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Synthetic Study on Some Drugs and Bioactive Compounds Inspired by AI System SYNSUP

髙畠 哲彦 大阪府立大学 DOI:info:doi/10.24729/00017396

2021.05.11

概要

1.1 Artificial Intelligence
In modern society, computers and networks are common infrastructure. Advanced
software has been developed for various purposes in every industrial field. The first
electronic general-purpose digital computer, ENIAC, was released in 19461. Similar to
many other scientific and technological innovations, it was intended for military purposes
such as the calculation of ballistic trajectory and simulation of nuclear fission. In the
meantime, the famous British mathematician and computer scientist Alan Turing, who
presented the theoretical concept of the stored-program computer2, formulated a chess
program as early as 19483. Once personal computers became available, chess programs
that operated at the amateur level were released. Since then, the algorithm has been
improved as microchip technology has advanced. To display its power, IBM, the computer
giant, challenged the reigning world chess champion, Garry Kasparov, to a match against
their chess-specialized computer Deep Blue. While Kasparov won the first challenge,
Deep Blue succeeded in winning the second match in 19974. However, there was some
controversy regarding to what degree the computer was backed up by human intervention
in terms of the selection of opening moves and suggestions in the middle of the game5. In
recent years some chess programs have been developed that could compete with chess
grandmasters. The evaluation of chess positions has been improved through machine
learning of the records of games and trial matches with other computer chess software, but
it is still beyond the power of machine learning technology to trace all the possible chess
moves from the beginning to the end.
Artificial intelligence (AI) research has been carried out in various fields and yet, the
degree of achievements was much less than previously anticipated, and this brought about
disappointments in its history (Figure 1-16). There have been two so-called “AI winters”
where research activities were diminished due to criticism and financial setbacks. Boom 1
has been labeled as “GOFAI,” which stands for “Good Old-Fashioned AI.” The Samuel
Checkers playing program was among the world's first successful self-learning programs,
and as such, a very early demonstration of the fundamental concept of AI7a. In Boom 2
expert systems were developed, which was an approach to analyze the expertise of
humans and make judgment rules for the selection of candidate solutions. ...

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参考文献

Contributed papers to this thesis

1. Takabatake, T.; Yoneda, T.; Otsuka, J.; Kagawa, N.; Toyota, M. Artificial intelligence

designed drug synthesis: One-pot preparation of trans β-lactams and application to

cholesterol absorption inhibitor SCH 47949 synthesis. Tetrahedron Lett. 2019, 60,

150942–150945.

2. Takabatake, T.; Yoneda, T.; Otsuka, J.; Kagawa, N.; Toyota, M. Artificial

intelligence-designed stereoselective one-pot synthesis of trans-β-lactams and its

application to cholesterol absorption inhibitor SCH 47949 synthesis. Heterocycles

2020, 100, 60–84.

3. Takabatake, T.; Tomita, H.; Okada, S.; Hayashi, N.; Masuko, T.; Toyota, M.

Anticancer agent synthesis designed by artificial intelligence: Pd(OAc)2-catalyzed

one-pot preparation of biphenyls and its application to a concise synthesis of various

diazofluorenes. Tetrahedron Lett. 2020, 61, 152267.

4. Takabatake, T.; Fujiwara, K.; Okamoto, S.; Kishimoto, R.; Kagawa, N.; Toyota M.

Discovery of orthogonal synthesis using artificial intelligence: Pd(OAc)2-catalyzed

one-pot synthesis of benzofuran and bicyclo[3.3.1]nonane scaffolds. Tetrahedron Lett.

2020, 61, 152275.

Other contributed papers

(Refereed publication)

1. Nishimura, H.; Takabatake, T.; Kaku, K.; Seo, A.; Mizutani, J. A simple total synthesis

of (±)-δ-cadinene. J. Agric.Biol.Chem. 1981, 45, 1861-1864.

2. Takahashi, M.; Dogane, I.; Yoshida, M.; Yamachika, H.; Takabatake, T.; Bersohn, M.

The Performance of a Noninteractive Synthesis Program. J. Chem. Inf. Comput. Sci.

1990, 30, 436-441.

3. Takabatake, T.; Bersohn, M. Synthetic routes proposed by a noninteractive synthesis

program. Pure & Appl. Chem. 1990, 62, 1977-1979.

4. Dogane, I.; Takabatake, T.; Bersohn, M. Computer‐executed synthesis planning: a

progress report. Recl. Trav. Chim. Pays-Bas 1992, 111, 291-296.

