最終更新日2017年02月01日

氏名

ヤマグチ ジュンイチロウ

山口 潤一郎

職名

准教授 准教授

所属理工学術院

(先進理工学部)

連絡先

メールアドレス

メールアドレス
junyamaguchi@waseda.jp

本属以外の学内所属

兼担

理工学術院(大学院先進理工学研究科)

学歴・学位

学歴

1997年04月-2002年03月 東京理科大学 工学部 工業化学科
2002年04月-2007年03月 東京理科大学大学院 工学研究科 工業化学専攻

学位

博士(工学) 東京理科大学

経歴

2004年04月-2007年03月日本学術振興会特別研究員(DC1)
2007年04月-2008年07月日本学術振興会海外特別研究員(海外PD)
2008年08月-2012年03月名古屋大学理学研究科助教
2012年04月-2016年03月名古屋大学理学研究科准教授
2016年04月-早稲田大学理工学術院准教授

所属学協会

日本化学会

アメリカ化学会

有機合成化学協会

近畿化学協会

ケミカルバイオロジー学会

プロセス化学会

委員歴・役員歴(学外)

2013年04月-2014年03月日本化学会東海支部
2014年04月-2015年03月日本化学会東海支部
2015年03月-2016年03月有機合成化学協会
2016年04月-2018年03月有機合成化学協会
2016年04月-日本化学会
2016年04月-日本化学会

受賞

小玉科学賞

2004年03月授与機関:科学技術振興会

日本化学会学生講演賞

2006年03月授与機関:日本化学会

有機合成化学協会研究企画賞

2009年02月授与機関:有機合成化学協会

天然物化学談話会奨励賞

2011年09月授与機関:天然物化学談話会

日本化学会若い世代の講演証

2012年03月授与機関:日本化学会

日本化学会進歩賞

2013年03月授与機関:日本化学会

化学コミュニケーション賞

2013年03月授与機関:日本化学連合

ITbM Research Award

2013年10月授与機関:名古屋トランスフォーマティブ生命分子研究所

Banyu Chemist Awarad 2013

2013年11月授与機関:Merck

Thieme Chemistry Jornal Award 2014

2014年01月授与機関:Thieme

Asian Core Lectureship Award, China

2014年12月授与機関:ACP

Asian Core Lectureship Award, Thailand

2014年12月授与機関:ACP

文部科学大臣若手科学者賞

2017年04月授与機関:MEXT

アジア化学連合(FACS)ディスティングィッシュ若手化学者賞

2017年07月授与機関:FACS

取材ガイド

専門分野
有機合成化学、有機金属化学、ケミカルバイオロジー

研究分野

キーワード

有機化学、有機合成化学

研究テーマ履歴

2016年04月-2018年03月多様な複雑チオペプチド抗生物質の高効率合成
2016年04月-2019年03月結合切断反応が拓く革新的分子合成技術の開発
2016年04月-2018年03月環拡大反応を利用したフシコクシンAの全合成研究
2016年04月-2018年03月芳香族カルボン酸誘導体をカップリング剤とした高難度変換反応の開発

論文

Cyanation of Phenol Derivatives with Aminoacetonitriles by Nickel Catalysis

Takise, Ryosuke;Itami, Kenichiro;Yamaguchi, Junichiro

ORGANIC LETTERS18(17)p.4428 - 44312016年-2016年

DOIWoS

詳細

ISSN:1523-7060

Palladium-Catalyzed Decarbonylative Cross-Coupling of Azinecarboxylates with Arylboronic Acids

Muto, Kei;Hatakeyama, Taito;Itami, Kenichiro;Yamaguchi, Junichiro

ORGANIC LETTERS18(19)p.5106 - 51092016年-2016年

DOIWoS

詳細

ISSN:1523-7060

Palladium-catalyzed Decarbonylative Alkynylation of Aromatic Esters

Okita Toshimasa;Kumazawa Kazushi;Takise Ryosuke;Muto Kei;Itami Kenichiro;Yamaguchi Junichiro

Chemistry Letters46(2)p.218 - 2202017年-2017年

CiNii

詳細

概要:

A palladium-catalyzed decarbonylative alkynylation reaction of aromatic esters with terminal alkynes is reported. This reaction allows for halogen-free Sonogashira coupling, resulting in various aryl- and heteroarylalkynes. The utility of the reaction was demonstrated by orthogonal coupling reaction.

Nickel-Catalyzed Aromatic C–H Functionalization

Yamaguchi, Junichiro; Muto, Kei; Itami, Kenichiro; Itami, Kenichiro

Topics in Current Chemistry374(4)2016年08月-2016年08月 

DOIScopus

詳細

ISSN:03401022

概要:© 2016, Springer International Publishing Switzerland.Catalytic C–H functionalization using transition metals has received significant interest from organic chemists because it provides a new strategy to construct carbon–carbon bonds and carbon–heteroatom bonds in highly functionalized, complex molecules without pre-functionalization. Recently, inexpensive catalysts based on transition metals such as copper, iron, cobalt, and nickel have seen more use in the laboratory. This review describes recent progress in nickel-catalyzed aromatic C–H functionalization reactions classified by reaction types and reaction partners. Furthermore, some reaction mechanisms are described and cutting-edge syntheses of natural products and pharmaceuticals using nickel-catalyzed aromatic C–H functionalization are presented.

Syntheses of Biologically Active 2-Arylcyclopropylamines

Miyamura, Shin; Itami, Kenichiro; Itami, Kenichiro; Itami, Kenichiro; Yamaguchi, Junichiro

Synthesis (Germany)49(6)p.1131 - 11492017年03月-2017年03月 

DOIScopus

詳細

ISSN:00397881

概要:© 2017 Georg Thieme Verlag Stuttgart. New York.The 2-arylcyclopropylamine (ACPA) motif is often seen in biologically active compounds. This review focuses on the synthesis of biologically active ACPAs and categorizes, by reaction type, the synthetic methods used toward such compounds. 1 Introduction 2 Cyclopropanation Using Diazo Compounds 2.1 Styrene 2.2 Cinnamate 2.3 Vinyl Phthalimide 2.4 Vinyl Acetamide 2.5 Oxazolone 2.6 Diketopiperazine 3 Cyclopropanation Using Ylides 3.1 Cinnamate 3.2 Nitrostyrene 3.3 Oxirane 3.4 Nitroacetate 4 Transformation of Cyclopropanes 4.1 Iodocyclopropane 4.2 Aminocyclopropane 5 Miscellaneous Methods 5.1 Kulinkovich Reaction 5.2 Three-Component Reaction 5.3 Intramolecular Nucleophilic Cyclization 5.4 Intramolecular Mitsunobu Reaction 5.5 Rearrangement from Cyclobutanone 6 Summary.

