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| 1.
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Yamada, Fumio ; Kawanishi, Atsuko ; Tomita, Akiko ; Somei, Masanori
概要:
1-Hydroxy-2,3-dimethylindole (1) has been prepared for the first time. Under atmospheric oxygen, 1 was converted rapidly into 3-hydroxy-2,3-dimethyl- 3H-indole N-oxide (2). The structure was deduced, based on its products obtained
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by the reaction with Ac2O in pyridine and confirmed by X-ray single crystallographic analysis.
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| 2.
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Yamada, Koji ; Somei, Masanori
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Photoirradiation of 1-ethoxy-2-phenylindole in methanol and the reaction of 1-hydroxy-2-phenylindole with tosyl chloride
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produced 6-ethoxy- and 6-tosyloxy-2-phenylindoles, respectively, as minor products. The latter was derived to 6-ethoxy-2-phenylindole. The structure is determined by direct comparison of the spectral data with those of the authentic 4-, 5-, 6-, and 7-ethoxy-2-phenylindoles whose syntheses are reported in detail. © 2012 The Japan Institute of Heterocyclic Chemistry.
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| 3.
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Yamada, Fumio ; Fukui, Yoshikazu ; Iwaki, Takako ; Ogasawara, Sachiko ; Okigawa, Masaki ; Tanaka, Satomi ; Somei, Masanori
概要:
A simple and new method for the preparation of optically active methyl 3a-chloro-, 3a-bromo-, 3a-hydroxy-, and 3a-alkoxy
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-1,2,3,3a,8,8a-hexahydropyrrolo[2,3-b]indole-2-carboxylates has been developed. © 2006 The Japan Institute of Heterocyclic Chemistry All rights reserved.
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| 4.
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Fukui, Yoshikazu ; Somei, Masanori
概要:
金沢大学大学院自然科学研究科生理活性物質科学<br />金沢大学薬学部<br />3-Substituted (3S,6S)-6-(1-hydroxyindol-3-ylmethyl)-2,5-piperazinediones are pr
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epared for the first time. They are shown to be suitable intermediates for the synthesis of 3,10b-disubstituted (3S,5aR,10bS,11as)-1,3,4,5a,6,10b,11, 11a-octahydro-2H-pyrazino[1',2': 1,5]pyrrolo[2,3-b]indole-1,4-dione derivatives.
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| 5.
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Yamada, Fumio ; Goto, Aya ; Hasegawa, Masakazu ; Kobayashi, Kensuke ; Somei, Masanori ; 山田, 文夫 ; 染井, 正徳
概要:
金沢大学医薬保健研究域薬学系<br />Various nucleophiles, such as indole, 1,2,3-trimethoxybenzene, anisole, phenol, and pyrrole, reacted
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with 1-hydroxy-Nb-trifluoroacetyltryptamine under the presence of mesyl chloride to give novel series of (3a,8acis)- 1,2,3,3a,8,8a-hexahydropyrrolo[2,3-b]indoles having a substituent at the 3aposition. Their structures and by-products were strictly determined. © 2017 The Japan Institute of Heterocyclic Chemistry.<br />Embargo Period 12 months
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| 6.
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Yamada, Koji ; Yamada, Fumio ; Shiraishi, Takei ; Tomioka, Saori ; Somei, Masanori
概要:
1-Methoxy-6-nitroindole-3-carbaldehyde is proved to be a versatile electrophile and reacts regioselectively at the 2-pos
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ition with various types of nucleophiles providing 2,3,6-trisubstituted indole derivatives. The reaction is applicable for the preparation of a novel pyrimido[1,2-a]indole derivative. © 2009 The Japan Institute of Heterocyclic Chemistry All rights reserved.
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| 7.
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Yamada, Fumio ; Fukui, Yoshikazu ; Iwaki, Takako ; Ogasawara, Sachiko ; Okigawa, Masaki ; Tanaka, Satomi ; Somei, Masanori
概要:
金沢大学大学院自然科学研究科生理活性物質科学<br />金沢大学薬学部<br />A simple and new method for the preparation of optically active methyl 3a-chlor
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o-, 3a-bromo-, 3a-hydroxy-, and 3a-alkoxy-1,2,3,3a,8,8a-hexahydropyrrolo[2,3-b]indole-2-carboxylates has been developed. © 2006 The Japan Institute of Heterocyclic Chemistry All rights reserved.
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| 8.
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Yamada, Koji ; Tanaka, Yoshio ; Somei, Masanori
概要:
Nb-Acyl- and Nb-acyl-1-hydroxytryptamines are found to be novel and structurally simple (α2-blocker for the treatment of erectile dysfunction. © 2009 The Japan Institute of Heterocyclic Chemistry All rights reserved.
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| 9.
