ペプチド研究センター長
特定教授
現在の研究概要と履歴
＜＜ペプチド創薬へのゲームチェンジ＞＞
以前の研究の経緯
最善、最適の触媒を創出することは、有機化学者に課せられた最重要課題である。小さなプロトン（水素カチオン）は、無害で、有効な触媒であるが、その触媒反応を思い通りに制御することは難しい。酵素は見事にプロトンを使いこなしているが、同じことをフラスコ内で再現することはできない。私たちはプロトンに替わる触媒を探索し、いち早く1980年代初頭にC2型キラル・ルイス酸触媒が巨大分子量の酵素分子の機能を真似ながらも、その仕組みを単純化したC2対称軸を持つキラル・ルイス酸触媒を提案・実現した。この触媒は優れた不斉合成の機能を発現し、その後続々と内外から発表された同様の不斉分子性酸触媒の源流となった。本概念はその信頼性と有用性から、現在では不斉炭素ー炭素結合を作る有機合成に必須の手法として広く定着している。すなわち、我々は、キラル・ルイス酸触媒の研究を世界に先駆けて提案、その有用性を実証し、不斉炭素骨格生成に有効な「分子性酸触媒」という新分野を拓いた。
最近では、さらに高選択性を得ることのできる、ルイス酸とブレンステッド酸を組み合わせた複合型酸触媒、ルイス酸の金属中心がキラルとなるシス・ベータ型金属触媒、2つの螺旋を組み合わせたシス・アルファ型鉄触媒の創成に成功している。これらの触媒は炭素ー炭素結合の不斉合成に留まらず、酸素ー炭素、窒素ー炭素等を含む、第二世代の分子性酸触媒の創成に繋がっている。さらに、上記の概念を用いる不斉酸化反応を数々提案し、その有効性も同時に実証した。一方では、金属に替わる毒性のまったくない強力なスーパー・ブレンステッド酸触媒を開発、それを駆使した3次元分子の1工程合成に成功し、多くの労力と、莫大なエネルギー・資源を消費する従来型多段階の化学合成から脱却、クリーンで省資源型のカスケード型合成法に成功した。
開発した触媒や反応剤は工業的にも日常的に用いられている。例えば、アルミニウム反応剤はプロスタグランディン合成に、アミド化ホウ素触媒は、いくつかの医薬品プロセス合成に、バナジウム触媒は工業的規模での不斉酸化に用いられている。
私たちの有機合成への貢献は、基本的で、オリジナルな「分子性酸触媒」設計の概念を世界に先駆けて提唱、その有効性を内外に実証した。提案した「分子性酸触媒」の諸概念は全て世界初の提案で、その独創性・有効性は高い。
最近のトピックス：
アミノ酸から体内で合成されるペプチドやタンパクは人体の最も重要な機能物質である。これを、縦横に用いることで、人間は体内の働きを精妙に調整している。一世紀昔、エミールフィッシャーが簡単なペプチド合成に成功し、半世紀昔、メリフィールドが直鎖ペプチドの合成にも成功した。その後今日に至るまで、様々な改良が進んできたが、未だに50個のアミノ酸が繋がったペプチド1グラムが1億円と人の手に届かない価格である。一方、ペプチドは生体に優しく、副作用がなく、人や、動物や、植物に微量で驚くほど効果的に作用する。今日、生体内の様々なペプチドが単離、構造決定されて、毎週のように科学雑誌を賑わせている。しかし、それらのペプチドが実際に医薬品として市場に出ることはほとんど無い。価格が高すぎ、微量にしか合成できないからである。
山本の開発した革新的なペプチド合成法はまさに一世紀から半世紀にかけての、ペプチド合成の長い眠りを覚ますものであり、一気に様々な課題を解決した。本法によって、ペプチドの価格は1/1000から1/10000にまでになる。上で述べたグラム一億円がグラム一万円になるのであり、このレベルであれば、医薬品としても、十分に対応可能な価格レベルである。
もちろん、そのためには従来の手法とは全く異なるアプローチが要求された。有機合成にはこれまで、「反応剤支配」の反応が主流であった。山本博士は長年のルイス酸触媒の研究から、新しい「基質支配」の反応こそ新しい有機化学を創ることができると考え、ルイス酸を基盤とする基質支配の反応を実証する様々な成果を発表してきたが、実は、この基質支配の反応のコンセプトこそ、新しいペプチド合成の基盤となった。具体的には、反応剤支配のカルボン酸活性化法ではペプチド合成においてラセミ化を完全に防ぐことができず、それが高価格の原因の一つであったが、基質支配の反応に切り替えることでラセミ化は起こらず、この一世紀の難問が解決した。さらには、複数のペプチド鎖同士を自在に連結する手法の開発である。これによって、長鎖ペプチドの合成が簡略化され、工程数が激減する。もう一つの改革はこれまでのペプチド合成では避けることができなかった保護基を全く使わない合成方法を開発したことであり、これで工程数が1/3に短縮している。いずれも基質支配の反応の成果である。こうした様々な革新・改良を重ねることで飛躍的な低価格化に成功し、高純度なペプチドを人類に提供できるようになった。このペプチド合成は今後の200兆円の市場と言われる創薬の主役をペプチドが担うことになるばかりでなく、化粧品、サプリメント、マテリアル等、様々な分野に変換と革命をもたらす。
略歴
| 昭和42年3月 | 京都大学工学部工業化学科卒 |
| 昭和46年3月 | 米国ハーバード大学大学院博士課程修了 Ph. D. |
職歴
| 昭和46年6月 | 東レ株式会社基礎研究所研究員 |
| 昭和47年4月 | 京都大学工学部助手 |
| 昭和51年10月 | 同大学講師 |
| 昭和52年9月 | ハワイ大学淮教授 |
| 昭和55年4月 | 名古屋大学工学部講座担当助教授 |
| 昭和58年4月 | 同大学教授（平成15年 名誉教授；平成30年 特別教授） |
| 平成14年7月 | シカゴ大学化学教室教授（平成24年7月 名誉教授） |
| 平成23年7月 | 中部大学教授 分子性触媒研究センター長 |
学術論文は＞560報（引用3.7万回）、 総説は＞140報、著書＞10冊にあげられ、hインデックスは >98（雑誌のみ>115）。受賞および受章：IBM科学賞1988 服部報公賞1991 中日文化賞1992プレログメダル1993 メルクシューハルト賞1994 日本化学会賞1995 東レ科学技術賞1997 マックス・ティシュラー賞1998 フランス化学会賞2002 テトラへドロンチェアー2002 紫綬褒章2002 分子不斉賞2003 AAAS フェロー2003 山田賞2004 テトラへドロン賞2006 カールチーグラー賞2006 学士院賞2007 フンボルト賞2007 日本化学会名誉会員2008 アメリカ化学会創造賞2009 有機合成化学特別賞2009 アメリカ学士院会員2011 野依賞2011 藤原賞2012 ロジャー・アダムス賞2017 瑞宝中綬章2018 文化功労者2018 名古屋大学特別教授
Research Accomplishment of Professor Hisashi Yamamoto
Most molecules bear several functional groups,and these groups are mildly basic. When a Lewis acidic reactant approaches a functional group, it exerts influence and the molecule is activated. Dr. Yamamoto used this mechanism in founding designer Lewis acid catalysis, and developed selective construction methods for molecular frameworks. Hence, Lewis acid catalysis is widely utilized as the most important catalyst in current organic synthesis. The origin of this chemistry lies in Yamamoto’s research. For example, after he designed and developed the world’s first chiral Lewis acid catalyst in the 1980s it became the prototype for asymmetric Lewis acid catalysis. Since then, he has achieved numerous asymmetric catalyses based on the Lewis acid concept. These are methods that, based on Lewis acids activating specific functional groups, flexibly construct molecular frameworks. Today, the ability to synthesize complex molecules has been greatly supported by his acid catalysis.