Decarbonylative Diaryl Ether Synthesis by Pd and Ni Catalysis

Takise, Ryosuke; Isshiki, Ryota; Muto, Kei; Itami, Kenichiro; Itami, Kenichiro; Yamaguchi, Junichiro

Journal of the American Chemical Society139(9)p.3340 - 33432017年03月-2017年03月 

DOIScopus

詳細

ISSN:00027863

概要:© 2017 American Chemical Society.Because diaryl ethers are present as an important motif in pharmaceuticals and natural products, extensive studies for the development of novel methods have been conducted. A conventional method for the construction of the diaryl ether moiety is the intermolecular cross-coupling reaction of aryl halides and phenols with a copper or palladium catalyst. We developed a catalytic decarbonylative etherification of aromatic esters using a palladium or nickel catalyst with our enabling diphosphine ligand to give the corresponding diaryl ethers. The present reaction can be conducted on gram scale in excellent yield. This reaction not only functions in an intramolecular setting but also allows for a cross-etherification using other phenols.

Synthesis of multiply arylated pyridines

Asako, Takashi; Hayashi, Wakana; Amaike, Kazuma; Suzuki, Shin; Itami, Kenichiro; Itami, Kenichiro; Muto, Kei; Yamaguchi, Junichiro

Tetrahedron2017年01月-2017年01月 

DOIScopus

詳細

ISSN:00404020

概要:© 2017 Elsevier Ltd.We have achieved a synthesis of multiply arylated pyridines by using a [4 + 2] cycloaddition of 2,4-diaryl-5-chloroxazoles and cinnamic acids as a key reaction. The resulting hydroxytriarylpyridines can be derivatized into triarylpyridines, tetraarylpyridines and pentaarylpyridines by sequential cross-couplings. This synthetic method allows for facile and rapid access to highly arylated pyridines with different aryl substituents.

Theoretical Elucidation of Potential Enantioselectivity in a Pd-Catalyzed Aromatic C-H Coupling Reaction

Nishimoto, Yoshio; Nishimoto, Yoshio; Nishimoto, Yoshio; Kondo, Hiroki; Yamaguchi, Kazuya; Yokogawa, Daisuke; Yokogawa, Daisuke; Yamaguchi, Junichiro; Yamaguchi, Junichiro; Yamaguchi, Junichiro; Itami, Kenichiro; Itami, Kenichiro; Itami, Kenichiro; Irle, Stephan; Irle, Stephan

Journal of Organic Chemistry82(9)p.4900 - 49062017年05月-2017年05月 

DOIScopus

詳細

ISSN:00223263

概要:© 2017 American Chemical Society.The mechanism of an aromatic C-H coupling reaction between heteroarenes and arylboronic acids using a Pd catalyst was theoretically and experimentally investigated. We identified the C-B transmetalation as the rate-determining step. The (S)-catalyst-reactant complex was found to be stabilized by hyperconjugation between π-orbitals on the tolyl group and the S-O σ* antibonding orbital in the catalyst ligand. Our findings suggest routes for the design of new, improved Pd catalysts with higher stereoselectivity.

Synthesis of fully arylated (hetero)arenes

Suzuki, Shin; Yamaguchi, Junichiro

Chemical Communications53(10)p.1568 - 15822017年01月-2017年01月 

DOIScopus

詳細

ISSN:13597345

概要:© The Royal Society of Chemistry.Multiply arylated arenes are privileged structures with highly useful functions and fascinating optoelectronic and biological properties. This feature article reports the synthesis of fully arylated (hetero)arenes bearing more than two different aryl substituents and categorizes this emerging topic by the type of (hetero)arene core and the type of chemistry employed to install the (hetero)aryl substituents.

C-H activation enables a rapid structure-activity relationship study of arylcyclopropyl amines for potent and selective LSD1 inhibitors

Miyamura, Shin; Araki, Misaho; Ota, Yosuke; Itoh, Yukihiro; Yasuda, Shusuke; Masuda, Mitsuharu; Taniguchi, Tomoyuki; Sowa, Yoshihiro; Sakai, Toshiyuki; Sakai, Toshiyuki; Suzuki, Takayoshi; Suzuki, Takayoshi; Itami, Kenichiro; Itami, Kenichiro; Yamaguchi, Junichiro

Organic and Biomolecular Chemistry14(36)p.8576 - 85852016年01月-2016年01月 

DOIScopus

詳細

ISSN:14770520

概要:© 2016 The Royal Society of Chemistry.We describe the structure-activity relationship of various arylcyclopropylamines (ACPAs), which are potent LSD1 inhibitors. More than 45 ACPAs were synthesized rapidly by an unconventional method that we have recently developed, consisting of a C-H borylation and cross-coupling sequence starting from cyclopropylamine. We also generated NCD38 derivatives, which are known as LSD1 selective inhibitors, and discovered a more effective inhibitor compared to the original NCD38.

The AMOR Arabinogalactan Sugar Chain Induces Pollen-Tube Competency to Respond to Ovular Guidance

Mizukami A.G., Inatsugi R., Jiao J., Kotake T., Kuwata K., Ootani K., Okuda S., Sankaranarayanan S., Sato Y., Maruyama D., Iwai H., Garénaux E., Sato C., Kitajima K., Tsumuraya Y., Mori H., Yamaguchi J., Itami K., Sasaki N., Higashiyama T.

Current Biology26(8)p.1091 - 10972016年-

DOIScopus

詳細

ISSN:9609822

概要:Precise directional control of pollen-tube growth by pistil tissue is critical for successful fertilization of flowering plants [1-3]. Ovular attractant peptides, which are secreted from two synergid cells on the side of the egg cell, have been identified [4-6]. Emerging evidence suggests that the ovular directional cue is not sufficient for successful guidance but that competency control by the pistil is critical for the response of pollen tubes to the attraction signal [1, 3, 7]. However, the female molecule for this competency induction has not been reported. Here we report that ovular methyl-glucuronosyl arabinogalactan (AMOR) induces competency of the pollen tube to respond to ovular attractant LURE peptides in Torenia fournieri. We developed a method for assaying the response capability of a pollen tube by micromanipulating an ovule. Using this method, we showed that pollen tubes growing through a cut style acquired a response capability in the medium by receiving a sufficient amount of a factor derived from mature ovules of Torenia. This factor, named AMOR, was identified as an arabinogalactan polysaccharide, the terminal 4-O-methyl-glucuronosyl residue of which was necessary for its activity. Moreover, a chemically synthesized disaccharide, the β isomer of methyl-glucuronosyl galactose (4-Me-GlcA-β-(1→6)-Gal), showed AMOR activity. No specific sugar-chain structure of plant extracellular matrix has been identified as a bioactive molecule involved in intercellular communication. We suggest that the AMOR sugar chain in the ovary renders the pollen tube competent to the chemotropic response prior to final guidance by LURE peptides. © 2016 Elsevier Ltd. All rights reserved.