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Sato, Masako ; Suzuki, Yoshiaki ; Yamada, Fumio ; Somei, Masanori
概要:
Various derivatives of (6R (*),6aR (*))-6-chloro-6a-hydroxy-5, 6,6a,12-tetrahydroindolo[2,3-a]carbazole-5-one (8) and 6-
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cyano-5- hydroxyindolo[2,3-a]-carbazole (9) are prepared. Preparations of (6R (*),6aR (*),11aR (*))-6-chloro-11a-cyano-6a-hydroxy- (11) and 12-substituted 6-(Z)-aminomethylidene-5,6,6a, 11,11a,12-hexahydroindolo[2,3-a] carbazole-5-ones (15) are also reported. © 2010 The Japan Institute of Heterocyclic Chemistry Received.
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| 10.
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Somei, Masanori ; Yamada, Fumio ; Kato, Jun ; Suzuki, Yoshiaki ; Ueda, Yoshinori
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金沢大学大学院自然科学研究科生理活性物質科学<br />金沢大学薬学部<br />Their Diels-Alder reaction produced 11-alkyl-, 11-allyl-, and 11-β-glycosylindo
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lo[2,3-a]carbazoles. Formation of a novel 6,7-dihydro-13H-cyclopentano[mn]indolo[3,2-c]acridine derivative is also reported.
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| 11.
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Iwaki, Takako ; Yamada, Fumio ; Funaki, Shiho ; Somei, Masanori
概要:
金沢大学大学院自然科学研究科生理活性物質科学<br />金沢大学薬学部<br />Three methods have been newly developed for the synthesis of 1,2,3,3a,8,8a-hexa
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hydropyrrolo[2,3-b]indoles. Employing them, 3a-chloro-, 3a-bromo-, 3a-hydroxy-, and various 3a-alkoxy-1,2,3,3a,8,8a-hexahydropyrrolo[2, 3-b]indoles are now readily available.
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| 12.
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Yamada, Koji ; Yamada, Fumio ; Somei, Masanori
概要:
金沢大学大学院自然科学研究科生理活性物質科学<br />Nucleophiles react with 1-methoxy-3-(2-nitrovinyl)indole (3) at the 2-position regioselectiv
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ely in a dipolar aprotic solvent (DMF or HMPA), while in THF they undergo Michael addition to the β-carbon of nitrovinyl side chain. Depending on bases employed, the resultant Michael addition products (6d, 10, and 11) are found to undergo interesting cyclizations to give novel 3-substituted 1-methoxyindoles (7, 9, and 12).
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| 13.
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Somei, Masanori ; Noguchi, Koichi ; Yamada, Fumio
概要:
金沢大学大学院自然科学研究科生理活性物質科学<br />金沢大学薬学部<br />1-Hydroxyyohimbine was prepared for the first time. Its skeletal rearrangement
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reaction either directly into 2-oxindole or into 3-oxindole derivatives by a series of reaction is reported. 1-Hydroxyyohimbine and some of its derivatives showed potent α2 blocking activity.
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| 14.
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Nakai, Yu-ya ; Goto, Aya ; Yamada, Fumio ; Somei, Masanori
概要:
金沢大学大学院自然科学研究科生理活性物質科学<br />金沢大学薬学部<br />Syntheses of N-2-(1-hydroxyindol-3-yl)ethyl-1-hydroxyindole-3-acetamide (3a) an
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d -indole-3-acetamide (4a) are reported. They undergo nucleophilic substitution reaction at the 1-position upon reaction with indole in 85% formic acid to give new type compounds, N-2-[1-(indol-3-yl)indol-3-yl]ethylindole-3-acetamide (13), N-2-(indol-3-yl)ethyl-(14), and N-2-[1-(indol-3-yl)indol-3-yl]ethyl-1-(indol-3-yl)indole-3-acetamide (15).
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| 15.
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Hasegawa, Masakazu ; Nagahama, Yoshiyuki ; Kobayashi, Kensuke ; Hayashi, Masumi ; Somei, Masanori
概要:
金沢大学大学院自然科学研究科生理活性物質科学<br />金沢大学薬学部<br />Formations of 6-mesyloxytryptamines and 1-substituted 3a-(4- chlorobutoxy)-1,2,
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3,3a,8,8a-hexahydropyrrolo[2,3-b]indoles were newly found in the reactions of Nb-substituted 1-hydroxytryptamines with mesyl chloride in THF. The latter compounds suggest that the intermediate indol-3-yl cations can trap THF and cleave the ether bond..
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| 16.
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Yamada, Fumio ; Goto, Aya ; Somei, Masanori
概要:
金沢大学大学院自然科学研究科生理活性物質科学<br />金沢大学薬学部<br />A simple and convenient synthetic methodology for 3a-(indol-3-yl)- 1,2,3,3a,8,8
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a-hexahydropyrrolo[2,3-b]indole, the core structure of leptosins D-F is developed by applying nucleophilic substitution reaction of 1- hydroxytryptamines.
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| 17.
