著者

岩間 雄亮 岡野 健太郎 徳山 英利

出版者

社団法人 有機合成化学協会

雑誌

有機合成化学協会誌 (ISSN:00379980)

巻号頁・発行日

vol.71, no.9, pp.926-934, 2013-09-01

参考文献数

35

被引用文献数

6

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This review focuses on synthetic studies on mersicarpine that has a characteristic skeleton including seven-membered cyclic imine fused with indoline and δ-lactam. After a brief discussion of structural features and proposed biogenesis of this compound, several synthetic efforts toward construction of mersicarpine core are described. Total syntheses of mersicarpine are described including Kerr’s racemic synthesis utilizing a formation of seven-membered cyclic imine from α-hydroxyketone prepared by oxidation of indole, racemic syntheses of the Kerr’s synthetic intermediate by Zard and Han, the first enantiocontrolled total synthesis by Fukuyama based on the construction of seven-membered α-hydroxyimine by autoxidation of azepinoindole, and the second enantiocontrolled synthesis by Tokuyama employing a DIBALH-mediated ring-expansion reaction of cyclic ketoxime fused with indole.

著者

徳山 英利 中村 正治

出版者

The Society of Synthetic Organic Chemistry, Japan

雑誌

有機合成化学協会誌 (ISSN:00379980)

巻号頁・発行日

vol.63, no.5, pp.523-538, 2005-05-01 (Released:2009-11-13)

参考文献数

102

被引用文献数

16 20

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Among non-conventional stimulations to accelerate organic reactions, high-pressure, ultrasound irradiation, and microwave irradiation are representative methods and are now becoming more and more popular in laboratories. This review focuses on organic reactions under microwave irradiation since this technique has attracted broad range of interest from the scientific and practical viewpoints. After the brief description on the historical and theoretical backgrounds of the dielectric heating, microwave effects, practical aspects of microwave heating (choice of solvent and microwave reactors), scope, and limitations of microwave-assisted synthetic reactions are discussed.

著者

福山 透 徳山 英利 菅 敏幸 横島 聡 下川 淳

出版者

東京大学

雑誌

基盤研究(S)

巻号頁・発行日

2003

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本研究課題では、独自に開発した合成方法論、および独創性が高く高効率的な合成デザインによる、真に物質供給に耐えうる全合成法の開発を目的として、ヘテロ元素を含む高次構造天然物の全合成研究をおこなった。その結果、当研究室で独自に開発した芳香族アミノ化反応を用いることで、デュオカルマイシン、ヤタケマイシンを、不斉CH挿入反応によるジヒドロベンゾフラン環合成法を用いることでエフェドラジンA、セロトベニンを、ラジカル環化反応によるインドール合成法を用いることでストリキニーネ、コノフィリン、アスピドフィチンを、それぞれ合成することに成功した。また独創的合成デザインに基づき、FR901483、リゼルグ酸、モルヒネ、オセルタミビルの効率的合成法の開発に成功した。強力な抗腫瘍活性を有しながらも天然からは微量にしか得ることが出来ないヤタケマイシンにおいては大量合成にも成功し、市場における化合物供給にも耐えうる方法論を確立した。またタミフルについて、その副作用の原因究明のための研究に対して、活性化合物を提供した。セロトベニンの全合成では光学活性試料の合成に成功し、生合成経路におけるラセミ化機構の解明に大きな知見を与えることが出来た。また全合成の達成には至らなかったものの、レモノマイシン、UCS1025A、プラキニジンA、アルテミシジン、アニサチン、レペニンの合成研究を行い、有機合成上有用な知見を得ることが出来た。以上の研究成果が得られたことより、本研究課題の目的を十分達成することが出来たものと考えている。以上のように本研究課題の成果は、有機合成化学を基盤とした幅広い研究分野に対して、大きく貢献することができた。

著者

岡野 健太郎 徳山 英利 福山 透

出版者

天然有機化合物討論会

雑誌

天然有機化合物討論会講演要旨集

巻号頁・発行日

no.48, pp.175-180, 2006-09-15

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(+)-Yatakemycin (1), which was isolated from a culture broth of Streptomyces sp. TP-A0356, is an antitumor antibiotic that has a characteristic dienone cyclopropane ring found in duocarmycins and CC-1065. Among them, 1 has been shown to exhibit the most potent activity, and therefore has attracted a great deal of attention. The first total synthesis along with the revision of its structure and determination of the absolute configuration has recently been reported by Boger and co-workers. Herein, we describe an efficient total synthesis of 1 utilizing our copper-mediated amination for the construction of all five aryl-nitrogen bonds, allowing us to conduct a sub-gram-scale preparation of 1 in 16% overall yield over 17 steps (longest linear steps from the known starting compound 6). Synthesis of the left segment 3 commenced with dibromination of 6. Removal of the TFA group, and subsequent oxidation provided dihydroisoquinoline 7, which was readily converted to the cyclization precursor 9. The first amination reaction of 9 afforded indoline 10 with retention of the other bromo group. After conversion to the dehydroamino ester 12, the second amination was performed to provide dihydropyrroloindole 13. The Ns group and benzyl ester in 13 were then converted to Fmoc group and a methanethiol ester, respectively. Finally, an Fmoc-directed, regioselective demethylation was performed with BCl_3 to furnish the left segment 3. Our amination also proved to be highly effective for the construction of the middle segment 4. Cleavage of (S)-epichlorohydrin (18) with 2,6-dibromophenyllithium species 17 provided chlorohydrin 19, which was then converted to amination precursor 21. The crucial aryl amination took place smoothly to give tetrahydroquinoline 22. After Mizoroki-Heck reaction with a dehydroalanine derivative 23 and removal of the nosyl group, bromo group was introduced regioselectively. The second amination reaction at the sterically hindered position was achieved by using a stoichiometric amount of CuI to furnish the middle segment 4. The right-hand segment 5 was also prepared in a straightforward manner by using the aryl amination strategy. Three segments thus obtained were assembled to complete the total synthesis. After coupling of the middle segment 4 with the right segment 5, TBS ether 32 was converted into the mesylate 33. Subsequent hydrolysis provided 34, which was subjected to the condensation conditions with 3 without isolation. Two benzyl groups were then removed with BCl_3, in the presence of excess pentamethylbenzene as a scavenger of benzyl cation. Finally, spirocyclopropanation was carried out according to Boger's conditions to furnish (+)-1, which was identical in all respects to the natural product.