124

5. Katouda, W.; Kawai, T.; Takabatake, T.; Tanaka, A.; Bersohn, M.; Gruner, D.

Distances in Molecular Graphs. J. Phys. Chem. A, 2004, 108, 8019-8026.

6. Tanaka, A.; Kawai, T.; Takabatake, T.; Oka, N.; Okamoto, H.; Bersohn, M. Synthesis

of an azaspirane via Birch reduction alkylation prompted by suggestions from a

computer program. Tetrahedron Lett. 2006, 47, 6733-6737.

7. Tanaka, A.; Kawai, T.; Takabatake, T.; Oka, N.; Okamoto, H.; Bersohn, M. Finding

synthetically versatile and common intermediates for multiple useful products with

the aid of a synthesis design system. Tetrahedron 2007, 63, 10226-10236.

8. Tanaka, A.; Kawai, T.; Fujii, M.; Matsumoto, T.; Takabatake, T.; Okamoto, H.;

Funatsu, K. Molecular centrality for synthetic design of convergent reactions.

Tetrahedron 2008, 64, 4602-4612.

9. Tanaka, A.; Kawai, T.; Matsumoto, T.; Fujii, M.; Takabatake, T.; Okamoto, H.;

Funatsu, K. Construction of a Statistical Evaluation Model Based on Molecular

Centrality to Find Retrosynthetically Important Bonds in Organic Compounds. Eur. J.

Org. Chem. 2008, 5995-6007.

10. Tanaka, A.; Kawai, T.; Matsumoto, T.; Takabatake, T.; Okamoto, H.; Funatsu, K.

Development of Evaluation Model for Strategic Sites in Synthetic Route Design

System AIPHOS. J. Computer Aided Chem. 2008, 9, 81-91.

11. Tanaka, A.; Kawai, T.; Takabatake, T.; Okamoto, H.; Bersohn, M. Selective Search

Focusing on Retro-Synthetically Important Bonds in A Synthesis Design System. J.

Computer Aided Chem. 2009, 10, 104-117.

12. Miyagi, T.; Okada, S.; Tada, N.; Sugihara, M.; Kagawa, N.; Takabatake, T.; Toyota, M.

Pd(OAc)2-catalyzed orthogonal synthesis of 2-hydroxybenzoates and substituted

cyclohexanones from acyclic unsaturated 1,3-carbonyl compounds. Tetrahedron Lett.

2019, 60, 1653–1657.

13. Mikami, S.; Okada, S.; Kishimoto, R.; Takabatake, T.; Toyota, M. Pd(OAc)2-catalyzed

one-pot preparation of anthranilates from acyclic unsaturated β-enamino esters.

Tetrahedron Lett. 2020, 61, 151659–151663.

125

(Not refereed publication)

14. 吉田元二, 高畠哲彦, 石田雅也「当社における合成反応設計システム」, 住友

化学, 1990, 1990-II, 39-64.

15. 高畠哲彦, 竹村年男, 銅金巌「有機合成デザイン―コンピュータと有機合成研

究者の棲み分けの時代の到来」 住友化学, 1994, 1994-I, 69-82.

16. 高畠哲彦 「有機合成研究におけるコンピューターケミストリーの利用」 (<連

載:コンピューターケミストリーとファインケミカル(4)-企業研究者のため

の実際的入門>) ファインケミカル, 2003 年 5 月 1 日・15 日合併号

17. Takabatake, T. SYNSUP: Synthetic Route Design System. Sumitomo Chemical, 2009,

2009-II, 38-47.

List of Presentations

1. Takabatake, T.; Kawai, T.; Tanaka, A.; Katouda, W.; Bersohn, M.; Gruner, D.

Synthesis Design System SYNSUP. The 27th Symposium on Chemical Information

and Computer Sciences, 2004, Tsukuba, Japan.

2. Takabatake, T.; Tanaka, A.; Kawai, T.; Bersohn, M. Synthesis Design System

SYNSUP and its Selective Search Strategy. The 32th Symposium on Chemical

Information and Computer Sciences, 2009, Yamaguchi, Japan.

3. Takabatake, T. Synthesis Design Systems and Their Practical Use in Synthetic

Research. The 34th Symposium on Chemical Information and Computer Sciences,

2011, Nagasaki, Japan.

4. 高畠哲彦 「ここまで来た合成経路設計システム―SYNSUP の現状報告―」(有

機合成夏季セミナー「明日の有機合成化学」,7), 2013 年 9 月 2~3 日, 大阪

書籍リスト

1. 高畠哲彦, 山近洋 「コンピュータによる有機合成」 (応用化学講座<4>有機合成化

学, 第 5 章), 1997, 209-247, 朝倉書店

126

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