Laboratory of Medicinal and Organic Chemistry - 大阪大学 · Laboratory of Medicinal and Organic...
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Laboratory of Medicinal and Organic Chemistry Professor Tetsuaki TANAKA 06-6879-8210 t-tanaka@ phs.osaka-u.ac.jp Associate Professor Takehiko YOSHIMITSU 06-6879-8213 yoshimit@ phs.osaka-u.ac.jp Assistant Professor Naoto KOJIMA 06-6879-8212 kojima@ phs.osaka-u.ac.jp 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. Complex biological processes in the living organism are also accurately controlled by their chemical interplay on a molecular level. Organic chemistry, a glamorous science that deals with such molecular world, has thus been pivotal to medicinal fields and has significant potential for revolutionizing the cure for obstinate diseases. Our research interests cover two main areas of organic chemistry, 1) organic synthesis of structurally complex bioactive molecules such as anticancer and analgesic natural products, aiming at the development of new pharmaceuticals, 2) development of new methodology and strategy that enable efficient access to various functional molecules, ranging from small synthetic building blocks to highly complex chiral compounds. 1) Organic synthesis of structurally complex bioactive molecules: our synthesis targets encompass a wide range of organic compounds isolated from natural resources, involving Annonaceous acetogenins (aniticancer & immunosuppressive agent), CP-263,114 (Ras farnesyltransferase inhibitor), agelastatin A (anticancer agent) and aphanorphine (analgestic lead), all of which are of biological significance. The purpose of our total synthesis projects involves not only creating a process for retrieving a large supply of 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 SmI 2 -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, , -Unsaturated- -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: -sp 3 C-H Carbamoylation of Tertiary Amines wit h 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 an d 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. Aphanorphine Et 3 B, air Et 3 B, air X=O, NR 3 Total Synthesis of Natural Products Development of New Synthetic Method Samarium(II)-Mediated Spirocyclization SmI 2 HMPA Longimicin D Radical C-H Transformation H CP-263,114 Agelastatin A
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Transcript of Laboratory of Medicinal and Organic Chemistry - 大阪大学 · Laboratory of Medicinal and Organic...
Laboratory of Medicinal and Organic Chemistry
Professor Tetsuaki TANAKA 06-6879-8210 t-tanaka@ phs.osaka-u.ac.jp Associate Professor Takehiko YOSHIMITSU 06-6879-8213 yoshimit@ phs.osaka-u.ac.jp Assistant Professor Naoto KOJIMA 06-6879-8212 kojima@ phs.osaka-u.ac.jp 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. Complex biological processes in the living organism are also accurately controlled by their chemical interplay on a molecular level. Organic chemistry, a glamorous science that deals with such molecular world, has thus been pivotal to medicinal fields and has significant potential for revolutionizing the cure for obstinate diseases.
Our research interests cover two main areas of organic chemistry, 1) organic synthesis of structurally complex bioactive molecules such as anticancer and analgesic natural products, aiming at the development of new pharmaceuticals, 2) development of new methodology and strategy that enable efficient access to various functional molecules, ranging from small synthetic building blocks to highly complex chiral compounds.
1) Organic synthesis of structurally complex bioactive molecules: our synthesis targets encompass a wide range of organic compounds isolated from natural resources, involving Annonaceous acetogenins (aniticancer & immunosuppressive agent), CP-263,114 (Ras farnesyltransferase inhibitor), agelastatin A (anticancer agent) and aphanorphine (analgestic lead), all of which are of biological significance. The purpose of our total synthesis projects involves not only creating a process for retrieving a large supply of 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, , -Unsaturated- -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: -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.
Aphanorphine
Et3B, airEt3B, airX=O, NR3
Total Synthesis of Natural Products
Development of New Synthetic Method
Samarium(II)-Mediated Spirocyclization
SmI2HMPA
Longimicin D
Radical C-H Transformation
H
CP-263,114Agelastatin A
Yoshimitsu
四角形
Yoshimitsu
テキストボックス
1) N. Kojima et al., Asymmetric Alkynylation of Aldehydes with Propiolates without High Reagent Loading and Any Additives. Org Biomol Chem, in press. 2) T. Yoshimitsu et al., Total Synthesis of (±)-Kainic Acid: A Photochemical C-H Carbamoylation Approach. Org Lett, 13, 2674, 2011. 3) T. Yoshimitsu et al., Asymmetric Total Synthesis of (+)-Danicalipin A. Org Lett, 13, 908, 2011. 4) N. Kojima et al., Convergent Synthesis of Fluorescence-Labeled Probes of Annonaceous Acetogenins and Visualization of Their Cell Distribution. Bioorg Med. Chem., 18, 8630, 2010. 5) T. Yoshimitsu et al., Asymmetric Total Synthesis of (+)-Hexachlorosulfolipid, a Cytotoxin Isolated from Adriatic Mussels. J Org Chem, 75, 5425, 2010. 6) N. Kojima et al., One-Pot, Three-Component Synthesis of Chiral 4-Alkylidene-2-oxazolidinones. Synlett, 3171, 2009. 7) T. Yoshimitsu et al., Studies on the Asymmetric Total Synthesis of Clavilactone D via 'Lariat' Cyclization Strategy. Synthesis, 2963, 2009. 8) T. Yoshimitsu et al., Total Synthesis of beta-Catenin Inhibitor, (-)-Agelastatin A: A Second-Generation Approach Based on Radical Aminobromination. Org Lett, 11, 3402, 2009. 9) N. Kojima et al., Convergent Synthesis of Fluorescence Labeled Solamin. Heterocycles, 79, 387, 2009. 10) T. Yoshimitsu et al., Enantiocontrolled synthesis of polychlorinated hydrocarbon motifs: a nucleophilic multiple chlorination process revisited. J Org Chem, 74, 696, 2009. 11) T. Yoshimitsu et al., Synthesis of Chaetomellic Anhydride A, a Potent Inhibitor of Ras Protein Farnesyltransferase. Heterocycles, 77, 179, 2009.
