy-2-Cyclobutenone.A New Route to Highly Substituted Euranones from Squaric Acid" Journal of Organic Chemistry. 59(17). 4707-4709 (1994)

Shoji Eguchi：“4-Hydroxy-2-Cyclobutenone 的氧化重排。从方酸中获得高度取代的 Euranones 的新路线”有机化学杂志。

Masatomi Ohno: "Ring-Transformation of 4-Acylmethy1-2-chloro-4-hydroxy-2-cyclo-butenone to γ-Acylmethylenetetronate by Thermal Rearrangement.." Tetrahedron. 50(26). 7783-7798 (1994)

Masatomi Ohno：“通过热重排将 4-酰基甲基 1-2-氯-4-羟基-2-环丁烯酮环转化为 γ-酰基亚甲基四酸酯。”Tetrahedron 50(26) (1994)。

S.Eguchi, M.Ohno: "Synthesis of C60-Fullerene Derivatives" Kikan Fura-ren. 1 (3). 99-113 (1993)

S.Eguchi，M.Ohno：“C60-富勒烯衍生物的合成”Kikan Fura-ren。