Synthesis of Triarylpyridines in Thiopeptide Antibiotics by Using a C-H Arylation/Ring-Transformation Strategy

Amaike K., Itami K., Yamaguchi J.

Chemistry - A European Journal22(13)p.4384 - 43882016年-

DOIScopus

詳細

ISSN:9476539

概要:We have described a C-H arylation/ring-transformation strategy for the synthesis of triarylpyridines, which form the core structure of thiopeptide antibiotics. This synthetic method readily gave 2,3,6-triarylpyridines in a regioselective manner by a two-phase approach: C-H arylation (a nickel-catalyzed decarbonylative Suzuki-Miyaura cross-coupling and decarbonylative C-H coupling for the synthesis of 2,4-diaryloxazoles) and ring transformation ([4+2] cycloaddition of 2,4-diaryloxazoles with (hetero)arylacrylic acids). To showcase these methods, we have accomplished the formal synthesis of thiopeptide antibiotics GE2270 s and amythiamicins. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Microwave-assisted regioselective direct C-H arylation of thiazole derivatives leading to increased σ1 receptor affinity

Kokornaczyk A., Schepmann D., Yamaguchi J., Itami K., Wünsch B.

MedChemComm7(2)p.327 - 3312016年-

DOIScopus

詳細

ISSN:20402503

概要:New thiazole analogues 2 of spirocyclic thiophenes 1, which are known to show high σ1 receptor affinities, have been developed as potentially better σ1 receptor ligands. To introduce an aryl group onto the thiazole core of 2 (C4 or C5 positions), we used Pd-catalyzed regioselective C-H arylation reactions. The Pd-catalyzed C5 arylation of 2a could be considerably improved by using microwave irradiation technique. The Pd-catalyzed C4 arylation of thiazole 2a with arylboronic acid 6 could be achieved in the presence of Pd(OAc)2, 1,10-phenanthroline, TEMPO, and LiBF4. Under these conditions, the tertiary amine and the tertiary alcohol were well-tolerated. The regioselective arylation of 2a led to new compounds 2b and 2c, with a 4-tolyl moiety in the C5- and C4-positions, displaying five to nine-fold increased σ1 affinity. The same σ1 affinity of the regioisomeric thiazoles 2b and 2c can be explained by fast rotation around the piperidine-thiazole bond. Compared to spirocyclic thiophenes 1, thiazoles 2 are considerably more polar. © The Royal Society of Chemistry 2016.

Synthesis of Natural Products and Pharmaceuticals via Catalytic C-H Functionalization

Yamaguchi J., Amaike K., Itami K.

Transition Metal-Catalyzed Heterocycle Synthesis via C-H Activationp.505 - 5502016年-

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概要:The synthesis of natural products and pharmaceuticals, particularly those containing heterocyclic frameworks, can be dramatically simplified by using catalytic C-H functionalization. C-H functionalization has gathered significant interest from the organic synthesis community because it provides a new strategy to construct carbon-carbon and carbon-heteroatom bonds in highly functionalized, complex molecules without prefunctionalization. In this book chapter, methods in heterocycle substitution and synthesis using catalytic C-H functionalization are classified by heterocycle, with specific focus on the cutting-edge synthesis of natural products and pharmaceuticals. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA. All rights reserved.

C-H activation enables a rapid structure-activity relationship study of arylcyclopropyl amines for potent and selective LSD1 inhibitors

Miyamura S., Araki M., Ota Y., Itoh Y., Yasuda S., Masuda M., Taniguchi T., Sowa Y., Sakai T., Suzuki T., Itami K., Yamaguchi J.

Organic and Biomolecular Chemistry14(36)p.8576 - 85852016年-

DOIScopus

詳細

ISSN:14770520

概要:We describe the structure-activity relationship of various arylcyclopropylamines (ACPAs), which are potent LSD1 inhibitors. More than 45 ACPAs were synthesized rapidly by an unconventional method that we have recently developed, consisting of a C-H borylation and cross-coupling sequence starting from cyclopropylamine. We also generated NCD38 derivatives, which are known as LSD1 selective inhibitors, and discovered a more effective inhibitor compared to the original NCD38. © 2016 The Royal Society of Chemistry.

Decarbonylative organoboron cross-coupling of esters by nickel catalysis

Muto K., Yamaguchi J., Musaev D.G., Itami K.

Nature Communications62015年-

DOIScopus

詳細

ISSN:20411723

概要:The Suzuki-Miyaura cross-coupling is a metal-catalysed reaction in which boron-based nucleophiles and halide-based electrophiles are reacted to form a single molecule. This is one of the most reliable tools in synthetic chemistry, and is extensively used in the synthesis of pharmaceuticals, agrochemicals and organic materials. Herein, we report a significant advance in the choice of electrophilic coupling partner in this reaction. With a user-friendly and inexpensive nickel catalyst, a range of phenyl esters of aromatic, heteroaromatic and aliphatic carboxylic acids react with boronic acids in a decarbonylative manner. Overall, phenyl ester moieties function as leaving groups. Theoretical calculations uncovered key mechanistic features of this unusual decarbonylative coupling. Since extraordinary numbers of ester-containing molecules are available both commercially and synthetically, this new a € estera € cross-coupling should find significant use in synthetic chemistry as an alternative to the standard halide-based Suzuki-Miyaura coupling.

C-H activation generates period-shortening molecules that target cryptochrome in the mammalian circadian clock

Oshima T., Yamanaka I., Kumar A., Yamaguchi J., Nishiwaki-Ohkawa T., Muto K., Kawamura R., Hirota T., Yagita K., Irle S., Kay S.A., Yoshimura T., Itami K.

Angewandte Chemie - International Edition54(24)p.7193 - 71972015年-

DOIScopus

詳細

ISSN:14337851

概要:The synthesis and functional analysis of KL001 derivatives, which are modulators of the mammalian circadian clock, are described. By using cutting-edge CH activation chemistry, a focused library of KL001 derivatives was rapidly constructed, which enabled the identification of the critical sites on KL001 derivatives that induce a rhythm-changing activity along with the components that trigger opposite modes of action. The first period-shortening molecules that target the cryptochrome (CRY) were thus discovered. Detailed studies on the effects of these compounds on CRY stability implicate the existence of an as yet undiscovered regulatory mechanism. A change in rhythm: The first functional analysis of KL001 derivatives, which are mammalian circadian-clock modulators, was enabled by cutting-edge CH activation. The sites of the KL001 derivatives that are critical for their rhythm-changing activity were elucidated, which led to the discovery of the first period-shortening molecules that target the cryptochrome. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Concise syntheses of dictyodendrins A and F by a sequential C-H functionalization strategy

Yamaguchi A.D., Chepiga K.M., Yamaguchi J., Itami K., Davies H.M.L.

