Synthesis and in Vitro Cytotoxicity Evaluation of Jadomycins
Erika Iwasaki; Yoshimi Shimizu; Yusuke Akagi; Toshiya Komatsu
Chem. Pharm. Bull, Sep. 2023, [Reviewed]
Jadomycins, which are benzo[b]phenanthridine-type alkaloids isolated from Streptomyces venezuelae ISP5230, exhibit cytotoxic activity against multidrug-resistant breast cancer cells. We have previously achieved the total synthesis of jadomycins using the direct arylation of juglone as a key step. In this study, we achieved the total synthesis of jadomycin T and jadomycin aglycons using L-threonine and 1-amino-2-propanol as nitrogen sources. Additionally, we evaluated the cytotoxic activity of eight compounds, including glycosides, jadomycin T, and their corresponding aglycons, in eight types of tumor cells. The evaluated jadomycins tended to exhibit stronger cytotoxic activity as aglycons than as glycosides. Although the presence of a 1,3-oxazolidine ring derived from an amino acid was not essential, the presence of the 1,3-oxazolidine ring showed strong activity when the ring had a carboxyl group. Furthermore, compared to the non-natural isomer at a different position on the phenolic hydroxyl group, the naturally occurring phenanthroviridin aglycon exhibited stronger cytotoxic activity. In addition, this study suggests that jadomycins may become lead compounds for the treatment of brain tumors; however, further studies on their ability to penetrate the blood-brain barrier are required.

Total synthesis of jadomycins A, B, and L-digitoxosyl-phenanthroviridin
Yusuke Akagi; Yuta Mori; Yudai Sato; Erika Iwasaki; Toshiya Komatsu
Tetrahedron Letters, Jul. 2022, [Reviewed]

Total Synthesis of Phenanthroviridin Aglycon and Its Analog
Yusuke Akagi; Kohei Harasawa; Toshiya Komatsu
Asian Journal of Organic Chemistry, May 2021, [Reviewed]

Palladium-catalyzed arylation of 1,4-naphthoquinones with aryl iodides and its synthetic application to the benzo[b]phenanthridine skeleton
Yusuke Akagi; Toshiya Komatsu
Tetrahedron Letters, Oct. 2020, [Reviewed]

Palladium-Catalyzed β-Arylation of Cyclic α,β-Unsaturated O-Methyl Oximes with Aryl Iodides
Yusuke Akagi; Shiori Fukuyama; Toshiya Komatsu
Chemical and Pharmaceutical Bulletin, 01 Mar. 2020, [Reviewed]

Synthesis and Aldose Reductase Inhibitory Activity of Botryllazine A Derivatives
Ryota Saito; Kana Ishibashi; Maiko Noumi; Sota Uno; Shoko Higashi; Masaru Goto; Shunsuke Kuwahara; Toshiya Komatsu
Chemical and Pharmaceutical Bulletin, 01 Jun. 2019, [Reviewed]

Green fluorescent protein chromophore derivatives as a new class of aldose reductase inhibitors
Ryota Saito; Maiko Hoshi; Akihiro Kato; Chikako Ishikawa; Toshiya Komatsu
European Journal of Medicinal Chemistry, Jan. 2017, [Reviewed]

Molecular Structure of (1R*,8S*)-9-Amino-2,3,5,6,7,8-hexahydro-1H-cyclopenta(b)quinoline-1,8-diol.
Toshiya KOMATSU; Kimiko KOBAYASHI; Tadashi NAKATA; Masashi YANO; Ken-ichi SUZUKI
Analytical Sciences, 1996, [Reviewed]

Absolute Configuration of (+)-9-Amino-2,3,5,6,7,8-hexahydro-8-hydroxy-4-methyl-1H-cyclopenta(b)quinolinium Iodide.
Toshiya KOMATSU; Kimiko KOBAYASHI; Tadashi NAKATA; Mie KOBAYASHI; Ken-ichi SUZUKI
Analytical Sciences, 1996, [Reviewed]

Synthesis of Estimated Metabolites of 9-Amino-2, 3, 5, 6, 7, 8-hexahydro-1H-cyclopenta [b] quinoline Monohydrochloride Monohydrate (NIK-247). II. Synthesis of Dihydroxylated Metabolites
Toshiya KOMATSU; Masashi YANO; Mitsuo IWAMOTO; Mie KOBAYASHI; Kenichi SUZUKI
YAKUGAKU ZASSHI, 1995, [Reviewed]
The two dihydroxylated metabolites of 9-amino-2,3,5,6,7,8-hexahydro-1H-cyclopenta [b] quinoline monohydrochloride monohydrate (NIK-247), which is a new drug for the treatment of dementia, were synthesized to determine their chemical structures. Reduction of the tricyclic diketone, 9-amino-2,3,6,7-tetrahydro-1H-cyclopenta [b] quinoline-1,8 (5H)-dione, with equivalent molar of NaBH_4,afforded the racemic two alcohols, (±)-9-amino-2,3,5,6,7,8-hexahydro-8-hydroxy-1H-cyclopenta [b] quinolin-1-one and (±)-9-amino-2,3,5,6,7,8-hexahydro-1-hydroxy-1H-cyclopenta [b] quinolin-8-one. (+)-9-Amino-2,3,5,6,7,8-hexahydro-8-hydroxy-1H-cyclopenta [b] quinolin-1-one was obtained by optical resolution of the corresponding racemic hydroxyketone using (-)-di-p-toluoyl-L-tartaric acid. The optically active dihydroxylated metabolites were obtained by reduction of the (+)-8-hydroxy-1-one with NaBH_4.

