Development of Novel Polyyne Antibiotic Agent

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This project aims at the investigation of chemistry on conjugated polyyne compounds and the development of polyyne antibacterial agent. Advances were made on the following subjects during the period of the financial support.1) A new methodology for the synthesis of conjugated polyyne compoundsMonosilylated 1, 3, 5, 7-octatetrayne and 1, 3, 5-hexatriyne were prepared, and their lithiation, nucleophilic alkynylation, and aryl coupling were examined. A polymer film obtained by polymerization of a tetrayne showed conductivity of 10^<-3> Scm^<-1> when doped with SO_3.2) A novel activation method of acetylenic C-HAlkynylation reactions of aldehydes, acetals, and enones with 1-alkynes in the presence of SnCl_4 and Bu_3N were developed. During the studies, "carbostannylation" reaction of carbon-carbon triple bonds was discovered, which was applied to the stereoselective synthesis of tetrasubstituted enones and the direct vinylation of phenols. Both were unsolved problems in organic synthesis.3) Synthesis and biological activities of caryoynencins and related compoundsPolyyne antibiotics caryoynencins and related compounds were synthesized, and their antibacterial activities were studied. An analog lacking (CH_2)_3COOH moiety of the natural product showed potent activities against bacteria and fungi including MRSA.Another analog in which tetrayne part and diene part does not conjugated each other exhibited potent activities towards Tricophyton. It was shown that the tetrayne moiety is essential for the biological activities.