The Nakanishi Symposium
on Natural Products & Bioorganic Chemistry

March 23, 2022

Sponsored by
The Chemical Society of Japan&The American Chemical Society

Takenori Kusumi
Professor Emeritus, Tokushima University
Special Professor, Tokyo Institute of Technology■EDUCATION
B.Sci.
Department of Chemistry, Tokyo University ofEducation
1966
Ph.D. Chemistry, Tokyo University of Education
1973■CAREERTokyo University of Education
1973–1976
Assistant Professor, Department of ChemistryTsukuba University
1976–1992
Lecturer, Department of ChemistryColumbia University
1979–1980
Postdoctoral fellow, Department of Chemistry, K. Nakanishi’sgroup－2－

Tokushima UniversityProfessor, Faculty of Pharmaceutical Sciences
Tokyo Institute of Technology
Special Professor, Department of Chemistry■RESEARCH TOPICS
 Structure elucidation of natural products
 Absolute configuration of organic compounds
 Chiral anisotropic reagents for absolutedetermination
 NMR spectroscopy

1992–2008
2008–2021

configuration■SELECTED PUBLICATIONS
1. Novel Diterpenes with a Cyclobutenone Moiety from the Brown
Alga Pachydictyon coriaceum, M. Ishitsuka, T. Kusumi, H.
Kakisawa, Y. Kawakami, Y. Nagai, T. Sato, J. Org. Chem., 1983,48, 1937.
2. High-field FT NMR Application of Mosher’s Method. The
Absolute Configurations of Marine Terpenoids, I. Ohtani, T.
Kusumi, Y. Kashman, H. Kakisawa, J. Am. Chem. Soc., 1991, 113,4092.
3. Cyanoviridin RR, a Toxin from the Cyanobacterium (Blue-greenAlga) Microcystis viridis, T. Kusumi, T. Ooi, M. M. Watanabe, H.
Takahashi, H. Kakisawa, Tetrahedron Lett., 1987, 28, 4695.
4. Microviridin, a Novel Tricyclic Depsipeptide from the Toxic
Cyanobacterium Microcystis viridis, M. O. Ishitsuka, T. Kusumi,
H. Kakisawa, K. Kaya, M. M. Watanabe, J. Am. Chem. Soc., 1990,112, 8180.
5. The Structures of Quatromycins A1, A2, and A3: Novel
Macrocyclic Antiviral Antibiotics Possessing Four TetronicMoieties, T. Kusumi, A. Ichikawa, H. Kakisawa, M. Tsunakawa,
M. Konishi, T. Oki, J. Am. Chem. Soc., 1991, 113, 8947.
6. NMR Spectroscopic Determination of the Absolute Configurationof Chiral Sulfoxides via N- (Methoxyphenylacetyl)sulfoximines, T.
Yabuuchi, T. Kusumi, J. Am. Chem. Soc., 1999, 121, 10646.
■AWARD
The Chemical Society of Japan Award for Creative Work for 2004.

－3－

― Table of Contents ―Profile of Prof. Takenori Kusumi
Prize Winner of the Nakanishi Prize 2022

… 2

Program of the Award Ceremonyof the Nakanishi Prize & Nakanishi Symposium… 5“NMR-based Determination of Absolute and Relative
Configuration Inspired by the Kusumi's Method”
Prof. Michio Murata (Osaka University)… 6“Studies on Biosynthesis of Marine Toxins Basedon The Chemical Structures”
Prof. Mari Yotsu-Yamashita (Tohoku University）… 7“Marine Natural Product Chemistry: Isolation,
Structural Determination, Synthesis, andMolecular Mechanism of Biological Action”
Prof. Hideo Kigoshi (Tsukuba University）… 8“Discovery of Marine Natural Products: Standing on
the Shoulders of Giants”
Prof. Shigeki Matsunaga (The University of Tokyo)… 9Award Lecture“Perpetually Fascinated by Natural Products
Chemistry: with the Advancement of NMR”
Prof. Takenori Kusumi(Professor Emeritus, Tokushima University,
Special Professor, Tokyo Institute Technology)… 10－4－