Synthesis of Estimated Metabolites of 9-Amino-2, 3, 5, 6, 7, 8-hexahydro-1H-cyclopenta [b] quinoline Monohydrochloride Monohydrate (NIK-247). I. Synthesis of Mono-hydroxylated Metabolites
Toshiya KOMATSU; Masashi YANO; Haruaki INADA; Mitsuo IWAMOTO; Kazuo OKADA; Kenichi SUZUKI
YAKUGAKU ZASSHI, 1995, [Reviewed]
The two mono-hydroxylated metabolites of 9-amino-2,3,5,6,7,8-hexahydro-1H-cyclopenta [b] quinoline monohydrochloride monohydrate (NIK-247), which is a new drug for the treatment of dementia, were synthesized to determine their chemical structures. Reduction of two tricyclic ketones, 9-amino-1,2,3,5,6,7-hexahydro-8H-cyclopenta [b] quinolin-8-one and 9-amino-2,3,5,6,7,8-hexahydro-1H-cyclopenta [b]-quinolin-1-one, with NaBH_4 afforded the corresponding racemic alcohols. The optically active mono-hydroxylated metabolites, (+)-9-amino-2,3,5,6,7,8-hexahydro-1H-cyclopenta [b] quinolin-8-ol and (+)-9-amino-2,3,5,6,7,8-hexahydro-1H-cyclopenta [b] quinolin-1-ol, were obtained by optical resolution of each racemic alcohol using (+)-di-p-toluoyl-D-tartaric acid.

Synthetic study of marine macrolide swinholide A. stereocontrolled synthesis of the C11 - C23 segment
Tadashi Nakata; Toshiya Komatsu; Kazuo Nagasawa; Haruo Yamada; Takashi Takahashi
Tetrahedron Letters, Oct. 1994, [Reviewed]

Synthetic Study of Marine Macrolide Swinholide A. Stereocontrolled Synthesis of the C11-C32 Segment.
Tadashi NAKATA; Toshiya KOMATSU; Kazuo NAGASAWA
Chemical and Pharmaceutical Bulletin, 1994, [Reviewed]
The C24-C32 segment 4 of swinholide A (1) was stereoselectively synthesized starting from (S)-methyl 3-hydroxybutyrate, and the convergent synthesis of the C11-C32 segment 5 was accomplished via stereoselective aldol condensation of 3 and 4

Studies on tetrahydroisoquinolines. XXVII A synthesis of 3-hydroxyaporphines and 3-hydroxyhomoaporphines.
HIROSHI HARA; HIROSHI SHINOKI; TOSHIYA KOMATSU; OSAMU HOSHINO; BUNSUKE UMEZAWA
Chemical and Pharmaceutical Bulletin, May 1986, [Reviewed]
Acid treatment of o-quinol acetates (2a and 2b) derived from 5-hydroxy-1-benzyltetrahydroisoquinolines (3a and 3b) gave the corresponding 3-hydroxyaporphines (4a and 4b) in high yield.Similarly, the 3-hydroxyhomoaporphines (4c, 4d, and 4e) were excusively synthesized from the corresponding 1-phenethyl o-quinol acetates (2c, 2d, and 2e). On the other hand, no C-noraporphine was formed from the 1-aryl o-quinol acetate (2f); instead, the p-quinone (11) was generated.

医薬品原薬・中間体製造におけるスケールアップとトラブル対策
Contributor
Apr. 2008
9784781300252

二方向型ニトロアルドール反応の研究 ―芳香族アルデヒドを用いた検討 ―　　　　　　　　　　　　　　　
28 Mar. 2025

Dalomycin T の合成研究　　　　　　　　　　　　　　　
27 Mar. 2025

ベンゾ[b ]フェナントリジンアルカロイドの合成と活性評価　　　　　　　　　　　　　　　
28 Oct. 2024

Dalomycin T の合成研究　　　　　　　　　　　　　　　
30 Mar. 2024

二方向型ニトロアルドール反応の研究 ―基質の検討と立体選択性―　　　　　　　　　　　　　　　
30 Mar. 2024

L-Digitoxosyl-phenanthroviridinの全合成と活性評価　　　　　　　　　　　　　　　
16 Sep. 2023

Moverastin誘導体の合成研究（２）　　　　　　　　　　　　　　　
16 Sep. 2023

Studies on bi-directional nitroaldol reaction (5)　　　　　　　　　　　　　　　
Erika Iwasaki; Futaba Nakazawa; Fumihiro Fukuhara; Rio Kadowaki; Yusuke Akagi; Toshiya Komatsu
27 Mar. 2023