Recently, by activating amino acids with a Lewis acid catalyst, he accomplished new peptide syntheses with unprecedented efficiency. Classically most synthetic research toward peptides is focused on the activation of carboxylic acids using solid-state procedures. Unfortunately, this leads to undesired racemization and missing amino acids during the linear process. The necessary purification at the later stages of synthesis requires complicated procedures that make the produced peptides quite expensive. The cost of nearly one million dollars for one gram of a pure 50 residue oligopeptide is a rather startling price tag. Meanwhile, the recent rapid progress of biological research has lead to discovery of new biologically active peptides almost every week. However, because of the high cost of peptide synthesis, these interesting molecules remain unavailable in the market. Dr. Yamamoto’s new peptide synthesis based on Lewis acid concepts reduces the cost of synthetic peptides to less than 1/10000 of the current level. In fact, his peptide synthesis solves the problem of racemization almost completely. For example, phenylglycine, known as the most difficult amino acid for non-racemization coupling, gave >99.8% pure peptide using his peptide synthesis.
Furthermore, his new method provides a new peptide chemical ligation procedure for any amino acid terminus. This flexible chemical ligation procedure provides a general synthetic route for various oligopeptide syntheses based on a convergent strategy. For example, for synthesis of a 48-residue oligopeptide, his convergent strategy requires only 4-5 steps compared with 48 steps using Merrifield’s classical linear peptide synthesis (>40% yield compared to 0.00001% yield, respectively). Furthermore, his most recent discovery provides a non-protecting peptide synthesis methodology, which affords the opportunity to reduce even more the length of synthetic routes. In addition, his new procedure can generate any cyclic lactam from linear peptides, which will solve several biologically important issues with respect to drug properties.
Thus, Yamamoto’s new innovation provides a paradigm shift of peptide synthesis to increase the scale from milligrams to tons. This will be quite beneficial for human beings in reducing the present high cost of medium and large peptide and antibody drugs, which will certainly improve the quality of life.
Asymmetric catalysis for C-C bond formation by chiral Lewis acids and Brønsted acids:
Among Yamamoto’s many superb contributions on basic Lewis acid catalysts the following are especially worthy of mention. In what is likely to become his most significant chemical legacy, Yamamoto has formulated a new paradigm for the chiral catalysis of reactions of main group elements by demonstrating chiral Lewis acid and/or Brønsted acid catalyzed asymmetric processes. In the early 1980s, he first introduced chiral binaphthol as a key ligand for chiral Lewis acid catalysts. This work was the forerunner of a vast quantity of present-day research on the C2 symmetry based chiral Lewis acid catalyst, now known as privileged ligands. Based on his knowledge of organoaluminum chemistry, he designed an organoaluminum catalyst for asymmetric hetero-Diels-Alder reaction in 1988. It was his Brønsted acid-Lewis acid combined system, however, which offered him a unique opportunity as the most efficient asymmetric carbon-carbon formations based on Lewis acid catalyst. Thus, his discovery of tartaric acid based catalyst (CAB catalyst) and amino acid based catalyst (oxaborolidine-type catalyst) led to the first and the most general enantioselective Diels-Alder reaction of a broad range of dienes and dienophiles. The same catalyst was shown to be the first one efficient for asymmetric aldol, ene, and allylation reactions. His recently uncovered silver catalyzed aldol and allylation process has provided a new entry to the creation of a quaternary carbon stereogenic center for asymmetric synthesis. A similar concept was employed for his catalytic asymmetric protonation under acidic conditions, which is capable of creating a long sought proton whichinduced asymmetric and biomimetic polyene cyclization. The use of 8-hydroxyquinole based chiral Lewis acid catalysis was his recent contribution to acid catalysis. The catalyst is designed as a rigid metal complex of cis-β-configuration, which makes the metal center of C1 chirality. The ligand turned out to be a brand new “privileged ligand” for asymmetric synthesis: catalytic asymmetric pinacol coupling, NH reaction, Mukaiyama-Michael addition, Pudovik reactions, Strecker reaction, hydrocyanation, Nagata-Michael addition, and Nitroso-Diels-Alder reaction are now able to proceed with complete enantioselectivity. In fact, most of theasymmetric carbon-carbon bond formation processes recognized today arebased on Yamamoto’s early discoveries.