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Yamada, Koji ; Izumi, Tomoyuki ; Yamada, Fumio ; Somei, Masanori
概要:
金沢大学大学院自然科学研究科生理活性物質科学<br />金沢大学薬学部<br />1-Methoxy-3-(2-nitrovinyl)indole (1a) functions as an electrophile and reacts w
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ith various nucleophiles. In THF, nucleophiles undergo conjugate addition to the β-carbon of the nitroviyyl side chain of 1a, regioselectively. The resultant Michael addition products (4d and 8) cyclize to novel 3-substituted 1-methoxyindoles (5 and 7) depending on reaction conditions and a plausible mechanism is discussed. In dipolar aprotic solvent (DMF), nucleophiles react with 1a at the 2-position predominantly with concomitant liberation of the 1-methoxy group giving 2-substituted indoles. © 2005 The Japan Institute of Heterocyclic Chemistry.
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| 18.
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Yamada, Koji ; Tanaka, Yoshio ; Somei, Masanori
概要:
金沢大学医薬保健研究域薬学系<br />金沢大学名誉教授<br />Nb-Acyl- and Nb-acyl-1-hydroxytryptamines are found to be novel and structurally simpl
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e (α2-blocker for the treatment of erectile dysfunction. © 2009 The Japan Institute of Heterocyclic Chemistry All rights reserved.
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| 19.
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Somei, Masanori ; Noguchi, Koichi ; Yoshino, Katsumasa ; Mori, Koichiro ; Asada, Mamiko ; Yamada, Fumio ; Tanaka, Yoshio ; Shigenobu, Koki ; Koike, Katsuo
概要:
金沢大学大学院自然科学研究科生理活性物質科学<br />金沢大学薬学部
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| 20.
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染井, 正徳 ; 山田, 文夫 ; Somei, Masanori ; Yamada, Fumio
概要:
1.インドロ[2,3-a]カルバゾール化合物群の研究<br />(1)インドリンから1-ヒドロキシインドールを合成する新反応を見出し,1-メトキシインドールへ誘導後2位をリチウム化し酸化カップリングして,2,2'-ビインドリル(1)を得る新
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手法を開拓した。<br />(2)インジゴを還元して,1,3-アセトキシ-2,2'ミビインドリル(2),1-アセチル-2,3-ジヒドロ-2,2'-ビインドリル(3)をそれぞれ1工程で,選択的に作り分ける独自の新反応を3種類見い出した。<br />(3)1,2,3のそれぞれを出発原料として,抗菌,抗ガン作用を持つ天然物,6-シアノ-5-メトキシインドロ[2,3-a]カルバゾール(4)に適用可能な5種類の新規全合成法を見出した。<br />(4)4に至る合成中間体から,様々な4の誘導体の合成が可能となった。<br />(5)N-グリコシル-2,2'-ビインドリル(5)の簡単な合成法を開拓し,本基質から,N-グリコシルインドロ[2,3-a]カルバゾール化合物群を得る新手法を見出した。<br />(6)5位に酸素官能基を有するインドロ[2,3-a]カルバゾール化合物群の簡便な新しい一般合成法を確立した。<br />2.インドロ[2,3-a]カルバゾール化合物研究の発端となった1-ヒドロキシおよび1-メトキシインドール化学の展開<br />(1)1-ヒドロキシインドール類はこれまで未知であった求核置換反応を5位で位置選択的に起こすという新事実を発見することが出来た。<br />(2)1-ヒドロキシおよび1-メトキシインドール類は,その構造に基づく特徴的な新反応を数多く起こし,新反応,新事実の宝庫であることが分かった。<br />(3)これまで全くその存在も知られていなかった,インドールの化学における独創的な,全く新しい領域への扉を開くことが出来,今後の進展は末広がりの状態となっている。 1. Study toward Indolo [2,3-α] carbazoles<br /> Important building blocks such as 2,2'-biindolyl, 3-acetoxy-2,2'-biindolyl, 1-acetyl-2,3-dihydro-2,2'-biindolyl were prepared by our own new reactions from industrially available chemical, indigo. Utilizing these compounds as starting materials, four short step total synthetic routes to an antibiotic, 6-cyano-5-methoxyindolo [2,3-α] carbazole, were developed.<br /> N-Glycosyl 2,2'-biindolyls were also prepared and found to be excellent substrates for producing N-glycosylindolo [2,3-α] carbazoles.<br /> Above methods are widely applicable for the syntheses of various kinds of indolo [2,3-α] carbazoles.<br />2. The Chemistry of 1-Hydroxyindoles<br /> 2,2'-Biindolyl was also prepared through oxidative coupling of lithium 1-methoxyindol-2-yl and converted to indolo [2,3-α] carbazoles which constituted the fifth synthetic route.<br /> 1-Methoxyindoles are prepared from 1-hydroxyindoles, which are new compounds in indole chemistry. The chemistry of 1-hydroxyindoles was widely examined and found to be rich in a lot of new findings that were not expected from thusfar known indole chemistry.<br /> A frontier in indole chemistry is now open.<br />研究課題/領域番号:10470466, 研究期間(年度):1998–2000, 研究成果報告書の一部を掲載(pp.1-22:研究成果報告書の概要, 本研究の背景および成果についての概説, pp.46-50,pp.51-54:第23回および第25回 反応と合成の進歩シンポジウム―ライフサイエンスを志向した理論、反応及び合成―講演要旨集の抜粋, 主催:日本薬学会)<br />出典：「創薬を指向したインドロカルバゾールを共通骨格とする抗ガン性天然物の短工程合成研究」研究成果報告書 課題番号10470466 (KAKEN：科学研究費助成事業データベース（国立情報学研究所）) 本文データは著者版報告書より作成
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| 21.