Nakanishi Symposium 2022
Organized by：Nakanishi Symposium Organizing Committee
Co-organized by: Chemical Society of Japan,
Division of Natural Products Chemistry & Biological Science

DateMarch 23rd, 2022, 13:00–15:40 Zoom Webinar
Program■13:00-13:20 Award Ceremony of Nakanishi Prize 2022
Congratulatory Address: Prof. Hiroaki Suga,President-elect, The Chemical Society of Japan
Prize Winner of the Nakanishi Prize 2022:
Prof. Takenori Kusumi; Professor of Tokyo Institute of Technology■13:20-15:40
Nakanishi Symposium
Presider Prof. Noritaka Chida (Keio University)
13:30- “NMR-based Determination of Absolute and Relative
Configuration Inspired by the Kusumi's Method”
Prof. Michio Murata (Osaka University)
13:45- “Studies on Biosynthesis of Marine Toxins Based on The
Chemical Structures”
Prof. Mari Yotsu-Yamashita (Tohoku University)
14:00- “Marine Natural Product Chemistry: Isolation, Structural
Determination, Synthesis, and Molecular Mechanism ofBiological Action”
Prof. Hideo Kigoshi (Tsukuba University)
14:15- “Discovery of Marine Natural Products: Standing on theShoulders of Giants”
Prof. Higeki Matsuhaga (The University of Tokyo)
14:30-14:40 ---Break--■14:40- Award Lecture
Presider Prof. Keisuke Suzuki; Tokyo Institute of Technology“Perpetually Fascinated by Natural Products Chemistry:
with the Advancement of NMR”
Prof. Takenori Kusumi
15:35- Closing Remarks by Prof. Koichi Fukase (Osaka University)－5－

NMR-Based Determination of Absolute andRelative Configuration Inspiredby the Kusumi's Method
Michio Murata
Graduate School of Science, Osaka University
murata@chem.sci.osaka-u.ac.jp
Determination of stereochemistry of natural products and synthetic
intermediates is one of the major topics of instrumental analyticalmethods. With the availability of high-field and high-resolution NMR
instruments, which have been realized in the last 20-30 years, Dr.
Kusumi has succeeded in establishing a reliable method forstereochemistry analysis by optimizing the classical Mosher method.
This achievement has greatly accelerated the progress of structuredetermination and synthesis of natural products in the past 30 years.
Inspired by the so called Kusumi method, various conformational
analysis techniques have been developed, including those invented byhimself.
Recently, new methodologies have been used that do not require chiralauxiliaries; e.g., computer-based approaches to deduce NMR chemical
shifts of organic compounds have become more reliable. The scope andlimitations of these methods will also be discussed.
References:
1. Ohtani, I., Kusumi, T., Kashman, Y., Kakisawa, H. J. Am. Chem. Soc.,
1991, 113, 4092–4096.
2. 岩下孝、楠見武徳、村田道雄 「特論 NMR 立体化学」講談社, 2012年.

－6－Studies on Biosynthesis of Marine Toxins
Based on The Chemical Structures
Mari Yotsu-Yamashita
Graduate School of Agricultural Science, Tohoku Universitymari.yamashita.c1@tohoku.ac.jp
Tetrodotoxin (TTX) and saxitoxin (STX) are potent Nav blockers. TTX,a puffer fish toxin, has been identified in a wide range of marine animals
and terrestrial amphibians. Biosynthesis of TTX has been a mystery forlong time. We have approached this problem by identifying many
structurally related compounds to TTX from puffer fish and newts.
Based on the structures of these compounds, multiple oxidation steps
from the spiro-fused bicyclic guanidino compounds have beensuggested in TTX biosynthesis in marine environments.1 In terrestrial
environments, C5-C10 directly bonded TTX analogues and bi- and tricyclic guanidino compounds have been identified from newts,
Concerning STX
suggesting monoterpene origin of TTX.2
biosynthesis, putative biosynthetic genes and functional expression ofsome corresponding enzymes have been reported. The mechanism oftricyclic structure formation in STX biosynthesis and order of oxidation
steps are the current issues of interest. We are challenging to solve thesequestions using synthetic intermediates and originally developed
analytical methods.3
References:
1. N.
Ueyama,K.
Sugimoto, Y. Kudo,
K. Onodera, Y. Cho,K.
Konoki,T.
Nishikawa, M. YotsuYamashita,
Chem.
Eur. J., 2018, 24, 7250-7258.
2. Y. Kudo, C.T. Hanifin, M. Yotsu-Yamashita, Org. Lett., 2021, 23,3513-3517.
3. S. Tsuchiya, Y. Cho, R. Yoshioka, K. Konoki, K. Nagasawa, Y.
Oshima, M. Yotsu-Yamashita, Angew. Chem. Int. Ed., 2017, 56,5327-5331.

