Synthetic and Medicinal Chemistry (Yasuo TAKEUCHI)

Synthetic and Medicinal Chemistry Yasuo TAKEUCHI, PhD & Hiromi NISHIOKA, PhD

Major Areas of Research

Developments of the precise synthetic chemistry and the process chemical reaction that aims at the drug development for the molecular design and the pharmaceutical synthesis, research educations concerning the relationship with the synthetic compounds and the bioactivity.

1. Fundamental study on development of new reaction and syntheses
2. Study on synthesis of natural products
3. Study on Structure-Activity Relationship (SAR)

Current Research Interests

(-)-Actinonin is an antibiotic isolated from the nutrient medium of the ray fungus Streptomyces sp. The antibacterial activity of this compound appearing by inhibiting the potent peptide deformylase (PDF) inhibitory activity becomes clear, and it is known as a typical PDF inhibitor. Moreover, (-)-actinonin was inferior to an existing medicine as a result of the anti-malaria examination, but it has an activity of the falciparum malaria. In addition, it is reported that (-)-actinonin has the antitumor activity, and is shown that human’s PDF takes part in the working mechanism. The above is based, and (-)-actinonin is paid to attention as a very attractive compound because various physiology revitalizations only as no compound that has a new working mechanism named the PDF inhibitor are shown. Acinetobactin is a siderophore that was isolated from Acinetobactor baumaunii in 1994. The bacillus of the Acinetobactor belonging widely distributed in the natural world generates the opportunistic infectious disease, and it is known especially that it is offending bacteria that spread nosocomial infection in recent years. Coumarins exist widely in the vegetable world, and those bioactivity is very various. Recently, 3′,4′-di-(O)-(-)-camphanoyl-(+)-khellactone (DCK) is well known as an anti-HIV compound, and is found showing anti-HIV activity that is higher than typical anti-HIV-1 action medicine AZT (Reverse transcriptase inhibitor). In this laboratory, the research is advanced aiming to establish a more efficient, more economical synthesis method of these compounds, and to synthesize the compound with high activity or more by using the synthesis method in addition, and to make the structure-activity relationship, and to design and to synthesize the compound with high possibility of becoming medicine or more moreover.

Selected Recent Publications

1. Synthesis of (-)-Actinonin, Inoue S., Nishioka H., Abe H., Harayama T., Takeuchi Y., Synthesis, (11), 1705-1710 (2011).
2. Synthesis and Anti-human Immunodeficiency Virus Activity of the Skeleton Isomers of 3′,4′-Di-(O)-(-)-camphanoyl-(+)-khellactone, Nishioka H., Uesugi K., Ueda N., Kondo Y., Tsuji M., Abe H., Harayama T., Hamasaki T., Baba M., Takeuchi Y., Chem. Pharm. Bull., 59(8), 1075-1076 (2011).
3. Synthesis of Zanthoxyline and Related Compounds: Revisin of the Reported Structure, Abe H., Kobayashi M., Y., Takeuchi T. Harayama., Heterocycles, 80(2), 873-877 (2010).
4. Novel indoline-based acyl-CoA: cholesterol acyltransferase inhibitor: Effects of introducing a methanesulfonamide group on physicochemical properties and biological activities, Shoji Y., Takahashi K., Ohta M., Kasai M., Kunishiro K., Kanda M., Yogai S., Takeuchi Y., Shirahase H., Bioorg. Med. Chem., 17(16), 6020-6031 (2009).
5. Preparation of 5H,7H-Dibenz[c,e]oxepin-5-one Derivative through Reconstruction of the Lactone Ring, Abe H., Arai M., Takeuchi Y., Harayama .T., Heterocycles, 77, 1416-1416 (2009).
6. Synthesis of Highly Oxygenated Biphenyl Derivative in an Optically Active Form through Palladium-Mediated Intramolecular Biaryl Coupling Reaction, Abe H., Arai M., Nishioka K., Kida T., Shioe K., Takeuchi Y., Harayama T., Heterocycles, 76, 291-303 (2008).