Applied Natural Product Chemistry

Bioscience Based on Synthetic Organic Chemistry

Staffs

	Professor：Hiromasa KIYOTA, Ph. D. E-mail： kiyota＠（@cc.okayama-u.ac.jp） Synthetic Organic Chemistry, Natural Product Chemistry
	Associate Professor：Minoru IZUMI, Ph. D. E-mail： mizumi＠（@cc.okayama-u.ac.jp) Synthetic Organic Chemistry, Glycoscience

Research Topics

Synthetic Studies of Biologically Active Organic Compounds and their Application to Agrochemicals and Medicines
Total Synthesis of Biologically Active Natural Products
Biological functions are always controlled and regulated by seemingly invisible small molecules. Human society has developed along with the exploitation of small molecules (as they are, or as modified compounds) to control biological phenomena. This includes increasing crop production with agrochemicals, exterminating pests using pesticides, treating illnesses with medicines and so on. The primary models have always been discovered in nature and modified by chemists. This is the “synthetic organic chemistry of natural products" which we study. More specifically, structural modification of a biologically active natural compound to increase specific activity and to decrease undesired toxicity could lead to the development of a medicine. In addition, preparation of a natural compound, which is not easily isolated in large quantity, for the purpose of biological examination, could clarify an unexplained phenomenon. We have achieved the synthesis of a variety of compounds as follows, and continue working on these challenges (see also the lab homepage for more detail).

Synthetic Studies of Natural Products with Strong Biological Activity and/or Strange Structure
(1) Enacyloxins, a series of antibiotics isolated from Frateuria sp. W-315, are paid attention to due to their unique polyene-polyol structures and selective antibiotic activity (by inhibiting protein synthesis). We have developed a new dianion-type Cu-mediated coupling reaction and aim at total synthesis.
(2) Maoecrystal V, isolated from a Chinese medicinal herb, shows strong anti-tumor activity comparable to cis-platin. We engage in synthetic studies using highly stereoselective Diels-Alder reaction as the key step.
(3) Development of novel anti-influenza agents: The emergence of resistant influenza strains has posed a serious challenge to the use of conventional influenza drugs (sialidase inhibitors) such as Tamiflu, Relenza etc. Difluorosialic acid functions via a novel mechanism by forming a covalent bond with the enzyme and closely resembles the natural substrate; therefore it is expected to be a promising anti-influenza agent.

Publications

・ Influenza Neuraminidase Operates via a Nucleophilic Mechanism and can Be Tageted by Covalent Inhibitors, C. J. Vavricka et al., Nat. Commun.., 4, 1491 (2013).
・ Facile Synthesis of the Cyclohexane Fragment of Enacyloxins, a Series of Antibiotics Isolated from Frateruria sp. W-315, A. Saito et al., Biosci. Biotechnol. Biochem.., 78(5), 766-769 (2014).
・ Novel Phosphorylation of Aldrin-trans-diol by Dieldrin-degrading Fungus Mucor racemosus strain DDF, K. Yamazaki et al., Int. Biodet. Biodeg.., 92, 36-40 (2014).
・ Rosen, D., Lewis, A. M., Mizote, A., Thomas, J. M., Aley, P. K., Vasudevan, S. R., Parkesh, R., Galione, A., Izumi, M., Ganesan, A., Churchill G. C.: Analogues of the nicotinic acid adenine dinucleotide phosphate (NAADP) antagonist Ned-19 indicate two binding sites on the NAADP receptor. J. Biol. Chem., 284, 34930-34934 (2009)
・ Naylor, n., Arredouani, A., Vasudevan, S. R., Lewis, A. M., Parkesh, R., Mizote, A., Rosen, D., Thomas, J. M., Izumi, M., Ganesan, A., Galione, A., Churchill, G. C.: Identification of a Chemical Probe for NAADP by Virtual Screening. Nature Chemical Biology, 4, 220-226 (2009).