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Somei, Masanori ; Iwaki, Takako ; Yamada, Fumio ; Tanaka, Yoshio ; Shigenobu, Koki ; Koike, Katsuo ; Suzuki, Nobuo ; Hattori, Atsuhiko
概要:
金沢大学大学院自然科学研究科生理活性物質科学<br />金沢大学薬学部<br />According to the definition of the ideal synthetic method, an example aimed at
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the leads for an α2 blocker, an inhibitor of platelet aggregation, and an anti-osteoporosis agent is established starting from tryptamine. The originality rate, the intellectual property, and the application potential factors of the method are 71, 54, and 100, respectively. The method employs only conventional reagents and reaction conditions without using any protecting groups.{A figure is presented}. © 2006 The Japan Institute of Heterocyclic Chemistry
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| 22.
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Somei, Masanori ; Noguchi, Koichi ; Yamagami, Ryutaro ; Kawada, Yumiko ; Yamada, Koji ; Yamada, Fumio
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金沢大学大学院自然科学研究科生理活性物質科学<br />金沢大学薬学部<br />Novel 9-hydroxy-β-carboline derivatives were produced for the first time. A nov
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el rearrangement reaction of 1, 2, 3, 4-tetrahydro-9-hydroxy-β-carbolines was discovered to give 3, 3-disubstituted oxindoles, which was successfully applied to the total synthesis of (±)-coerulescine.
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| 23.
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Somei, Masanori ; Yamada, Fumio ; Suzuki, Yoshiaki ; Ohmoto, Shinobu ; Hayashi, Hiroyuki
概要:
金沢大学大学院自然科学研究科生理活性物質科学<br />For evaluating the effectiveness of organic synthesis, both intellectual property factor (IP
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F) and application potential factor (APF) are proposed. As a representative example, a highly effective synthetic method with IPF value of 53.8 and APF value of 100 has been established starting from indigo directing toward an antibiotic, 6-cyano-5-methoxy-12-methylindolo[2,3-a]carbazole, using only conventional reagents without using any protecting groups. © 2004 The Japan Institute of Heterocyclic Chemistry All rights reserved.
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| 24.
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Yoshino, Katsumasa ; Yamada, Fumio ; Somei, Masanori
概要:
金沢大学医薬保健研究域薬学系<br />金沢大学名誉教授<br />X-Ray analyses of 1-hydroxyyohimbine derivatives clearly show the deviation of the N(1
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)-O bond from the indole molecular plane. This phenomenon supports our working hypothesis "bishomoallylic conjugation". The deviation is responsible for the unprecedented nucleophilic substitution reaction in 1-hydroxyindole chemistry and effected the synthesis of novel 7β-heteroarylyohimbine and 4aα-heteroaryl-1,2,3,4-tetrahydro-β-carboline derivatives from the corresponding 1-hydroxyindole derivatives. © 2008 The Japan Institute of Heterocyclic Chemistry All rights reserved.
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| 25.
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Yamada, Fumio ; Shinmyo, Daisuke ; Nakajou, Masahiro ; Somei, Masanori
概要:
1-Methoxyindole-3-carbaldehyde is proved to be a versatile electrophile and reacts regioselectively at the 2-position wi
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th various types of nucleophiles providing 2-substituted indole-3-carbaldehydes. © 2012 The Japan Institute of Heterocyclic Chemistry.
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| 26.