Even more recently, he designed several chiral Brønsted acid catalysts with high reactivity for various asymmetric transformations. The original Akiyama-Terada catalyst is able to only nitrogen molecules. However, his phosphoramide catalyst could activate oxygen molecules and greatly expand the utility of the catalyst. This field of chemistry is now growing rapidly and he is the pioneer of this important area of chiral super Brønsted acid catalysis.
General foundation of acid catalysis:
Professor Yamamoto’s contribution to organic chemistry is not limited to asymmetric synthesis. However, the above contribution to asymmetric acid catalysis was based on his pioneering study in Lewis acid reagents. He was intrigued by the chemistry of the carbonyl compound-Lewis acid complex and introduced the unusually bulky organoaluminum reagents, methylaluminum bis(2,6-di-tert-butyl-4-methylphenoxide) (MAD) and aluminum tris(2,6-diphenylphenoxide) (ATPH). These reagents were successfully utilized for the selective alkylation of cyclic ketones and aldehydes to generate equatorial alcohol and an anti-Cram type product, respectively, for trans– and cis-selective Claisen rearrangement, for regioselective and exo-selective Diels-Alder reaction, and for epoxide-aldehyde rearrangement. The ATPH-aromatic carbonyl complex reacts with nucleophiles selectively at the para-position of the aromatic ring to generate cyclohexadiene derivatives. Besides these unexpected contributions to Lewis acid chemistry, his research in the area of organoaluminum chemistry has had a great impact on synthetic organic chemistry. The strong Lewis acidity of organoaluminum compounds appears to account for their strong tendency to form a stable 1:1 complex. Thus, the coordination of Lewis acid to molecules invariably causes a change of reactivity, and though coordinated by Lewis acid the group may be activated or deactivated depending upon the type of reaction. Furthermore, with the coordination of organic molecules an auxiliary bond can become coupled to the reagent and promote the designed reaction. In short, the reagents make a combined Lewis acid-Lewis base attack on a substrate with less activation energy, a field opened by Yamamoto’s early and highly original studies which began in 1973. His aluminum amide reagents for epoxide rearrangement, biogenetic-type terpene synthesis, and the Beckmann rearrangement-alkylation reaction sequence are notable examples. Even more recently, Lewis acid coordinated heterocyclic compounds are able to activate the specific position of the molecule for CH activation which originated Yamamoto’s Lewis acid chemistry. Based on these careful investigations of selective Lewis acid/Lewis base complexation, he proposed several basic principles for acetal chemistry, which are now used in the selective ring opening and alkylation processes for modern organic synthesis.
Direct condensation of carboxylic acids by alcohols or amines is the most important transformation of organic synthesis. Yamamoto found Lewis acid catalyst could play an important role in esterification and amidation processes. For example, his zirconium- or hafnium-catalyzed esterification and boron-catalyzed amidation are ground-breaking studies.
Finally, using this crucial information of Lewis acid and Brønsted acid catalysis, he recently achieved super silyl (tris(trimethylsilyl)silyl) chemistry which can realize double or triple aldol reaction in a single pot to generate a number of stereogenic centers in the molecule. Otherwise unattainably high diastereoselectivity in this cascade reaction makes this process a so-called “second generation of Mukaiyama aldol reaction”, which can make up to aneleven hydroxyl polyketide structure in three steps in a stereospecific manner. These findings open a possibility for a polyketide synthesizer, heretofore only dreamed of.
Other catalytic asymmetric transformations:
Professor Yamamoto also contributes significantly in the area of catalytic asymmetric oxidation reactions. For example, the nitroso-aldol reaction originated from his invention of 10 years ago. And asymmetric homo and bisohomoallylic alcohol was achieved in his laboratory for the first time. His tungsten chemistry is a real ground breaking discovery for oxidation using this non-toxic metal catalyst. Sequential epoxidation/ring opening will be used for a new strategy to generate >99.9%ee of the amino alcohol synthesis. The following is a list of catalytic asymmetric processes developed by Professor Yamamoto: O-nitro aldol and N-nitroso aldol synthesis; Nitroso-Diels-Alder reaction; epoxidations of homoallylic, and bishomoallylic alcohol; Asymmetric SN2 cross coupling with carbonyl and allylic nucleophiles. All of these reactions are unique and robust for modern organic synthesis.
Professor Yamamoto haspublished over >560 papers and over 140 reviews (50 inJapanese) which have been cited >30,000 times with anh-index of 96 ( for papers alone) and 113 including reviews and books.