Journal of the American Chemical Society137(2)p.644 - 6472015年-

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ISSN:27863

概要:Syntheses of dictyodendrins A and F have been achieved using a sequential C-H functionalization strategy. The N-alkylpyrrole core is fully functionalized by means of a rhodium(I)-catalyzed C-H arylation at the C3-position, a rhodium(II)-catalyzed double C-H insertion at the C2- and C5-positions, and a Suzuki-Miyaura cross-coupling reaction at the C4-position. The syntheses of dictyodendrins A and F were completed by formal 6π-electrocyclization to generate the pyrrolo[2,3-c]carbazole core of the natural products. © 2015 American Chemical Society.

Ni-Catalyzed α-arylation of esters and amides with phenol derivatives

Koch E., Takise R., Studer A., Yamaguchi J., Itami K.

Chemical Communications51(5)p.855 - 8572015年-

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ISSN:13597345

概要:A nickel-catalyzed α-arylation of esters and amides with phenol derivatives has been accomplished. In the presence of our unique nickel catalyst, prepared in situ from Ni(cod)2, 3,4-bis(dicyclohexylphosphino)thiophene (dcypt), and K3PO4, various esters and amides undergo α-arylation with O-arylpivalates or O-arylcarbamates to afford the corresponding coupling products. The thus obtained α-aryl esters and amides are useful precursors of privileged motifs such as α-arylcarboxylic acids and β-arylamines. This journal is © The Royal Society of Chemistry.

Stereodivergent synthesis of arylcyclopropylamines by sequential C-H borylation and Suzuki-Miyaura coupling

Miyamura S., Araki M., Suzuki T., Yamaguchi J., Itami K.

Angewandte Chemie - International Edition54(3)p.846 - 8512015年-

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ISSN:14337851

概要:A step-economical and stereodivergent synthesis of privileged 2-arylcyclopropylamines (ACPAs) through a C-(sp3)-H borylation and Suzuki-Miyaura coupling sequence has been developed. The iridium-catalyzed C-H borylation of N-cyclopropylpivalamide proceeds with cis selectivity. The subsequent B-cyclopropyl Suzuki-Miyaura coupling catalyzed by [PdCl2(dppf)]/Ag2O proceeds with retention of configuration at the carbon center bearing the Bpin group, while epimerization at the nitrogen-bound carbon atoms of both the starting materials and products is observed under the reaction conditions. This epimerization is, however, suppressed in the presence of O2. The present new ACPA synthesis results in not only a significant reduction in the steps required for making ACPA derivatives, but also the ability to access either isomer (cis or trans) by simply changing the atmosphere (N2 or O2) in the coupling stage. © 2015 Wiley-VCH Verlag GmbH & Co. KGaA.

Synthesis and characterization of hexaarylbenzenes with five or six different substituents enabled by programmed synthesis

Suzuki S., Segawa Y., Itami K., Yamaguchi J.

Nature Chemistry7(3)p.227 - 2332015年-

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ISSN:17554330

概要:Since its discovery in 1825, benzene has served as one of the most used and indispensable building blocks of chemical compounds, ranging from pharmaceuticals and agrochemicals to plastics and those used in organic electronic devices. Benzene has six hydrogen atoms that can each be replaced by different substituents, which means that the structural diversity of benzene derivatives is intrinsically extraordinary. The number of possible substituted benzenes from n different substituents is (2n + 2n2 + 4n3 + 3n4 + n6)/12. However, owing to a lack of general synthetic methods for making multisubstituted benzenes, this potentially huge structural diversity has not been fully exploited. Here, we describe a programmed synthesis of hexaarylbenzenes using C-H activation, cross-coupling and [4+2] cycloaddition reactions. The present method allows for the isolation and structure-property characterization of hexaarylbenzenes with distinctive aryl substituents at all positions for the first time. Moreover, the established protocol can be applied to the synthesis of tetraarylnaphthalenes and pentaarylpyridines. © 2015 Macmillan Publishers Limited.

C-H arylation and alkenylation of imidazoles by nickel catalysis: Solvent-accelerated imidazole C-H activation

Muto K., Hatakeyama T., Yamaguchi J., Itami K.

Chemical Science6(12)p.6792 - 67982015年-

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ISSN:20416520

概要:The first nickel-catalyzed C-H arylations and alkenylations of imidazoles with phenol and enol derivatives are described. Under the influence of Ni(OTf)2/dcype/K3PO4 (dcype: 1,2-bis(dicyclohexylphosphino)ethane) in t-amyl alcohol, imidazoles can undergo C-H arylation with phenol derivatives. The C-H arylation of imidazoles with chloroarenes as well as that of thiazoles and oxazoles with phenol derivatives can also be achieved with this catalytic system. By changing the ligand to dcypt (3,4-bis(dicyclohexylphosphino)thiophene), enol derivatives could also be employed as coupling partners achieving the C-H alkenylation of imidazoles as well as thiazoles and oxazoles. Thus, a range of C2-arylated and alkenylated azoles can be synthesized using this newly developed nickel-based catalytic system. The key to the success of the C-H coupling of imidazoles is the use of a tertiary alcohol as solvent. This also allows the use of an air-stable nickel(ii) salt as the catalyst precursor. © 2015 The Royal Society of Chemistry.

Synthesis, binding affinity and structure-activity relationships of novel, selective and dual targeting CCR2 and CCR5 receptor antagonists

Junker A., Kokornaczyk A.K., Zweemer A.J.M., Frehland B., Schepmann D., Yamaguchi J., Itami K., Faust A., Hermann S., Wagner S., Schäfers M., Koch M., Weiss C., Heitman L.H., Kopka K., Wünsch B.

Organic and Biomolecular Chemistry13(8)p.2407 - 24222015年-

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ISSN:14770520

概要:CCR2 and CCR5 receptors play a key role in the development and progression of several inflammatory, cardiovascular and autoimmune diseases. Therefore, dual targeting of both receptors appeals as a promising strategy for the treatment of such complex, multifactorial disorders. Herein we report on the design, synthesis and biological evaluation of benzo[7]annulene- and [7]annulenothiophene-based selective and dual CCR2 and CCR5 receptor antagonists. Intermediates were designed in such a way that diversification could be introduced at the end of the synthesis. Starting from the lead compound TAK-779 (1), the quaternary ammonium moiety was exchanged by different non-charged moieties, the 4-methylphenyl moiety was extensively modified and the benzo[7]annulene core was replaced bioisosterically by the [7]annulenothiophene system. The naphthyl derivative 9h represents the most promising dual antagonist (Ki (CCR2) = 25 nM, IC50 (CCR5) = 17 nM), whereas the 6-isopropoxy-3-pyridyl and 4-methoxycarbonylphenyl derivatives 9k and 9r show more than 20-fold selectivity for the CCR2 (Ki = 19 nM) over the CCR5 receptor. This journal is © The Royal Society of Chemistry 2015.

