Developement of Novel Synthetic Blocks with Unique Structure and Their Application to Molecular Design of Bioactive Molecules

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In this project, some selected compounds with unique ring structures such as adamantane, fullerene, and squaric acid after appropriate functionalization have been shown to be useful novel synthetic blocks for molecular design of bioactive molecules including some natural products. The outline of he research results are summarized below :(1) Developement of synthetic methods of functionalized carbo- and heteropolycycles : Homoadmant 3-enes conjugatively stabilized by 4-phenyl or -methoxycarbonyl group have been shown to be useful as novel building blocks. N-(2-Substituted phenyl) iminophosphosranes have been applied successfully to total synthesis of bioactive natural products such as Vascinone and Benzomalvin A etc. N-(2-Heteroaryl) iminophosphoranes have been developed as useful building blocks for synthesis of pteridinones and their analogues. New efficient routes to 5,6-dihydropyrrolo [2,1-a] isoquinolines have been developed via [3+2] cycloaddition of 3,4-dihydroisoquinoline N-oxid … More es with alkynes and allenes, followed by rearrangements.(2) Molecular design of heterocycle-containing [60] fullerenes by cycloaddition : C60 has been shown to be reactive enough even with 1,3-dienes having elecvtron-withdrawing groups to afford functionalyzed fullerocyclohexenes. Heterocycle-containing fullerenes have desinged and synthesized via [2+4] cycloaddition with various hetero dienes, heterocyclic quinodimethanes, and heterocycles. and via [2+3] cycloadditions with silylnitoronate, nitroalaknes, and beta-dicarbonyl compounds. Furan and oxazole-linked fullerenes have been oxygenated readily by self-sensitized photooxygenation as one of unique behaviors of these heterocycles.(3) New potentials of squaric acid as C4 synthon : We have developed a new method for functionalization of squaric acid by the Lewis acid catalyzed elecrophilic addition to unsaturated organosilanes via 1,2-and/or 1,4-modes. Thus obtained derivatives could be converted to functionalyzed bicyclo [3.2.0]-heptanes and furanones, which have been utilized to synthesize tricyles such as triquinane skeletons and (E)-Basidalin. We have found a new ring exapansion via 0-radical-induced ring opening, followed by a novel 5-endo trig cyclization to provide alkylidenefuranones which were utilized to synthesis of antibiotic (Z)-Multicolanate.(4) Developement of novel fluorine-containing synthetic blocks : A general synthetic method for alpha, alpha-difluoromethylenealkane carboxylic acid and -ester has been developed via radical addition to difluorodichloroalkenes, followed by solvolysis. Starting from trifluoromethylaceate, synthestic routes to fused nitrogen heterocycles including alkaloids carrying a CF_3 group on the bridgehead position have been developed via radical-and/or iminium cyclizations. beta-Trifluoromethylvinylsulfonyl compounds prepared from trifluoroacetate have been shown to be new synthetic blocks useful for regio-, stereo-, and enantioselective synthesis of trifluoromethylated organic compounds. Less