His contributions have been recognized by his being a recipient of, among others: the Prelog Medal (1993), the Chemical Society of Japan Award (1995), Le Grand Prix de la Fondation Maison de la Chimie (2002), National Prize of Purple Medal (Japan) (2002), the Tetrahedron Prize for Creativity in Organic Chemistry (2006), the Japan Academy Award (2007), Grand Prize of Synthetic Organic Chemistry of Japan (2009), the ACS Award for Creative Work in Synthetic Organic Chemistry (2009), Fellow of American Academy Arts and Science (2011), Noyori Prize (2011), Fujiwara Prize (2012), Roger Adams Award (2017), The Order of the Sacred Treasure, Gold Rays with Neck Ribbon (2018), Person of Cultural Merit (2018), and University Professor Nagoya University (2019).
Selected publications (Yamamoto):
[1] Asymmetric cyclization of unsaturated aldehydes catalyzed by a chiral Lewis acid. Tetrahedron Lett, , 26, 5535, (1985). [2] Asymmetric hetero-Diels-Alder reaction catalyzed by chiral organoaluminum reagent. J. Am. Chem. Soc., 110, 310 (1988). [3] Acyloxyborane: An activating device for carboxylic acids. J. Am. Chem. Soc., 110, 6254 (1988) [4] Designer Catalysis: Combined Acid Catalysis for Asymmetric Synthesis. Angew. Chem. Int. Ed. 44, 1924-1942 (2005). [5] Oxazaborolidine-Derived Lewis Acid Assisted Lewis Acid as a Moisture-Tolerant Catalyst for Enantioselective Diels–Alder Reactions. Angew. Chem. Int. Ed. Enl., 44, 1484-1487 (2005). [6] Brønsted Acid Catalysis of Achiral Enamine for Regio- and Enantioselective Nitroso Aldol Synthesis. J. Am. Chem. Soc., 127, 1080 (2005). [7] Design of Chiral N-Triflyl Phosphoramide as a Strong Chiral Brønsted Acid and its application to Asymmetric Diels-Alder Reaction, J. Am. Chem. Soc. 128, 9626 (2006). [8] Asymmetric Conjugate Addition of Silyl Enol Ethers Catalyzed by Tethered Bis(8-Quinolinolato) Aluminum Complexes, J. Am. Chem. Soc. 129, 742-743, (2007). [9] Regioselective and Asymetric Diels-Alder Reaction of 1- and 2-Substituted Cyclopentadienes Catalyzed by a Brønsted Acid Activated Chiral Oxazaborolidine, J. Am. Chem. Soc., 129, 9536-9537 (2007). [10] Catalytic Enantioselective Pudovik Reaction of Aldehydes and Aldimines with Tethers Bis(8-quinolinato) (TBOx) Aluminum Complex. J. Am. Chem. Soc., 130, 10521-10523 (2008). [11] Cationic-Oxazaborolidine-Catalyzed Enantioselective Diels-Alder Reaction of ,β-Unsaturated Acetylenic Ketones. Angew. Chem. Int. Ed., 48, 8060-8062 (2009). [12] Dual-Activation Asymmetric Strecker Reaction of Aldimines and Ketimines Catalyzed by a Tethered Bis(8-quinolinolato) Aluminum Complex. J. Am. Chem. Soc., 131, 15118-15119 (2009). [13] Lewis Acid Catalyzed Inverse-Electron-Demand Diels-Alder Reaction of Tropones. J. Am. Chem. Soc., 131, 16628-16629 (2009). [14] Rapid and Stereochemically Flexible Synthesis of Polypropionates: Super-Silyl-Governed Aldol Cascades. Angew. Chem. 124, 1978–1982 (2012). [15] Ten Years Research in Chicago, Tetrahedron, 69, 4503-4515 (2013). [16] Tungsten catalyzed oxidation and ring opening to generate >99.9%ee product, J. Am. Chem. Soc., 136, 1222-1225 (2014). [16] Nickel-Catalyzed Regio- and Enantioselective Aminolysis of 3,4-Epoxy Alcohols, Wang, C.; Yamamoto, H., J. Am. Chem. Soc., 137, 4308-4311 (2015). [17] Chiral Bronsted Acid as a True Catalyst: Asymmetric Mukaiyama Aldol and Hosomi-Sakurai Allylation Reactions, Sai, M. Yamamloto, H., J. Am. Chem. Soc., 137,7091-7094 (2015). [18] Gadolinium-Catalyzed Regio- and Enantioselective Aminolysis of Aromatic trans-2,3-Epoxy Sulfonamides, Wang, C.; Yamamoto, H., Angew. Chem. Int. Ed., 54, 8760-8763 (2015). [19] Catalytic Enantioselective Nitroso Diels-Alder Reaction, Maji, B.; Yamamoto, H., J. Am. Chem. Soc., 137, 15957-15963 (2015). [20] Design of a New Bimetallic Catalyst for Asymmtric Epoxidation and Sulfoxidation, Bhadra, S., Akakura, M.; Yamamoto, H., J. Am. Chem. Soc., 137, 15612-15615. (2015) [21] Catalytic Enantioselective Nitroso Diels-Alder Reaction, Maji, B.; Yamamoto, H., J. Am. Chem. Soc., 137, 15957–15963 (2015). [22] Hyroxy-directed amidation of carboxylic acid esters using a tantalum alkoxide catalyst, Tsuji, H.; Yamamoto, H., J. Am. Chem. Soc., 138, 14218-14221 (2016). [23] Catalytic Asymmetric bromocyclization of pplyenes, Ramesh, S.; Yamamoto, H., J. Am. Chem. Soc., 139, 1460-1463 (2017). [24] Chiral Phosphoric Acid-Catalyzed Kinetic Resolution via Amide Bond Formation, Shimoda, Y.; Yamamoto, H., J. Am. Chem. Soc., 139, 6855-6858 (2017). [25] Substrate-Directed Catalytic Selective Chemical Reactions, Sawano, T.; Yamamoto, H., J. Org. Chem., 83(9), 4889-4904 (2018).