C-H Activation Generates Period-Shortening Molecules That Target Cryptochrome in the Mammalian Circadian Clock

Oshima T., Yamanaka I., Kumar A., Yamaguchi J., Nishiwaki-Ohkawa T., Muto K., Kawamura R., Hirota T., Yagita K., Irle S., Kay S.A., Yoshimura T., Itami K.

Angewandte Chemie - International Edition2015年-

DOIScopus

詳細

ISSN:14337851

概要:The synthesis and functional analysis of KL001 derivatives, which are modulators of the mammalian circadian clock, are described. By using cutting-edge C-H activation chemistry, a focused library of KL001 derivatives was rapidly constructed, which enabled the identification of the critical sites on KL001 derivatives that induce a rhythm-changing activity along with the components that trigger opposite modes of action. The first period-shortening molecules that target the cryptochrome (CRY) were thus discovered. Detailed studies on the effects of these compounds on CRY stability implicate the existence of an as yet undiscovered regulatory mechanism. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Key mechanistic features of Ni-catalyzed C-H/C-O biaryl coupling of azoles and naphthalen-2-yl pivalates

Xu H., Muto K., Yamaguchi J., Zhao C., Itami K., Musaev D.G.

Journal of the American Chemical Society136(42)p.14834 - 148442014年-

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ISSN:27863

概要:The mechanism of the Ni-dcype-catalyzed C-H/C-O coupling of benzoxazole and naphthalen-2-yl pivalate was studied. Special attention was devoted to the base effect in the C-O oxidative addition and C-H activation steps as well as the C-H substrate effect in the C-H activation step. No base effect in the C(aryl)-O oxidative addition to Ni-dcype was found, but the nature of the base and C-H substrate plays a crucial role in the following C-H activation. In the absence of base, the azole C-H activation initiated by the C-O oxidative addition product Ni(dcype)(Naph)(PivO), 1B, proceeds via ΔG = 34.7 kcal/mol barrier. Addition of Cs2CO3 base to the reaction mixture forms the Ni(dcype)(Naph)[PivOCs·CsCO3], 3-Cs-clus, cluster complex rather than undergoing PivO- → CsCO3- ligand exchange. Coordination of azole to the resulting 3-Cs-clus complex forms intermediate with a weak Cs-heteroatom(azole) bond, the existence of which increases acidity of the activated C-H bond and reduces C-H activation barrier. This conclusion from computation is consistent with experiments showing that the addition of Cs2CO3 to the reaction mixture of 1B and benzoxazole increases yield of C-H/C-O coupling from 32% to 67% and makes the reaction faster by 3-fold. This emerging mechanistic knowledge was validated by further exploring base and C-H substrate effects via replacing Cs2CO3 with K2CO3 and benzoxazole (1a) with 1H-benzo[d]imidazole (1b) or quinazoline (1c). We proposed the modified catalytic cycle for the Ni(cod)(dcype)-catalyzed C-H/C-O coupling of benzoxazole and naphthalen-2-yl pivalate. (Chemical Equation Presented) © 2014 American Chemical Society.

β-selective C-H arylation of pyrroles leading to concise syntheses of lamellarins C and I

Ueda K., Amaike K., Maceiczyk R.M., Itami K., Yamaguchi J.

Journal of the American Chemical Society136(38)p.13226 - 132322014年-

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ISSN:27863

概要:The first general β-selective C-H arylation of pyrroles has been developed by using a rhodium catalyst. This C-H arylation reaction, which is retrosynthetically straightforward but results in unusual regioselectivity, could result in de novo syntheses of pyrrole-derived natural products and pharmaceuticals. As such, we have successfully synthesized polycyclic marine pyrrole alkaloids, lamellarins C and I, by using this β-selective arylation of pyrroles with aryl iodides (C-H/C-I coupling) and a new double C-H/C-H coupling as key steps. © 2014 American Chemical Society.

Branch-selective allylic C-H carboxylation of terminal alkenes by pd/sox catalyst

Kondo H., Yu F., Yamaguchi J., Liu G., Itami K.

Organic Letters16(16)p.4212 - 42152014年-

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ISSN:15237060

概要:A ligand-controlled branch-selective allylic C-H carboxylation through Pd catalysis is described. The developed catalytic system, which consists of Pd(OAc)2, sulfoxide-oxazoline (sox) as a ligand and benzoquinone as an oxidant, couples terminal alkenes and carboxylic acids to furnish the corresponding branched allylic esters with high regioselectivity. © 2014 American Chemical Society.

Nickel-catalyzed α-arylation of ketones with phenol derivatives

Takise R., Muto K., Yamaguchi J., Itami K.

Angewandte Chemie - International Edition53(26)p.6791 - 67942014年-

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ISSN:14337851

概要:The nickel-catalyzed α-arylation of ketones with readily available phenol derivatives (esters and carbamates) provides access to useful α-arylketones. For this transformation, 3,4-bis(dicyclohexylphosphino) thiophene (dcypt) was identified as a new, enabling, air-stable ligand for this transformation. The intermediate of an assumed C-O oxidative addition was isolated and characterized by X-ray crystal-structure analysis. The nickel-catalyzed α-arylation of ketones with readily available phenol derivatives (esters and carbamates) provides access to useful α-arylketones. The use of 3,4-bis(dicyclohexylphosphino)thiophene (dcypt) as an air-stable ligand enables this transformation. The intermediate of an assumed C-O oxidative addition was isolated and characterized by X-ray crystal-structure analysis. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Late-stage C-H coupling enables rapid identification of HDAC inhibitors: Synthesis and evaluation of NCH-31 analogues

Sekizawa H., Amaike K., Itoh Y., Suzuki T., Itami K., Yamaguchi J.

ACS Medicinal Chemistry Letters5(5)p.582 - 5862014年-

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ISSN:19485875

概要:We previously reported the discovery of NCH-31, a potent histone deacetylase (HDAC) inhibitor. By utilizing our C-H coupling reaction, we rapidly synthesized 16 analogues (IYS-1 through IYS-15 and IYS-Me) of NCH-31 with different aryl groups at the C4-position of 2-aminothiazole core of NCH-31. Subsequent biological testing of these derivatives revealed that 3-fluorophenyl (IYS-10) and 4-fluorophenyl (IYS-15) derivatives act as potent pan-HDAC inhibitor. Additionally, 4-methylphenyl (IYS-1) and 3-fluoro-4-methylphenyl (IYS-14) derivatives acted as HDAC6-insensitive inhibitors. The present work clearly shows the power of the late-stage C-H coupling approach to rapidly identify novel and highly active/selective biofunctional molecules. © 2014 American Chemical Society.