－7－

Marine Natural Product Chemistry: Isolation,
Structural Determination, Synthesis, and Molecular
Mechanism of Biological Action
Hideo Kigoshi
Faculty of Pure and Applied Sciences, University of Tsukuba
kigoshi@chem.tsukuba.ac.jp
Marine natural products provide us scientific knowledge to understandlife. There have been interesting compounds with unique structures andremarkable bioactivites from marine organisms.
Aplyronine A is a potent antitumor macrolide isolated from theJapanese sea hare Aplysia kurodai. We determined the structure inspectroscopic and organic synthetic manners. Total synthesis of thenatural product and its artificial analogs was achieved, which provided
the SAR information. Bioorganic study using artificial analogs andchemical probes revealed that an aplyronine A–actin–tubulin ternarycomplex disrupts microtubule dynamics to lead tumor cells toapoptosis. In thispresentation,synthesis ofaplyronine analogs
and bioorganic study
using the analogs
will be discussed.
References:
1.
2.
3.

Yamada, K.; Ojika, M.; Kigoshi, H.; Suenaga, K. Nat. Prod. Rep.,
2009, 26, 27-43.
Kita, M.; Kigoshi, H. Nat. Prod. Rep., 2015, 32, 534-542.
Ohyoshi, T.; Kigoshi, H. Chem. Lett., 2021, 50, 580-584.

－8－Discovery of Marine Natural Products:
Standing on the Shoulders of Giants
Shigeki Matsunaga
Department of Aquatic Bioscience, The University of Tokyo
assmats@mail.ecc.u-tokyo.ac.jp
Compounds with a vast structural diversity have been isolated frommarine organisms, especially sponges. Appropriately chosen methods
should be used for their precise structure elucidation. Two examples
from our group will be discussed.
Marine sponge Cladocroce sp. contained a new glycosylated bipolar
sphingolipid. The relative configuration of 1,2-amino-alcohol unit ineach end was assigned after converting to the bis-oxazolidinone
derivative. The absolute configuration of the secondary alcohol in eachend was determined by the modified Mosher’s method. There was an
isolated ketone in the middle of a long aliphatic chain, whose position
was determined after converting to a mixture of positional isomers ofthe amides.1
Sesquiterpens related to manoalide and with less oxidation state wereisolated from a marine sponge Luffariella sp. There was a chiraldihydropyran ring whose absolute configuration was assigned by a
combination of asymmetric dihydroxylation and analysis of the 1H
NMR data. The conclusion drawn from this analysis was confirmed by
the modified Mosher’s method.2
References:
1.
2.

K. Sugawara, H. Watarai, Y. Ise, H. Yokose, Y. Morii, N. Yamawaki,
S. Okada, S. Matsunaga, Marine Drug, 2021, 9, 287.
D. Kanki, K. Imai, Y. Ise, S. Okada, S. Matsunaga, J. Nat. Prod.,
2021, 84, 1676-1680.

－9－Perpetually Fascinated by Natural Products
Chemistry: with the Advancement of NMR
Takenori Kusumi
Professor Emeritus, Tokushima University
Special Professor of Tokyo Institute of Technology
kusumi.t.ab@m.titech.ac.jp―Dedicated to late Professor Harry Stone Mosherー
Historically, natural products have been the centerpiece of organic
chemistry, because they exist in common organisms surrounding humanbeings, some showing fascinating colors, and some having medicinalactivities. Among the properties of natural products, the complexityof their chemical structures has intrigued organic chemists, who workin syntheses and structure analyses.
We have been studying the structure elucidation of natural products,
mainly of those separated from marine organisms. The works wereheavily dependent on NMR spectroscopy, starting from 60 MHz in the
1960th to modern 600 MHz instruments. The first significant results
were obtained from the works on the seaweeds of Dictyota family,
which produced a series of unique diterpenes composed of 4- to 11memberbed rings.1 With the aid of newly developed pulse sequencessuch as TOCSY, ROESY, HSQC and HMBC, the structures of theunusual compounds such as a marine alkaloid composed of a guanidine
and a spermidine groups2, a hepatotoxic monocyclic peptide3 and atricyclic depsipeptide4 from a lake-water cyanobacterium, a novel
macrocyclic antiviral antibiotics possessing four tetronic moieties,5 anda highly unsaturated antibiotic alkaloid (using INADEQUATE)6 wereelucidated.