CURRICULUM VITAE of Hisashi Yamamoto
Professor and Director, Molecular Catalyst Research Center, Chubu University
Professor Emeritus, The University of Chicago
Professor Emeritus, Nagoya University
Personal Data
Born: July 16, 1943 (Kobe, Japan)
Citizenship: Japan
Current Address:
Chubu University, Molecular Catalyst Research Center
1200 Matsumoto, Kasugai, 487-8501 Japan
+81 568 51 9440 , home: +81 52 217 1984 cell: +81 90 9129 1867
hyamamoto@isc.chubu.ac.jp
The University of Chicago, Department of Chemistry
5735 South Ellis Avenue, Chicago, IL 60637, USA
yamamoto@uchicago.edu
Education
| B. S. | Kyoto University, 1967 (Prof. H. Nozaki, Thesis Director) |
| Ph. D. | Harvard University, 1971 (Prof. E. J. Corey, Thesis Director) |
Professional:
| 1971-1972 | Researcher, Toray Industries, Inc. (Prof. J. Tsuji, Adviser) |
| 1972-1976 | Instructor, Kyoto University (Prof. H. Nozaki, Adviser) |
| 1976-1977 | Lecturer, Kyoto University |
| 1977-1980 | Associate Professor, University of Hawaii |
| 1980-1983 | Associate Professor, Nagoya University |
| 1983-2002 | Professor, Nagoya University |
| 2003- | Professor Emeritus, Nagoya University |
| 2002-2012 | Professor, The University of Chicago |
| 2012- | Professor Emeritus, The University of Chicago |
| 2012- | Professor and Director of Molecular Catalyst Research Center, Chubu University |
| 2012- | Research Supervisor, JST Crest Project of Molecular Technology |
| 2014- | Research Supervisor, JST-ANR Joint Project of Molecular Technology |
| 2016-2018 | President of Chemical Society of Japan |
Publication
- >560 original papers and >140 reviews
- h-index: 98 (Web of Science, only for journal), 115 (Google, with books).
Membership
- The American Chemical Society, American Academy of Arts and Sciences
- American Association for the Advancement of Science, The Chemical Society of Japan
- The Pharmaceutical Society of Japan, The Society of Synthetic Organic Chemistry, Japan
- The Royal Society of Chemistry, London, Kinki Chemical Society, Japan
- The Engineering Society of Japan
- EU Academy
Editorship
Organic Syntheses, Board of Editors, 1988-1993, Advisory Board,1993-present
Synlett, Board of Editor, 1989-
Tetrahedron: Asymmetry, Consulting Editor, 1990-
J. Am. Chem. Soc., Editorial Advisory Board, 1994-1999
J. Chem. Soc., Chem. Commun., Regional Advisory Board, 1994-1996
Bull. of the Korean Chemical Society, International Advisory Board, 1998-2005
Organic Letters, Advisory Board, 1999-presnt
Journal of Oleo Science, Editorial Advisory Board, 2001-
European Journal of Organic Chemistry, Advisory Board, 1999-
Encyclopedia of Reagents for Organic Synthesis, International Advisory Board, 1992-1995
Molecules Online, Springer, 1998-1999
Topics in Current Chemistry, Springer, Board Member,1997-2014
Advanced Synthesis & Catalysis, Advisory Board, 2001-2011
Synfacts, Board of Editor, 2002-2014
Central European Science Journals, Advisory Board, 2002-
Tetrahedron and Tetrahedron Letters, Advisory Board, 2002-
Bulletin of the Chemical Society of Japan, Editorial Advisory Board, 2005-
Chemistry – An Asian Journal, International Advisory Board, 2006-
Chemistry Letters, Advisory Board, 2010-
The Chemistry Record, Editor in Chief, 2010-2018
Academic Awards and Honors:
The Chemical Society of Japan Award for Young Chemist, 1977.
IBM Science Award, 1988, Houkou Award, 1991, Chunichi Award, 1992.
Prelog Medal, 1993, Merck-Schuchardt Lectureship, 1994.