Manganese-catalyzed intermolecular C-H/C-H coupling of carbonyls and heteroarenes

Hattori K., Ziadi A., Itami K., Yamaguchi J.

Chemical Communications50(31)p.4105 - 41072014年-

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ISSN:13597345

概要:Manganese-catalyzed intermolecular C-H/C-H coupling of carbonyls and heteroarenes has been developed. The presence of NaIO4 as an oxidant is crucial for the catalytic reaction. These new, inexpensive reaction conditions allow the gram-scale synthesis of α-heteroaryl carboxylic acids. This journal is © the Partner Organisations 2014.

Diverse modifications of the 4-methylphenyl moiety of TAK-779 by late-stage Suzuki-Miyaura cross-coupling

Junker A., Schepmann D., Yamaguchi J., Itami K., Faust A., Kopka K., Wagner S., Wünsch B.

Organic and Biomolecular Chemistry12(1)p.177 - 1862014年-

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ISSN:14770520

概要:Chemokine receptor 5 (CCR5) antagonists provide a new therapeutic approach in the treatment of HIV-1 (AIDS). TAK-779 displays high affinity and selectivity for the CCR5 receptor and serves as a lead compound for the development of further antagonists. In order to increase the oral bioavailability replacement of the quaternary ammonium structure by a tertiary amine and modification of the 4-methylphenyl moiety were envisaged. Herein, a new synthetic strategy for the development of TAK-779 analogs by late stage diversification is reported. The Suzuki-Miyaura cross-coupling reactions allowed various modifications of the central amide building block 3 at the end of the synthesis leading to compounds 2f and 2h with a promising CCR5 binding affinity. © The Royal Society of Chemistry.

Programmed synthesis of arylthiazoles through sequential C-H couplings

Tani S., Uehara T.N., Yamaguchi J., Itami K.

Chemical Science5(1)p.123 - 1352014年-

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ISSN:20416520

概要:A programmed synthesis of privileged arylthiazoles via sequential C-H couplings catalyzed by palladium or nickel catalysts has been accomplished. This versatile protocol can supply all possible arylthiazole substitution patterns (2-aryl, 4-aryl, 5-aryl, 2,4-diaryl, 2,5-diaryl, 4,5-diaryl, and 2,4,5-triaryl) from an unfunctionalized thiazole platform by 11 distinct synthetic routes. We have generated over 150 arylthiazoles by using this methodology. We have applied this method to the rapid synthesis of fatostatin (SREBP inhibitor), and the gram-scale synthesis of triarylthiazoles has been demonstrated. © 2013 The Royal Society of Chemistry.

2,4- and 2,5-disubstituted arylthiazoles: Rapid synthesis by C-H coupling and biological evaluation

Lohrey L., Uehara T.N., Tani S., Yamaguchi J., Humpf H.-U., Itami K.

European Journal of Organic Chemistry2014(16)p.3387 - 33942014年-

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ISSN:1434193X

概要:Life-threatening infections caused by bacteria that have developed resistance to common antibiotics, such as methicillin-resistant Staphylococcus aureus (MRSA), have become a serious problem in hospitals and other areas all over the world. Thus, the development of an effective class of antibiotics against these bacteria is an urgent subject. Herein, we report a step-economical and diversity-oriented synthesis of a series of 2-arylidenehydrazinyl-4- arylthiazole and 2-arylidenehydrazinyl-5-arylthiazole analogues that utilizes C-H coupling methodologies. A library of 54 new congeners were synthesized and tested for their biological potential. Moreover, new knowledge regarding the structure-activity relationships (SARs) of these heterobiaryl compounds was collected. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Biaryl Synthesis through Metal-Catalyzed C-H Arylation

Yamaguchi J., Itami K.

Metal Catalyzed Cross-Coupling Reactions and More3p.1315 - 13872013年-

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ISSN:27863

Isolation, structure, and reactivity of an arylnickel(II) pivalate complex in catalytic C-H/C-O biaryl coupling

Muto K., Yamaguchi J., Lei A., Itami K.

Journal of the American Chemical Society135(44)p.16384 - 163872013年-

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ISSN:379980

概要:We describe mechanistic studies of a C-H/C-O biaryl coupling of 1,3-azoles and aryl pivalates catalyzed by Ni(cod)2/dcype. This study not only supports a catalytic cycle consisting of C-O oxidative addition, C-H nickelation, and reductive elimination but also provides insight into the dramatic ligand effect in C-H/C-O coupling. We have achieved the first synthesis, isolation and structure elucidation of an arylnickel(II) pivalate, which is an intermediate in the catalytic cycle after oxidative addition of a C-O bond. Furthermore, kinetic studies and kinetic isotope effect investigations reveal that the C-H nickelation is the turnover-limiting step in the catalytic cycle. © 2013 American Chemical Society.

Nickel-catalyzed direct coupling of heteroarenes

Yamaguchi J., Muto K., Amaike K., Yamamoto T., Itami K.

Yuki Gosei Kagaku Kyokaishi/Journal of Synthetic Organic Chemistry71(6)p.576 - 5872013年-

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ISSN:27863

概要:Nickel-catalyzed cross-coupling reactions have recently been receiving significant attention from the synthetic community as a way to construct carbon-carbon or carbon-heteroatom bonds, because nickel catalysts are less expensive and less toxic than palladium catalysts. We herein describe our recent developments in nickel-catalyzed biaryl coupling methodology, along with mechanistic studies and applications to the synthesis of natural products and pharmaceuticals. In particular, we focus on nickel-catalyzed direct coupling reactions in which "unreactive" bonds such as C-H, C-O, and C-C bonds are converted into biaryl moieties.

C-H alkenylation of azoles with enols and esters by nickel catalysis

Meng L., Kamada Y., Muto K., Yamaguchi J., Itami K.

Angewandte Chemie - International Edition52(38)p.10048 - 100512013年-

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ISSN:379980

概要:Rather u(Ni)que: Two new C-H alkenylation reactions, that is C-H/CO alkenylation and decarbonylative C-H alkenylation, of azoles are uniquely catalyzed by Ni/dcype. These azole alkenylation reactions are successfully applied to the convergent formal synthesis of siphonazoleB. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Aromatic C-H coupling with hindered arylboronic acids by Pd/Fe dual catalysts

Yamaguchi K., Kondo H., Yamaguchi J., Itami K.