－10－In the middle of 1980th, most of the compounds we isolated from marineorganisms turned out to be ‘known compounds’. In fact, one of thegraduate students was sighing in front of the heap of cembranoids(monocyclic diterpenoids), whose structures were all known. There
was no way to publish the known structures in a journal. She, however,found that, although the relative stereochemistry of them was clarified,the absolute configurations were not elucidated. Therefore, wefocused on the method capable of determination of their absoluteconfigurations. That was the time when the modified Mosher’s
method7 was established based on Professor Mosher’s originalfindings.8 The method is easy to use and reliable, it was utilized worldwidely until recently.
The method depends on the anisotropic effect of the phenyl group of
the MTPA moiety.
Later, we developed new chiral reagents
possessing a naphthyl or an anthracenyl groups, which shows stronger
anisotropic effect.9 Also, the methods for absolute configurations ofchiral carboxylic acids10 and sulfoxides11 were newly developed.
Because collection of marine organisms became more and moredifficult from the ecological point of view, our focus was shifted tomarine-derived fungi, which were easily cultivated in the laboratory.12

References:
1.

2.

3.

(a) M. Ishitsuka, T. Kusumi, J. Tanaka, H. Kakisawa, Chemistry Lett.,
1982, 1517. (b) T. Kusumi, D. M. Nkongolo, M. Goya, M. Ishitsuka,T. Iwashita, H. Kakisawa, J. Org. Chem., 1986, 51, 384 andreferences cited therein.
(a) I. Ohtani, T. Kusumi, Y. Kashman, H. Kakisawa, J. Am. Chem.
Soc., 1991, 113, 4092. (b) I. Ohtani, T. Kusumi, H. Kakisawa, Y.
Kashman, S. Hirsh, J. Am. Chem. Soc., 1992, 114, 8472.
T. Kusumi, T. Ooi, M. M. Watanabe, H. Takahashi, H. Kakisawa,Tetrahedron Lett., 1987, 28, 4695.

－11－4.

M. O. Ishitsuka, T. Kusumi, H. Kakisawa, K. Kaya, M. M. Watanabe,
J. Am. Chem. Soc., 1990, 112, 8180.
5. T. Kusumi, A. Ichikawa, H. Kakisawa, M. Tsunakawa, M. Konishi,
T. Oki, J. Am. Chem. Soc., 1991, 113, 8947.
6. T. Kusumi, T. Ooi, M. R. Wälchli, H. Kakisawa, J. Am. Chem. Soc.,
1988, 110, 2954.
7. I. Ohtani, T. Kusumi, Y. Kashman, H. Kakisawa, J. Am. Chem. Soc.,
1991, 113, 4092.
8. J. A. Dale, H. S. Mosher., J. Am. Chem. Soc. 1973,95, 512.
9. T. Kusumi, T. Ooi, Y. Ohkubo, T. Yabuuchi, Bull. Chem. Soc, Jpn,2006, 79, 965 and references cited therein.
10. T. Yabuuchi , T. Kusumi, J. Org. Chem., 2000, 65, 397.
11. T. Yabuuchi, T. Kusumi, J. Am. Chem. Soc., 1999; 121, 10646.
12. (a) M. Iida, T. Ooi, K. Kito, S. Yoshida, K. Kanoh, Y. Shizuri, T.
Kusumi, Org. Lett., 2008, 10, 845. (b) R. Ookura, K. Kito, T. Ooi,M. Namikoshi, T. Kusumi, J. Org. Chem., 2008, 73, 4245.