The Chemical Society of Japan Award, 1995. Toray Science and Technology Award, 1997
Max-Tishler Prize, 1998, Le Grand Prix de la Fondation Maison de la Chimie, 2002,
Tetrahedron Chair, 2002. Medal of Honor with Purple Ribbon (Japan), 2002
Molecular Chirality Award, 2003, Fellow of American Association for the Advancement of Science, 2003, Yamada Prize,
2004, Tetrahedron Prize, 2006, The Karl-Ziegler Professorship, 2006,
The Japan Academy Award, 2007, Humboldt Research Award, 2007,
Honorary Member of the Chemical Society of Japan, 2008
ACS Award for Creative Work in Synthetic Organic Chemistry, 2009
Grand Prize of Synthetic Organic Chemistry of Japan, 2009
Member of American Academy of Arts and Sciences, 2011,
Noyori Prize, 2011,Fujiwara Prize, 2012
ACS Roger Adams Prize, 2017
Honorary Member of the Pharmaceutical Society of Japan, 2017
Orders of the Sacred Treasure, 2018
The Person of Cultural Merit, 2018
Barluenga Lectureship medal, 2018
Member of EU Academy of Sciences, 2019
Plenary and Name Lectures (International):
| 1979 | Pacific Coast Lecturer, USA |
| 1979 | PAC Meeting, Honolulu, USA |
| 1982 | IUPAC Conference on Organic Synthesis, Tokyo |
| 1983 | IUPAC Conference on Organometallic Chemistry Directed Toward Organic Synthesis, France |
| 1984 | Annual Meeting of Pharmaceutical Society of Japan, Tokyo |
| 1985 | Euchem Stereochemistry Conference at Burgenstock, Switzerland |
| 1985 | Annual Meeting of Chemical Society of Japan, Tokyo |
| 1986 | Annual Meeting of Chemical Society of Korea, Seoul |
| 1986 | Gordon Conference on Stereochemistry, USA |
| 1986 | Hoechst Conference on Stereochemistry, Germany |
| 1987 | Annual Meeting of Agricultural Society of Japan, Tokyo |
| 1987 | IUPAC Conference on Organometallic Chemistry Directed Toward Organic Synthesis, Canada |
| 1987 | Organic Synthesis Lecturer, University of California, Berkeley |
| 1987 | Syntex Distinguished Lecturer, Colorado State University |
| 1987 | Sheffield Stereochemistry Symposium, UK |
| 1987 | Western Switzerland 3e Cycle Lecturer |
| 1988 | Karl Pfizer Visiting Professor, MIT |
| 1988 | First Organic Reaction Lecturer, USA |
| 1988 | IUPAC Conference on Natural Product, Kyoto |
| 1988 | NATO Conference on Stereochemistry, Greece |
| 1988 | International Symposium of Acid-Base Catalysis, Sapporo |
| 1989 | Annual Meeting of Chemical Society of Japan, Kyoto |
| 1989 | Visiting Professor of Universite Louis Pasteur, Strasbourg |
| 1989 | 11th International Symposium of Synthesis in Organic Chemistry, Oxford, UK |
| 1989 | Progress and Prospects in Organic Synthesis, Lausanne and Champery, Switzerland |
| 1989 | PAC Meeting, Honolulu |
| 1990 | Fifth Japan-Korea Seminar on Organic Chemistry, Dae Jeon , Korea |
| 1990 | The American Chemical Society, Aldrich Award Symposium, Boston |
| 1990 | Midwestern Distinguished Lecturer, USA |
| 1990 | Third Belgian Organic Synthesis Symposium, Louvain-La-Neuve, Belgium |
| 1990 | Eighth International IUPAC Conference on Organic Synthesis, Helsinki, Finland |
| 1990 | The Second International Symposium on the Chemical Synthesis of Antibiotics and Related Microbial Products, Oiso, Japan |
| 1990 | Annual Meeting of Chemical Society of Japan, Hiroshima |
| 1990 | Special Symposium of Pharmaceutical Society of Japan, Tokyo |
| 1991 | Annual Meeting of Pharmaceutical Society of Japan, Tokyo |
| 1991 | Symposium of Ohio State University, Recent Advances in Asymmetric Synthesis, USA |
| 1991 | Syntex Distinguished Lecturer at University of Colorado, Boulder, USA |
| 1991 | First Anglo-Norman Organic Chemistry Colloquium, Rouen, France |
| 1991 | Japan-US Seminar, Selectivity in Synthetic and Bioorganic Chemistry, Tokyo |
| 1991 | Otuka Symposium on Asymmetric Reactions and Molecular Recognition, Tokushima |
| 1991 | The 1991 Josef Fried Symposium of Bioorganic Chemistry, Chicago |
| 1992 | Annual Chemical Congress of the Royal Society of Chemistry, Manchester |
| 1992 | Nozaki Conference, Yokohama |
| 1992 | Gordon Conference (Organic Reaction Mechanism), New Hampton School |
| 1992 | 7th International Symposium on Molecular Recognition and Inclusion, Kyoto |
| 1992 | 6th Japan-Korea Organic Chemistry Symposium, Nagoya |
| 1992 | First International Symposium on Organic Synthesis, Tokyo |
| 1992 | 7th Johnson Symposium, Stanford, CA. |
| 1992 | nternational Symposium on Inorganic and Organic Chemistry, Taipei, Taiwan |
| 1992 | Tsing-Hua Symposium on Organic and Inorganic Chemistry, Hsinchu, Taiwan |
| 1993 | Annual Meeting of Chemical Society of Japan, Tokyo |
| 1993 | Bader Symposium, Harvard University, Cambridge, USA |
| 1993 | Gordon Conference (Natural Product), New Hampton School, USA |
