"Laboratory of Medicinal and Organic Chemistry"
Laboratory of Medicinal and Organic Chemistry Professor Tetsuaki TANAKA 06-6879-8210 firstname.lastname@example.org Associate Professor Takehiko YOSHIMITSU 06-6879-8213 email@example.com Assistant Professor Naoto KOJIMA 06-6879-8212 firstname.lastname@example.org FAX 06-6879-8214 Professor Tetsuaki TANAKA Functional organic molecules, both naturally occurring and man-made, constitute a wide range of medicines indispensable for human health. Total Synthesis of Natural Products Me Complex biological processes in the living organism are also accurately OH O controlled by their chemical interplay on a molecular level. Organic O O O chemistry, a glamorous science that deals with such molecular world, has Me HO Longimicin D OH O HO thus been pivotal to medicinal fields and has significant potential for Br N O H O H O revolutionizing the cure for obstinate diseases. N N H H HO O O O H Our research interests cover two main areas of organic chemistry, 1) N H H NCH3 H O organic synthesis of structurally complex bioactive molecules such as O Aphanorphine H anticancer and analgesic natural products, aiming at the development of Agelastatin A CP-263,114 CO2H new pharmaceuticals, 2) development of new methodology and strategy that enable efficient access to various functional molecules, ranging from Development of New Synthetic Method small synthetic building blocks to highly complex chiral compounds. O R1 R4 O R4 R2 SmI2 N N R1 HMPA 1) Organic synthesis of structurally complex bioactive molecules: our I R R 3 2 synthesis targets encompass a wide range of organic compounds isolated R 3 from natural resources, involving Annonaceous acetogenins (aniticancer & Samarium(II)-Mediated Spirocyclization immunosuppressive agent), CP-263,114 (Ras farnesyltransferase inhibitor), R H 2 R C N Ar R 2 2 agelastatin A (anticancer agent) and aphanorphine (analgestic lead), all of R X R R1 O R X 4 H O 4 R N NHAr 1 1 which are of biological significance. The purpose of our total synthesis OH Et B, air H X=O, NR Et B, air 3 R O 3 3 3 projects involves not only creating a process for retrieving a large supply of Radical C-H Transformation target compounds but also designing new functional molecules that would serve as potent medicinal leads for future drug discovery. Interdisciplinary research is also currently underway through cooperation with other research groups, pursuing bioactive substances by means of pharmacological screening of the synthesized compounds as well as gaining vital clue to understanding of their biological functions. 2) Development of synthetic methodologies and strategies: because of the advent of novel medicinal leads possessing unprecedented stereochemical and architectural complexity, discovery of efficient methodology that enables the stereoselective functionalization and transformation has become extremely important. Such methodologies, in the meantime, have faced the significant challenge with a view to saving energies necessary for the processes and avoiding environmental pollutions caused by the chemical wastes. We are pursuing novel chemical bond forming processes that will meet such requirements by employing highly reactive free radicals, organometallic species and asymmetric catalysts. Our work in this area involves SmI2-promoted single electron transfer processes, free-radical-based carbon-hydrogen (C-H) transformations and asymmetric multi-component assembly processes. Research topics 1) Total synthesis of biologically active natural products 2) Synthesis of novel natural product derivatives with antitumor activity as drug leads 3) Development of free-radical- and organometallic-based method and strategy for organic synthesis 4) Development of new methods for asymmetric synthesis Recent publications 1) T. Tanaka et al., Samarium(II)-Mediated Spirocyclization by Intramolecular Aryl Radical Addition onto an Aromatic Ring. J. Org. Chem. in press. 2) N. Kojima et al., Synthesis of Hybrid Acetogenins, α,β-Unsaturated-γ-lactone-free Nitrogen-containing Heterocyclic Analogues, and Their Cytotoxicity against Human Cancer Cell Lines. Bioorg. Med. Chem. Lett. 18, 1637, 2008. 3) T. Yoshimitsu et al., Radical Fixation of Functionalized Carbon Resources: α-sp3C-H Carbamoylation of Tertiary Amines with Aryl Isocyanates. Org. Lett. 9, 5115, 2007. 4) T. Tanaka et al., Heck-Type Cyclization of Oxime Ethers: Stereoselective Carbon-Carbon Bond Formation with Aryl Halides To Produce Heterocyclic Oximes. Angew. Chem. Int. Ed. 46, 6325, 2007. 5) T. Yoshimitsu et al., Carbon-Carbon and Carbon-Hydrogen Bond Transformations Mediated by Highly Reactive Radicals and Their Application to the Synthesis of Bioactive Compounds. J. Synth. Org. Chem. Jpn. 65, 665, 2007. 6) N. Kojima et al., Systematic Synthesis of Diastereomeric THF-ring Cores and Total Synthesis of Antitumor Annonaceous Acetogenins. Synlett (account), 993, 2006. 7) T. Yoshimitsu et al., Radical Hydroxyalkylation of C-H Bond Adjacent to Nitrogen of Tertiary Amides, Ureas, and Amines. J. Am. Chem. Soc. 127, 11610, 2005.