Synthetic studies on Moverastin derivatives　　　　　　　　　　　　　　　
Keisuke Morita; Kazuki Hara; Ryota Hosoya; Mei Kashihara; Yusuke Akagi; Toshiya; Komatsu
26 Mar. 2023

Total Synthesis of L-Digitoxosyl-phenanthroviridin　　　　　　　　　　　　　　　
Hiroki Shimizu, Yuta Mori, Yudai Sato, Kohei Harasawa, Erika Iwasaki, Yusuke Akagi, Toshiya Komatsu
26 Mar. 2023

フェナントロビリジン関連化合物の合成と活性評価　　　　　　　　　　　　　　　
Sep. 2022

フェナントロビリジンアグリコンの全合成　　　　　　　　　　　　　　　
Mar. 2022

二方向型ニトロアルドール反応の研究（４）－二方向型ニトロアルドール付加体の立体構造の決定－　　　　　　　　　　　　　　　
Mar. 2022

1,4-ナフトキノン類の直接的なアリール化反応の検討　　　　　　　　　　　　　　　
Mar. 2021

二方向型ニトロアルドール反応の研究（３）　　　　　　　　　　　　　　　
Mar. 2021

環状α,β-不飽和オキシムエーテルのβ位アリール化反応の検討　　　　　　　　　　　　　　　
Mar. 2020

二方向型ニトロアルドール反応の研究（２）　　　　　　　　　　　　　　　
Mar. 2020

オキシムエーテルのβ位アリール化反応の検討　　　　　　　　　　　　　　　
Sep. 2019

ケトンおよびオキシムエーテルの 位置選択的なアリール化反応の検討　　　　　　　　　　　　　　　
Mar. 2019

二方向型ニトロアルドール反応の研究－分子間ダブルニトロアルドール反応の開発－　　　　　　　　　　　　　　　
Mar. 2019

アルドース還元酵素阻害活性を有する GFP クロモフォアモデルの合成と構造活性相関　　　　　　　　　　　　　　　
Sep. 2016

アルドース還元酵素阻害活性を有する botryllazine B 類似体の合成と構造活性相関　　　　　　　　　　　　　　　
May 2016

Synthesis and aldose reductase inhibitory activity of botryllazine B analogues having bicyclic heterocycles on the C6 position: A structure- activity relationship study　　　　　　　　　　　　　　　
Dec. 2015

Highly potent aldose reductase inhibitors derived from Botryllazine B　　　　　　　　　　　　　　　
Mar. 2014

Effects of NIK-626, a Dual Inhibitor of Thromboxane Synthetase and 5-Lipoxygenase on Airway Inflammatory Model in Guinea Pigs　　　　　　　　　　　　　　　
Sep. 2000

Pharmacological Profiles of NIK-626, a New Dual Inhibitor of Thromboxane Synthetase and 5-Lipoxygenase　　　　　　　　　　　　　　　
Sep. 2000

Preswinholide Aの全合成　　　　　　　　　　　　　　　
Nov. 1996

Synthetic Study of Swinholide A and Related Compounds　　　　　　　　　　　　　　　
Jul. 1994

スウィンホライドAの合成研究　　　　　　　　　　　　　　　
Mar. 1994

スウィンホライドAの合成研究（３）　　　　　　　　　　　　　　　
Mar. 1993

スウィンホライドAおよびその関連化合物の 合成研究　　　　　　　　　　　　　　　
Oct. 1992

スウィンホライドAの合成研究（２）　　　　　　　　　　　　　　　
Mar. 1992

還元型ホモプロアポルフィン類の合成研究II　　　　　　　　　　　　　　　
Mar. 1991

スウィンホライドAの合成研究　　　　　　　　　　　　　　　
Mar. 1991

還元型ホモプロアポルフィン類の合成研究　　　　　　　　　　　　　　　
Aug. 1990

サイトファイシンCの合成研究　　　　　　　　　　　　　　　
Aug. 1990

サイトファイシン類の合成研究　　　　　　　　　　　　　　　
Mar. 1990

セラミックス担体固定化プルラナーゼによる分岐 シクロデキストリンの連続合成　　　　　　　　　　　　　　　
Apr. 1988

固定化プルラナーゼによる分岐シクロデキストリンの連続合成　　　　　　　　　　　　　　　
Mar. 1988

A Synthetic Approach to Dihydrohomoproaporphines　　　　　　　　　　　　　　　
Dec. 1984

ジヒドロホモプロアポルフィン類の合成研究　　　　　　　　　　　　　　　
Mar. 1984