| 1993 | Fourth International Symposium on Chiral Discrimination, Quebec, Canada |
| 1993 | Prelog Medal Lecture, Zurich, Switzerland |
| 1994 | Annual Meeting of New Swiss Chemical Society, Switzerland |
| 1994 | Merck-schuchardt Lectureship, Germany |
| 1994 | The 4th International Conference on Chemical Synthesis of Antibiotics and related Microbial Products, Nashville, USA |
| 1994 | Pre-IUPAC International Symposium on Metal-Mediated Organic Synthesis, India |
| 1995 | Annual Meeting of Chemical Society of Japan, Tokyo |
| 1995 | Merck-Frosst Lecturer, Alberta University, Canada |
| 1995 | Enantioselective C-C bond formation in synthesis, SCI, London, UK |
| 1995 | SFC-Rhone Poulene Lecturer, France |
| 1996 | Organic Synthesis Lecturer, University of California, Irvine |
| 1996 | Annual Conference of Polymer Science, Nagoya, Japan |
| 1996 | 50th Anniversary Conference of Korean Chemical Society, Seoul, Korea |
| 1996 | Fargo Conference on Main Group Chemistry, North Dakota, USA |
| 1996 | ISCHIA Advanced School of Organic Chemistry, Ischia, Italy |
| 1997 | Gilbert Stork Lecturer, Columbia University, New York, USA |
| 1997 | H.C. Brown Lecturer, Purdue University, USA |
| 1997 | 36th IUPAC Congress, Geneva, Switzerland |
| 1997 | 9th International Symposium on Chiral Discrimination, Nagoya, Japan |
| 1997 | William G. Dauben Lecturer, University of California, Berkeley, USA |
| 1997 | Bio-Mega Lecturer, Montreal, Canada |
| 1997 | 5th Max Tishler Memorial Symposium, Tokyo |
| 1998 | Max Tishler Prize Lecture, Harvard, USA |
| 1998 | 1998 Hofmann Distinguished Lecture, Imperial College, London, UK |
| 1998 | 12th IUPAC Conference on Organic Synthesis, Venice, Italy |
| 1998 | 9th International Symposium on Novel Aromatic Compounds, Hong Kong |
| 1999 | Novartis Lectureship, Switzerland |
| 1999 | 37th IUPAC Congress, Berlin, Germany |
| 1999 | 218th National meeting of American Chemical Society, New Orleans, USA |
| 2000 | Taiwan National Lectureship, Taiwan |
| 2000 | Columbia IAP Lecturer, USA |
| 2000 | Kharasch Lecturer, University of Chicago, USA |
| 2001 | PAC meeting, Honolulu, USA |
| 2001 | UCSD-Dupont symposium, La Jolla, USA |
| 2001 | 84th CSC Conference, Montreal, Canada |
| 2001 | Annual Meeting of Chemical Society of Japan, Chiba, Japan |
| 2001 | ICCOC-GTL-10, Bordeaux, France |
| 2002 | The Nagoya COE-RCMS Conference, Japan |
| 2002 | Cram Stereochemistry Symposium, UCLA, USA |
| 2002 | BOSS IX Meeting, Namur, Belgium |
| 2002 | Gordon Conference, Reaction and Processes, RI, USA |
| 2002 | Oppolzer Lectures 2002, Genève, Switzerland |
| 2003 | Otto-Bayer Lecturer 2003, Cologne, Germany |
| 2003 | 15th International Symposium on Chirality, Shizuoka, Japan |
| 2003 | 18th International Symposium on Synthesis in Organic Chemistry, Cambridge, U. K. |
| 2003 | Komppa Centenary Symposium, Espoo, Finland |
| 2003 | Boehringer Ingelheim Lecturer, Alberta, Canada |
| 2004 | The 17th Annual Organic Chemistry Day, Missouri, USA |
| 2004 | 2004 CU-Roche Colorado Symposium on Synthetic Organic Chemistry, Boulder, Colorado |
| 2004 | 10th Meeting of the French-American Chemical Society, Charleston, SC |
| 2004 | CMDS Symposium, Seoul, Korea |
| 2004 | The Fourth International Symposium on Chemistry and Biological Chemistry of Vanadium, Szged, Hungary |
| 2004 | Pettit Centennial Lecturer, University of Texas |
| 2004 | Merck Lecturer, University of Puerto Rico |
| 2005 | Pfizer Lecturer, Harvard University |
| 2005 | 125th Annual Meeting of Pharmaceutical Society in Japan |
| 2005 | Distinguished Merck Frosst Lectureship, Canada |
| 2005 | Novartis Lecturer, University of Illinois at Urbana-Champaign |
| 2005 | OMCOS-13, Genève, Switzerland |
| 2005 | The 22nd Summer Seminar on Synthetic Organic Chemistry, Japan |
| 2005 | Eli Lilly Lecturer, University of Pittsburg |
| 2005 | International SFB-Symposium, Aachen, Germany |
| 2005 | The 4th COE-Chem6 International Symposium, Tokyo, Japan |
| 2005 | PAC Meeting, Inorganic and Polymer sections, Honolulu, USA |
| 2005 | PAC Meeting, Polymer Chemistry, Honolulu, USA |
| 2006 | COE meeting, Nagoya University, Nagoya Japan |
| 2006 | Reilly Lecturer, University of Notre Dame |
| 2006 | 7th Annual Florida Heterocyclic Conference, Gainesville, USA |
| 2006 | Appleton Lecturer, Brown University, USA |
| 2006 | Eli Lilly Lecturer, Yale University, USA |
| 2006 | Challenges in Contemporary Chemistry Symposium, University of Michigan |
| 2006 | Banyu Symposium, Fukuoka, Japan |
| 2006 | Balticum Orgnicum Syntheticum, Tallinn, Estonia |
| 2006 | Organocatalysis in Organic Synthesis, Glasgow, UK |