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Suzuki, Nobuo ; Somei, Masanori ; Kitamura, Keiichiro ; Reiter, Russel J. ; Hattori, Atsuhiko
概要:
金沢大学環日本海域環境研究センター生物多様性研究部門<br />The teleost scale is a calcified tissue that contains osteoclasts, osteoblasts, and bone
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matrix, all of which are similar to those found in mammalian membrane bone. Using the goldfish scale, we recently developed a new in vitro assay system and previously demonstrated that melatonin suppressed both osteoclastic and osteoblastic activities in this assay system. In mammals, 2-bromomelatonin possesses a higher affinity for the melatonin receptor than does melatonin. Using a newly developed synthetic method, we synthesized 2-bromomelatonin, 2,4,6-tribromomelatonin and novel bromomelatonin derivatives (1-allyl-2,4,6-tribromomelatonin, 1-propargyl-2,4,6-tribromomelatonin, 1-benzyl-2,4,6-tribromomelatonin, and 2,4,6,7-tetrabromomelatonin) and then examined the effects of these chemicals on osteoclasts and osteoblasts. All bromomelatonin derivatives, as well as melatonin, had an inhibitory action on osteoclasts. In particular, 1-benzyl-2,4,6-tribromomelatonin (benzyl-tribromomelatonin) possessed a stronger activity than melatonin. At an in vitro concentration of 10-10 m, benzyl-tribromomelatonin still suppressed osteoclastic activity after 6 hr of incubation. In reference to osteoblasts, all bromomelatonin derivatives had a stimulatory action, although melatonin inhibited osteoblastic activity. In addition, estrogen receptor mRNA expression (an osteoblastic marker) was increased in benzyl-tribromomelatonin (10-7 m)-treated scales. Taken together, the present results strongly suggest that these novel melatonin derivatives have significant potential for use as beneficial drug for bone diseases such as osteoporosis. © 2007 The Authors. 全文公開200904
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| 27.
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Yamada, Koji ; Yamada, Fumio ; Shiraishi, Takei ; Tomioka, Saori ; Somei, Masanori
概要:
金沢大学医薬保健研究域薬学系<br />金沢大学名誉教授
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| 28.
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Hayashi, Toshikatsu ; Nakai, Yu-ya ; Yamada, Fumio ; Somei, Masanori
概要:
金沢大学大学院自然科学研究科生理活性物質科学<br />金沢大学薬学部<br />A novel synthetic method is discovered for 3-hydroxy-3H-indole-3-ethanamines an
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d -3H-indole-3-acetamides having either a 4-morpholinyl or 1-pyrrolidinyl group at the 2-position by reacting the corresponding 1-hydroxyindoles with enamines in the presence of tosyl or mesyl chloride. A plausible mechanism is proposed.
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| 29.
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Iwaki, Takako ; Fujita, Yasuaki ; Yamada, Fumio ; Somei, Masanori
概要:
金沢大学大学院自然科学研究科生理活性物質科学<br />金沢大学薬学部<br />1-(β-D-Xylopyranosyl)- (2a), 1-(β-D-glucopyranosyl)- (2b), 1-(β-D-galactopyrano
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syl)- (2c), and 1-(α-D-arabinopyranosyl)melatonins (3b) are prepared as water-soluble melatonins starting from melatonin.
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| 30.
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Yamada, Koji ; Kawasaki, Toshiya ; Fujita, Tomomi ; Somei, Masanori
概要:
金沢大学大学院自然科学研究科生理活性物質科学<br />金沢大学薬学部<br />Nucleophilic substitution reaction of 1-methoxy-6-nitroindole (1) was examined.
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In the reaction with sodium methoxide or sodium cyanide as a nucleophile, 2- and 3-methoxy-6-nitroindoles, and 7-cyano-6-nitroindole were obtained, respectively. A novel methylene homologation at the 3-position was found in the reaction of 1 with sodium methyl sulfide or potassium salt of diethyl malonate to give 3-methylthiomethytyl-6-nitroindole and its 2-methylthio derivative, and diethyl 2-(6-nitroindol-3-yl)methylmalonate, respectively. Possible reaction mechanism is discussed.
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| 31.
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Yamada, Koji ; Teranishi, Sakiko ; Miyashita, Ayako ; Ishikura, Minoru ; Somei, Masanori
概要:
Utilizing novel Nb-substituted serotonins, 5-and/or 6-substituted 3,4,5,6-tetrahydro-7-hydroxy-1H-azepino[5,4,3-cd]indol
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e derivatives are produced simply by treating serotonins with aldehydes under basic conditions. Synthesis of 2,2a,3,4,5,6-hexahydro-7-hydroxy-1H-azepino[5,4,3-cd]indole-2-one derivatives is also reported. © 2011 The Japan Institute of Heterocyclic Chemistry.
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| 32.
