Takayuki Tsunoda’s research while affiliated with Hokkaido University and other places

During the course of our studies toward the total synthesis of nigricanoside A dimethyl ester, a prototype method for the connection of the left- and right-half segments at the C9′–C10′ double bond was developed using a model system. The method was based on a simple three-step process including: (i) a nitroaldol reaction, (ii) chlorination or thionocarbonylation, and (iii) radical elimination.

A method for the stereoselective construction of the C8′–O–C6″ ether of nigricanoside-A, an antimitotic natural product from the green alga Avrainvillea nigricans, has been developed based on chirality-transferring Ireland–Claisen rearrangement. The method was successfully applied to the synthesis of simple models for the C20 lipid chain/galactosyl glycerol segment of the natural product.

We isolated a novel 2',3'-dihydoroxy-p-terphenyl derivatives 2',3'-dihydoroxy-p-terphenyl derivative, thelephantin O (TO), which has cancer-selective cytotoxicity. In this study, we investigated the underlying basis of the cytotoxicity of 2',3'-dihydroxy-p-terphenyl compounds in view of their ability to chelate metal ions. FeCl(2) significantly reduced TO-induced cytotoxicity, while several other salts of transition metals and alkaline-earth metals did not. A structure-activity relationship study using newly synthesized p-terphenyl derivatives revealed that ortho-dihydroxy substitution of the central benzene ring was necessary for both the cytotoxicity and Fe(2+) chelation of the compounds. Real-time PCR array and cell cycle analysis revealed that TO-induced cytotoxicity was attributed to cell cycle arrest at the G1 phase via well-known cell cycle-mediated genes. The TO-induced changes in the cell cycle and gene expression were completely reversed by the addition of FeCl(2). Thus, we conclude that Fe(2+) chelation occurs upstream in the pivotal pathway of 2',3'-dihydroxy-p-terphenyl-induced inhibition of cancer cell proliferation.