－12－Michio Murata: born in 1958, Osaka,graduated and PhD from Tohoku University(Prof. Takeshi Yasumoto), Research Staff,Suntory Institute for Bioorganic Research(1983-1985, Prof. Nakanishi), ResearchAssociate, Tohoku University (1985-1993,Prof. Yasumoto), Post-Doctoral Research
Fellow, NIDDK, National Institutes ofHealth (1989-1991, Dr. J. W. Daly), Associate
Professor, The University of Tokyo (19931999, Prof. Kazuo Tachibana), Professor,
Department of Chemistry, Osaka University (1999- ).

Mari Yotsu-Yamashita: born in 1961 andgraduated from Tohoku University (B. 1984),
PhD from Tohoku University (1989, Prof.
Takeshi Yasumoto), Junior researcher(Technical official) (1984-1998), Visiting
Scholar, Department of Chemistry, Ohio
State University (Prof. Viresh H. Rawal)(1994-1995), Associated Professor, Faculty ofAgriculture, Graduate School of Agricultural
Science, Tohoku University (1998-2004),
Professor, Graduate School of Agricultural
Science, Tohoku University (2004- ). JSBBA Award for Young Scientists(2000).

－13－

Hideo Kigoshi: born in Gifu, 1959 andgraduated from Nagoya University (B. 1981)
PhD, Nagoya University (Prof. KiyoyukiYamada) 1989, Assistant Professor, Faculty ofScience, Nagoya University (1984-1994),
Postdoctoral fellow, Harvard University(1990-1991, Prof. E.J. Corey), Associate
Professor, Faculty of Science (1994-1998) andResearch Center for Materials Science,Nagoya University (1998-2000), Professor,
Department of Chemistry (2000-2011) andFaculty of Pure and Applied Sciences, University of Tsukuba (2011- ).
Chemical Society of Japan Award for Young Chemists (1993).

Shigeki Matsunaga: born in Tokyo in 1957
and educated at The University of Tokyo (B.,1979; M., 1981; PhD, 1984) (Prof. ShojiKonosu). JSPS Postdoctoral Fellow, TheUniversityofTokyo(1984-1988),
postdoctoral fellow at University of Hawaii(1988-1989, Prof. R. E. Moore), andNational Cancer Center Research Institute(1990-1991, Dr. Hirota Fujiki), AssistantProfessor, Faculty of Agriculture, The
University of Tokyo (1991-1995), Associate
Professor (1995-2004), and Professor (20042022) at the same campus. Throughout his research career he has beenfascinated by the incredibly designed structures of biologically active
natural products.

－14－

The Recipients of the Prize hereto are:1996 Yoshimasa Hirata*
1997 Frank H. Westheimer
1998 Albert J. Eschenmoser*
1999 Jeremy R. Knowles
2000 Satoshi Ōmura*2001 John D. Roberts
2002 Sir Jack Baldwin*
2003 A. Ian Scott2004 Isao Kitagawa*2005 Stephen J. Benkovic
2006 Takeshi Yasumoto*2007 Hung-wen Liu
2008 Michel Rohmer*
2009 JoAnne Stubbe2010 Shosuke Yamamura*2011 C. Dale Poulter2012 Daisuke Uemura*2013 Arthur G. Palmer, III
2014 Jerrold Meinwald*2015 Fred McLafferty
2016 Shoichi Kusumoto*2017 Martin Gruebele
2018 Nobuyuki Harada*
2019 Lewis E. Kay2020 Yoshito Kishi*
2021 Mei Hong2022 Takenori Kusumi**Selection and presentation made by the Chemical Society of Japan.

Organizing Committee:◆Chairperson: Noritaka Chida (Keio University)◇Members:
Ikuro Abe (The University of Tokyo)
Hirokazu Arimoto (Tohoku University)
Koichi Fukase (Osaka University)
Hirokazu Kawagishi (Shizuoka University)
Michio Murata (Osaka University)
Junko Okanda (Shinshu University)
Hiroyuki Osada (RIKEN)
Keisuke Suzuki (Tokyo Institute of Technology)
Minoru Ueda (Tohoku University)
Mari Yotsu-Yamashita (Tohoku University)