Chemical Science4(9)p.3753 - 37572013年-

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詳細

ISSN:14337851

概要:An aerobic oxidative coupling of arenes/alkenes with arylboronic acids (C-H/C-B coupling) using catalytic Pd(ii)-sulfoxide-oxazoline (sox) ligand and iron-phthalocyanine (FePc) has been developed. This dual catalyst system enables the synthesis of sterically hindered heterobiaryls and styrene derivatives under air without stoichiometric co-oxidants. Additionally, this chemistry demonstrated an advance toward an enantioselective biaryl coupling through C-H functionalization. © 2013 The Royal Society of Chemistry.

Synthesis of thiophene-based TAK-779 analogues by C-H arylation

Junker A., Yamaguchi J., Itami K., Wünsch B.

Journal of Organic Chemistry78(11)p.5579 - 55862013年-

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ISSN:20416520

概要:A rapid synthesis of thiophene-based TAK-779 analogues 1 is reported using a late-stage diversification strategy. At the end of the synthesis, the key building block 2, which was prepared in six steps from thiophene, was arylated regioselectively at the α-position directly with iodoarenes. Since 2 offers several reactive positions, various established catalyst systems were tested. It was found that Crabtree catalyst (an Ir catalyst) converted efficiently and selectively the thiophene system 2 into 2-aryl-substituted compounds 9. The direct C-H arylation of 2 with electron-rich iodoarenes led to high yields, whereas electron-deficient iodoarenes required longer reaction times for complete conversion. A small set of diverse amides 1 was synthesized by hydrolysis of 9 and subsequent HATU coupling with primary amines 4. © 2013 American Chemical Society.

Improvement of σ1 receptor affinity by late-stage C-H-bond arylation of spirocyclic lactones

Meyer C., Neue B., Schepmann D., Yanagisawa S., Yamaguchi J., Würthwein E.-U., Itami K., Wünsch B.

Bioorganic and Medicinal Chemistry21(7)p.1844 - 18562013年-

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ISSN:223263

概要:The direct C-H-bond arylation of the complex spirocyclic lactones 13, 14, and 18 allows the introduction of diverse aryl moieties in the last step of the synthesis. A selective α-arylation of the thiophene moiety was performed with the catalytic system PdCl2/2,2′-bipyridyl/Ag 2CO3, whereas the β-position of the thiophene ring was addressed by using the alternative catalytic system PdCl2/ P[OCH(CF3)2]3/Ag2CO3. Due to electronic and steric reasons the arylation of the five-membered lactone 18 occurred in both α-positions providing 4′-mono-, 6′-mono- and 4′,6′-diarylated thiophenes 22-26a-c. Compounds with an additional aryl moiety at the 'upper left (top)' position (1′-position of 13, 3′-position of 14, 4′-position of 18) showed increased σ1 affinity compared to the non-arylated parent compounds. A phenyl moiety at the 'left' position (2′-position in 20a) also increased the σ1 affinity but to a lower extent. A considerable reduction of σ1 affinity was observed after introducing an aryl moiety in 6′-position of 18, which might result from shielding the tertiary amine, which is crucial for interaction with the σ1 receptor. The discussion of the experimental results is supported by high-level quantum chemical DFT-calculations of the NBO-charges of 13 and 18 and the relative energies of the related arylated products. © 2013 Elsevier Ltd. All rights reserved.

Palladium-Catalyzed C-H and C-N Arylation of Aminothiazoles with Arylboronic Acids

Uehara T.N., Yamaguchi J., Itami K.

Asian Journal of Organic Chemistry2(11)p.938 - 9422013年-

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ISSN:9680896

概要:[抄録情報がありません]

Recent progress in nickel-catalyzed biaryl coupling

Yamaguchi J., Muto K., Itami K.

European Journal of Organic Chemistry(1)p.19 - 302013年-

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ISSN:21935807

概要:Nickel catalysis for biaryl coupling reactions has received significant attention as a less expensive and less toxic alternative to "standard" palladium catalysis. Here we describe recent developments in nickel-catalyzed biaryl coupling methodology, along with mechanistic studies and applications. In particular we focus on nickel-catalyzed coupling reactions in which "unreactive" bonds such as C-H, C-O, and C-C bonds are converted into biaryl moieties. Biaryl coupling through nickel catalysis has been known for a few decades. The topic has recently resurfaced in synthetic chemistry, however, thanks to its use of ideal coupling partners such as simple arenes (Ar-H) and phenol derivatives (Ar-OR). In this microreview, recent achievements in nickel-catalyzed biaryl coupling are summarized. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Late-stage C-H bond arylation of spirocyclic σ 1 ligands for analysis of complementary σ 1 receptor surface

Meyer C., Schepmann D., Yanagisawa S., Yamaguchi J., Itami K., Wünsch B.

European Journal of Organic Chemistry(30)p.5972 - 59792012年-

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ISSN:1434193X

概要:Direct C-H bond arylation in the α- and β-positions of spirocyclic thiophenes containing various functional groups (amine, ether, acetal, lactone) was accomplished. Selective phenylation in the α-position of the thiophene ring was achieved by using the catalytic system PdCl 2/bipy/Ag 2CO 3. The introduction of phenyl moieties to the β-position was performed with the catalytic system PdCl 2/P[OCH(CF 3) 2] 3/Ag 2CO 3. Even the five-membered lactone 10 with an electron-withdrawing carbonyl moiety directly attached to the thiophene ring was arylated. Spirocyclic thiophenes substituted with a phenyl moiety in position A (top position) or B (left position) display low nanomolar Ï 1 affinities (e.g., 4a: K i = 1.6 nM; 5a: K i = 2.4 nM), indicating an additional hydrophobic pocket on the complementary Ï 1 receptor protein. A phenyl moiety in position C (at the bottom position) is not tolerated by the Ï 1 receptor (e.g., 12: K i = 483 nM). However, an additional phenyl moiety in position A is able to compensate at least partially the unfavorable effects of the phenyl moiety in position C. Diverse spirocyclic thiophenes were synthesized regioselectively by direct C-H bond arylation using the catalytic systems PdCl 2/bipy/Ag 2CO 3 and PdCl 2/ P[OCH(CF 3) 2] 3/Ag 2CO 3. Compounds bearing the phenyl moiety at the top position and the sulfur atom in left position show the highest Ï 1 affinity. © 2012 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Pd-catalyzed direct C-H bond functionalization of spirocyclic σ1 ligands: Generation of a pharmacophore model and analysis of the reverse binding mode by Docking into a 3D homology model of the σ1 receptor

Meyer C., Schepmann D., Yanagisawa S., Yamaguchi J., Dal Col V., Laurini E., Itami K., Pricl S., Wünsch B.