| 2006 | FrontChem2006, Zushi, Japan |
| 2006 | American Chemical Society, National Meeting, San Francisco |
| 2006 | 5th International Symposium on Chemistry and Biological Chemistry of Vanadium, San Francisco |
| 2006 | Inaugural Negishi-Brown Lecture, Purdue |
| 2006 | Merck-Frosst Lecture, Univdersite de Montreal, Canada |
| 2006 | Novartis Lecturer, Boston College, Boston |
| 2006 | Karl-Ziegler-Professorship, Max Planck Institute, Germany |
| 2006 | 6th Tateshina conference on Organic Chemistry, Tateshina, Japan |
| 2006 | 10th International Kyoto conference on New Aspects of Organic Chemistry, Japan |
| 2006 | Pierre Fabre Lecturer, French Chemical Society, Paris, France |
| 2007 | American Chemical Society, National Meeting, Chicago |
| 2007 | Organic Chemistry, present and future, Louvain-la-Neuve, Belgium |
| 2007 | International Conference on Asymmetric Organocatalysis, Otsu, Japan |
| 2007 | The 29th annual Princeton ACS Fall Organic Symposium, Princeton |
| 2007 | Invited Lecture Series, Academy of Science of the Czech Republic |
| 2007 | The 5th Kitasato Chemistry Symposium, Tokyo |
| 2007 | Organic Synthesis Mini Symposium, Chiba |
| 2007 | The Japan Academy Prize Symposium, Riken, Japan |
| 2008 | Schulich Symposium on Asymmetric Catalysis, Haifa, Israel |
| 2008 | Roche Distinguished Lecturer, Colorado |
| 2008 | Bristol-Myers Squibb Lecturer, Berkeley |
| 2008 | Eli Lilly Lecturer, University of Toronto |
| 2008 | FITS Symposium, Geneva, Switzerland |
| 2008 | Banyu Foundation Symposium, Sapporo, Japan |
| 2008 | Suzuki Kunio Symposium, Tokyo, Japan |
| 2008 | Tarrant visiting professor of organic chemistry, University of Florida |
| 2008 | International Conference on Asymmetric Catalysis, Kanazawa, Japan |
| 2008 | Lecturer of Institute of Academia Sinica, Taipei |
| 2009 | LOST II, Alain Krief Symposium, Namur, Belgium |
| 2009 | Chicago Organic Chemistry Symposium, Northwestern University |
| 2009 | The Third Novel Chiral Chemistry, Japan 2009, Tokyo |
| 2009 | The Lambert Lecture, Boston University |
| 2009 | The Gilman Lecturer, Iowa State University |
| 2009 | The Roche Lecturer, Scripps Institute, USA |
| 2009 | Tetrahedron Symposium, Paris |
| 2009 | Nanyang Tec. University Opening Symposium, Singapore |
| 2009 | ACS meeting, Milwaukee, WI |
| 2009 | 13th Asian Chemical Congress, Shanghais, China |
| 2009 | The H. Smith Broadbent Lecture, BYU, Salt Lake |
| 2009 | Eminent Scholar Lecturer, The University of Arizona, Tucson |
| 2009 | KISPOC, Kyushu, Japan |
| 2010 | The Chemical Record Lecturer, Osaka, Japan |
| 2010 | The AkzoNobel, Novartis and Shasun Lecture, Bristol, UK |
| 2010 | Burgenstock Conference, Guest of Honor, Brunnen, Switzerland |
| 2010 | N. C. Yang Lecturer, Taipei |
| 2010 | 93rd Canadian Chemistry Conference, Toronto, Canada |
| 2010 | ISOm, Organocatalyst Symposium, Muelheim, Germany |
| 2011 | Frontier in Chemical Research Lecturere, Texas A&M |
| 2011 | 19th Lilly symposium, Madrid, Spain |
| 2011 | Gassman Lectureship, University of Minnesota, Minneapolis |
| 2011 | First Mexican Meeting on Pure and Applied Chemistry, Mexico City |
| 2011 | 42nd National Organic Symposium, Princeton |
| 2011 | European Science Foundation, COST conference, Maratea, Italy |
| 2011 | Ei-Ichi Negishi Nobel Prize Symposium, Purdue, IN |
| 2011 | First Germany-Japan Organocatalytic Symposium, Kyoto, Japan |
| 2012 | Abbott Lecture, Yale University, New Haven |
| 2012 | Vertex Lecture, UCIrvine |
| 2012 | Natural Product Symposium, Kyushu, Japan |
| 2012 | 4th EurCheMS, Prague, Czech |
| 2012 | BMS Lecture, Boston College |
| 2012 | Roche Lecture, Columbia University |
| 2013 | International Conference of Catalysis, Cologne |
| 2013 | 25th Banyu Symposium, Sappro, Japan |
| 2013 | International Conference, Prague |
| 2014 | Academia Sinica, Taipei |
| 2014 | Gordon Conference, USA |
| 2014 | International Conference of Catalysis, Chicago, USA |
| 2015 | Tetrahedron Symposium, Tokyo, Japan |
| 2015 | WPI Lecture, Tohoku University, Japan |
| 2015 | Kanagawa symposium, Kanagawa, Japan |
| 2015 | Riken Symposium, Saitama, Japan |
| 2015 | Naito Symposium, Sapporo, Japan |
| 2015 | Negishi-Brown Lecturer, USA |
| 2015 | ELP Lectureship, Kyoto University |
| 2015 | IKOCK Symposium, Alkara, Spain |
| 2015 | Pachifichem 2015, Honolulu, USA |
| 2016 | NTech International Symposium, Nagoya |
| 2016 | Molecular Science Symposium, Okazaki |
| 2017 | Chirality Symposium, Tokyo |
| 2017 | 45th National Organic Chemistry Symposium, Davis, California |
| 2018 | The Nanyan Chemistry Distinguished Lecture, Singapore |
| 2018 | Barluenga Lectureship Medal, Spain |