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Suzuki, Nobuo ; Somei, Masanori ; Seki, Azusa ; Reiter, Russel J. ; Hattori, Atsuhiko
概要:
金沢大学環日本海域環境研究センター生物多様性研究部門<br />Several reports indicate that melatonin is involved in the regulation of bone metabolism
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. To examine the direct effect of melatonin on osteoclasts and osteoblasts, we developed an in vitro assay using fish scales that contain osteoclasts, osteoblasts, and bone matrix, all of which are similar to those found in mammalian membrane bone. Using the assay, we demonstrated that melatonin suppressed osteoclastic and osteoblastic activities. These findings are in agreement with the reports from in vivo studies in mice and rats. In an attempt to develop molecules that increase bone mass, novel bromomelatonin derivatives were synthesized, and the effects of these chemicals on osteoclasts and osteoblasts using the scale assay were examined. As a result, novel bromomelatonin derivatives with the ability to possibly increase bone formation were identified. In scale osteoclasts, particularly, 1-benzyl-2,4,6- tribromomelatonin had a more potent activity than melatonin. In reference to osteoblasts, this agent (10-9-10-6m) significantly activated osteoblasts. The effect of 1-benzyl-2,4,6-tribromomelatonin on bone formation was confirmed in ovariectomized rats. Thus, the oral administration of 1-benzyl-2,4,6-tribromomelatonin augmented the total bone mineral density of the femoral metaphysis of ovariectomized rats. The stress-strain index of the diaphysis in 1-benzyl-2,4,6-tribromomelatonin-treated rats significantly increased in comparison with that in ovariectomized rats. In rats fed a low-calcium diet, the total bone mineral density of the femoral metaphysis significantly increased following the oral administration of 1-benzyl-2,4,6-tribromomelatonin. These studies identified a melatonin derivative that may have potential use in the treatment of bone diseases, such as osteoporosis. © 2008 The Authors.
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| 33.
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Somei, Masanori ; Yamada, Fumio
概要:
A novel reductive amino-cyclization method for the synthesis of azacycloalkanes is developed. Its versatility is proved
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by the total syntheses of (±)-aurantioclavine (1), an ergot alkaloid, and (±)-lophocerine (2), a cactus alkaloid, as examples of azepane and piperidine skeletons, respectively. © 2007 The Japan Institute of Heterocyclic Chemistry.
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| 34.
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Yamada, Koji ; Yamada, Fumio ; Shiraishi, Takei ; Tomioka, Saori ; Somei, Masanori
概要:
金沢大学大学院自然科学研究科生理活性物質科学<br />金沢大学薬学部<br />1-Methoxy-6-nitroindole-3-carbaldehyde is proved to be a versatile substrate fo
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r the nucleophilic substitution reactions providing 2,3,6-trisubstituted indole derivatives. Preparation of a novel pyrimido[1,2-a]indole derivative is also reported.
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| 35.
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Somei, Masanori ; Sayama, Shinsuke ; Naka, Katsumi ; Shinmoto, Kotaro ; Yamada, Fumio
概要:
金沢大学医薬保健研究域薬学系<br />金沢大学名誉教授<br />Abstract - Various new 2-substituted indole-3-carbaldehydes are prepared. Structurally
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related alkaloids, vulcanine and borreline, are synthesized as well. Among the compounds, 2-haloindole-3-carbaldehydes are found to be potent promoters of plant's root growth. Its successful preliminary application is reported for making Gobi desert in Inner Mongolia full of plant. © 2007 The Japan Institute of Heterocyclic Chemistry.
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| 36.
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Yamada, Koji ; Yamada, Fumio ; Somei, Masanori
概要:
金沢大学大学院自然科学研究科生理活性物質科学<br />1-Hydroxytryptamine derivatives undergo nucleophilic substitution reaction on the indole nit
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rogen (Na) as a general reaction by the treatment with acid, providing a novel synthetic method for 1-aryltryptamines. Depending on the structures of nucleophiles, 5- and 7-substituted tryptamines can also be produced in addition to the 1-aryltryptamines.<br />An easy approach to 7-substituted 4,5-dihydro-7H-pyrano[3,4-c]-isoxazole derivatives (3a-b and 6a-d) is described by the reaction of 2-aryl substituted 1-nitro-3-oxa-6-heptynes (2, 5a and 5b) with n-BuLi, followed by treatment with acetic anhydride.
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| 37.
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Somei, Masanori
概要:
Various derivatives of indole-3-carbaldehyde are found to be root regulators and they are named SOMRE compounds. Since s
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ome of them are potent root promoters and make roots three times longer than usual, their possibilities for increasing food production, combating yellow sand and desertification in Gobi desert, China, were examined. All preliminary experiments are thus far working well. For greening desert and stopping the global warming, it is vital importance to sow seeds to vast area of sand dune all at once. We are now on the stage to scatter seeds, pretreated with SOMRE, to sand dune by airplane. © The Japan Institute of Heterocyclic Chemistry.
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| 38.
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Somei, Masanori ; Yamada, Fumio ; Kurauchi, Takashi ; Nagahama, Yoshiyuki ; Hasegawa, Masakazu ; Yamada, Koji ; Teranishi, Sakiko ; Sato, Haruhiko ; Kaneko, Chikara
概要:
Application of regioselective nucleophilic substitution reactions of 1-hydroxytryptamines to novel and simple syntheses of serotonin (1a), N-methylserotonin (1b), bufotenine (1c), 5-methoxy-N-methyltryptamine (2a),
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bufobutanoic acid (3a), N-(indol-3-yl)methyl-5-methoxy-N-methyltryptamine (4), and lespedamine (5) are described. Effective syntheses of 5-benzyloxytryptamine and 1-methoxy-2-oxindoles are also reported.
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| 39.
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染井, 正徳 ; 山田, 康司 ; 山田, 文夫 ; Somei, Masanori
概要:
We have opened the new door to the virgin territory of "the chemistry of 1-hydroxyindoles" and established it as an inte
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llectual property of Japan. In the course of extending the chemistry, we have developed various new findings and new reactions.1.Creation of 1-HydroxyindolesWe have given birth to various new 1-hydroxyindole compounds thus far unknown. Especially, 1-hydroxy-tryptophan and -tryptamine derivatives are important. They undergo nucleophilic substitution reactions on the indole nitrogen.2.Discovery of dimerization of 1-hydroxymelatonin.The reaction was applied successfully to make 3a,3a'-bispyrrolo[2,3-b]indole nucleus. This new reaction has been attempted to apply for the synthesis of biologically active calabar indole alkaloids, which are expected to be lead compounds for Altzheimer's diseases. The synthesis is now in the final stage.3.Nucleophilic substitution reactions on in dole nucleusThis unprecedented new reactions are discovered for the first time. Applying the reactions, various kinds of building blocks, including 2-substituted indoles, thus far hardly accessible by the conventional chemistry, become readily available.<br />世界で初めての1-ヒドロキシインドールの化学という、新規な学問領域を確立することに成功した我々は、活発にその展開研究を進展中であり、下記の成果を挙げた。日本発の独創的研究であり、昨年までの成果は、米欧、国内を問わず多数の他の研究者により利用されている。しかし、公正に我々を引用する研究者が、米欧には少ない、ということに驚いている。1.染井正徳分担:強力な抗がん作用を持ち,未だに合成されていないレプトシンアルカロイド合成のための、合目的的な新規反応を確立するために,新規な1-ヒドロキシトリプトファンの世界初の合成に成功した。本化合物の化学反応性を検討した結果、期待通り求核置換反応を起すという新事実を見出した。したがって、当初の目的達成のための基礎知見を確立できた。2.山田文夫分担:画期的な新反応(1-ヒドロキシメラトニンの二量化反応)を発見し、標的アルカロイドの母核である3a,3a'-ビスピロロ[2,3-b]インドール骨格を1工程で形成するための最適条件を発見できた。得られたモデル基質を用いて、種々反応を試み、各種誘導体群の合成が可能であることを確認できた。さらに、分子内のメトキシ基の除去による天然物合成を試み、最終段階に到達した。3.山田康司分担:1-ヒドロキシインドール化合物群の求電子置換反応を継続し、臭素化における新しい事実を多数発見することに成功した。また、6- ニトロ- 1-ヒドロキシインドール-3- カルバルデヒドと、各種の求核試薬との反応を検討し、本化合物が例外なく、2位で高収率、高位置選択的に求核置換反応を起こすことを確認でき、従来法では合成困難であったタイプの2位置換インドール化合物群を容易に手中に出来る方法論の確立に成功した。以上の成果は、日本オリジンの知的財産であるとともに、末広がりの予測される、新しいインドール研究分野の扉が開かれたことを意味している。<br />研究課題/領域番号:15590002, 研究期間(年度):2003–2004, 研究成果報告書の一部を掲載(pp.1-6:研究成果報告書の概要, 本研究の背景および成果についての概説, pp.7-9:日本薬学会北陸支部例会・日本病院薬剤師会北陸ブロック学術大会講演要旨の抜粋, pp.141-145,pp.146-150:第33回および第34回複素環化学討論会講演要旨集の抜粋, pp.151-153,pp.154-156:第29回および第30回反応と合成の進歩シンポジウム―ライフサイエンスを志向した理論、反応及び合成―講演要旨集の抜粋, 主催:日本薬学会)<br />出典：「生理活性インドールアルカロイドの共通全合成法の開拓と独自のリードの創造研究」研究成果報告書 課題番号15590002 (KAKEN：科学研究費助成事業データベース（国立情報学研究所）) 本文データは著者版報告書より作成
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| 40.
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Yamada, Fumio ; Goto, Aya ; Peng, Wu ; Hayashi, Toshikatsu ; Saga, Yoshitomo ; Somei, Masanori
概要:
金沢大学大学院自然科学研究科生理活性物質科学<br />金沢大学薬学部<br />A novel nucleophilic substitution reaction at the 1-position of indole nucleus
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was discovered by reacting 1-hydroxytryptamine and -tryptophan derivatives with indoles in 85% formic acid yielding 1-(indol-3-yl)indoles. Their structures were determined by X-Ray crystallographic analysis and chemical correlations. An SN2 mechanism on the indole nitrogen (1-position) is proposed.
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| 41.
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Yamada, Koji ; Kanbayashi, Yukiko ; Tomioka, Saori ; Somei, Masanori
概要:
金沢大学大学院自然科学研究科生理活性物質科学<br />金沢大学薬学部<br />Syntheses of wasabi phytoalexin analogs, such as 6-bromo-5-iodo, 2-bromo-5-iodo
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, 6-nitro, 5-chloroacetyl, and 6-chloroacetyl congeners, are reported. An interesting effect of the 1-methoxy group on the regioselectivity of electrophilic substitution reactions on indole nucleus is observed.
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| 42.
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Somei, Masanori ; Tanimoto, Asuka ; Orita, Hitomi ; Yamada, Fumio ; Ohta, Toshiharu
概要:
金沢大学大学院自然科学研究科生理活性物質科学<br />金沢大学薬学部<br />A simple synthetic method for methyl 1-methoxyindole-3-carboxylate, a phytoalex
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in isolated from Wasabia japonica, syn. Eutrema wasabi, and its 5-iodo derivative is reported. They underwent nucleophilic substitution reactions selectively at the 2-position.
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| 43.
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Yamada, Fumio ; Hayashi, Toshikatsu ; Yamada, Koji ; Somei, Masanori
概要:
金沢大学大学院自然科学研究科生理活性物質科学<br />金沢大学薬学部<br />A lithium hydroxide promoted glucosidation of 1-hydroxyindoles with 2, 3, 4, 6-
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tetra-0-acetyl-α-D-glucopyranosyl bromide is newly developed. Applying this method, the first and simple syntheses of novel indol-1-yl glucosides were achieved.
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| 44.
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Somei, Masanori ; Yamada, Fumio
概要:
金沢大学大学院自然科学研究科生理活性物質科学<br />金沢大学薬学部<br />A lithium hydroxide promoted simple glycosylation of 4-hydroxyindole-3- acetoni
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trile with 2,3,4, 6-tetra-O-acetyl-a-D-glucopyranosyl bromide was developed. Utilizing the method, the first and five steps total synthesis of cappariloside A was achieved from indole-3-carbaldehyde in 41% overall yield.
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| 45.
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Somei, Masanori ; Yamada, Fumio ; Hayashi, Toshikatsu ; Goto, Aya ; Saga, Yoshitomo
概要:
金沢大学大学院自然科学研究科生理活性物質科学<br />金沢大学薬学部<br />1-(Indol-3-yl)indoles are obtained in excellent to good yields by the reaction
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of 1-hydroxyindoles with indole in 85% formic acid. Their structures are determined by X-Ray crystallographic analysis and chemical correlations. The unprecidented SN2 mechanism on the indole nitrogen is proposed.
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| 46.
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Yamada, Fumio ; Yamada, Koji ; Takeda, Hikari ; Somei, Masanori
概要:
金沢大学大学院自然科学研究科生理活性物質科学<br />金沢大学薬学部<br />Preparations of 5-nitroindol-1-yl (5a), 6-nitroindol-1-yl (5b), and 1,2,3-benzo
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triazol-1-yl 1-methoxyindole-3-carboxylates (9) are reported. These are active esters and proved to be useful intermediates for the preparations of ester and amide analogs of methyl 1-methoxyindole-3-carboxylate, a wasabi phytoalexin.
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| 47.
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Yamada, Fumio ; Somei, Masanori
概要:
金沢大学医薬保健研究域薬学系<br />金沢大学名誉教授<br />A novel reductive amino-cyclization method for the synthesis of azacycloalkanes is dev
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eloped. Its versatility is proved by the total syntheses of (±)-aurantioclavine (1), an ergot alkaloid, and (±)-lophocerine (2), a cactus alkaloid, as examples of azepane and piperidine skeletons, respectively. © 2007 The Japan Institute of Heterocyclic Chemistry.
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| 48.
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Somei, Masanori
概要:
金沢大学医薬保健研究域薬学系<br />金沢大学名誉教授<br />This review reports how the author has been realizing his synthetic philosophy and fiv
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e dreams as his life work. The philosophy consists of such three elements as originality rate, intellectual property factor, and application potential factor. On the basis of these elements, an ideal and an efficient synthesis are defined. In the study for the total synthesis of ergot alkaloids, the first concrete example of an approximately ideal synthesis was demonstrated. Further examples are shown relying on the chemistry of 1-hydroxyindoles. A lot of intellectual properties created by the author are successfully condensed to provide promising lead compounds meeting for the respective dreams of developing five drugs 1) for making desert green and food increase in production, 2) for cardiovascular system disease, 3) for dementia, 4) for lifestyle-related disease (osteoporosis, etc.), and 5) for cancer and virus. With potent promoters of plant's root growth in hand, the first dream is going now successfully. Preliminary experiments combating desertification at Gobi desert in Inner Mongolia are reported in detail, aiming for preventing global warming. © 2008 The Japan Institute of Heterocyclic Chemistry.
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