Journal of Medicinal Chemistry55(18)p.8047 - 80652012年-

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ISSN:1434193X

概要:To explore the hydrophobic binding region of the σ1 receptor protein, regioisomeric spirocyclic thiophenes 9-11 were developed as versatile building blocks. Regioselective α- and β-arylation using the catalyst systems PdCl2/bipy/Ag2CO3 and PdCl2/P[OCH(CF3)2]3/Ag 2CO3 allowed the introduction of various aryl moieties at different positions in the last step of the synthesis. The increasing σ1 affinity in the order 4 < 5/6 < 7/8 indicates that the positions of the additional aryl moiety and the S atom in the spirocyclic thiophene systems control the σ1 affinity. The main features of the pharmacophore model developed for this class of σ1 ligands are a positive ionizable group, a H-bond acceptor group, two hydrophobic moieties, and one hydrophobic aromatic group. Docking of the ligands into a σ1 3D homology model via molecular mechanics/Poisson-Boltzmann surface area calculations led to a very good correlation between the experimentally determined and estimated free energy of receptor binding. These calculations support the hypothesis of a reverse binding mode of ligands bearing the aryl moiety at the "top" (compounds 2, 3, 7, and 8) and "left" (compounds 4, 5, and 6) positions, respectively. © 2012 American Chemical Society.

Pd- and Cu-catalyzed C-H arylation of indazoles

Hattori K., Yamaguchi K., Yamaguchi J., Itami K.

Tetrahedron68(37)p.7605 - 76122012年-

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ISSN:222623

概要:The palladium- and copper-catalyzed C-H arylation reactions of 1H- and 2H-indazoles with haloarenes are described. A PdCl 2/phen/Ag 2CO 3/K 3PO 4 catalytic system is effective for the C-H arylation of 1H- and 2H-indazoles with haloarenes, whereas a less expensive CuI/phen/LiOt-Bu catalytic system is applicable to the C-H coupling of substituted 2H-indazoles and iodoarenes. The utility of newly developed catalyst was demonstrated in the rapid synthesis of YC-1 (an antitumor agent) and YD-3 (platelet anti-aggregating agent). These new reactions represent important direct functionalization tools of indazoles, well-known bioisosteres of pharmaceutically important indole core. © 2012 Elsevier Ltd. All rights reserved.

C-H bond functionalization: Emerging synthetic tools for natural products and pharmaceuticals

Yamaguchi J., Yamaguchi A.D., Itami K.

Angewandte Chemie - International Edition51(36)p.8960 - 90092012年-

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ISSN:404020

概要:The direct functionalization of C-H bonds in organic compounds has recently emerged as a powerful and ideal method for the formation of carbon-carbon and carbon-heteroatom bonds. This Review provides an overview of C-H bond functionalization strategies for the rapid synthesis of biologically active compounds such as natural products and pharmaceutical targets. The ideal case: The direct functionalization of C-H bonds in organic compounds has recently emerged as a powerful and ideal method for the formation of carbon-carbon and carbon-heteroatom bonds. This Review provides an overview of C-H functionalization strategies for the rapid synthesis of biologically active compounds such as natural products and pharmaceutical targets. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Decarbonylative C-H coupling of azoles and aryl esters: Unprecedented nickel catalysis and application to the synthesis of muscoride A

Amaike K., Muto K., Yamaguchi J., Itami K.

Journal of the American Chemical Society134(33)p.13573 - 135762012年-

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ISSN:27863

概要:A nickel-catalyzed decarbonylative C-H biaryl coupling of azoles and aryl esters is described. The newly developed catalytic system does not require the use of expensive metal catalysts or silver- or copper-based stoichiometric oxidants. We have successfully applied this new C-H arylation reaction to a convergent formal synthesis of muscoride A. © 2012 American Chemical Society.

Hindered biaryls by C-H coupling: Bisoxazoline-Pd catalysis leading to enantioselective C-H coupling

Yamaguchi K., Yamaguchi J., Studer A., Itami K.

Chemical Science3(6)p.2165 - 21692012年-

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ISSN:20416520

概要:A new Pd-catalyzed C-H/C-B coupling of sterically hindered heteroarenes and arylboronic acids has been identified. The newly established Pd(OAc) 2/bisoxazoline/TEMPO system not only enables the synthesis of sterically hindered heterobiaryls but also offers an opportunity for enantioselective biaryl coupling through C-H functionalization. © 2012 The Royal Society of Chemistry.

Mechanistic studies on the Pd-catalyzed direct C-H arylation of 2-substituted thiophene derivatives with arylpalladium bipyridyl complexes

Steinmetz M., Ueda K., Grimme S., Yamaguchi J., Kirchberg S., Itami K., Studer A.

Chemistry - An Asian Journal7(6)p.1256 - 12602012年-

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ISSN:18614728

概要:Direct C-H phenylation of 2-ethylthiophene and 2-chlorothiophene with PhPdI(bipy) complex to form either the corresponding 4-phenyl or 5-phenylthiophene derivative is studied under stoichiometric conditions using various Lewis acids as additives. It is shown that reactions occur via the corresponding cationic Pd complex (PhPdbipy +) and that the counteranion determines the regioselectivity. High-level DFT calculations reveal that C-C bond formation occurs via a carbopalladation pathway and not via electrophilic palladation. These calculations give some indications regarding the regioselectivity of the thiophene arylation. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Nickel-catalyzed C-H/C-O coupling of azoles with phenol derivatives

Muto K., Yamaguchi J., Itami K.

Journal of the American Chemical Society134(1)p.169 - 1722012年-

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ISSN:27863

概要:The first nickel-catalyzed C-H bond arylation of azoles with phenol derivatives is described. The new Ni(cod) 2/dcype catalytic system is active for the coupling of various phenol derivatives such as esters, carbamates, carbonates, sulfamates, triflates, tosylates, and mesylates. With this C-H/C-O biaryl coupling, we synthesized a series of privileged 2-arylazoles, including biologically active alkaloids. Moreover, we demonstrated the utility of the present reaction for functionalizing estrone and quinine. © 2011 American Chemical Society.

Synthesis of dragmacidin D via direct C-H couplings

Mandal D., Yamaguchi A.D., Yamaguchi J., Itami K.

Journal of the American Chemical Society133(49)p.19660 - 196632011年-

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ISSN:27863

概要:Dragmacidin D, an emerging biologically active marine natural product, has attracted attention as a lead compound for treating Parkinson's and Alzheimer's diseases. Prominent structural features of this compound are the two indole-pyrazinone bonds and the presence of a polar aminoimidazole unit. We have established a concise total synthesis of dragmacidin D using direct C-H coupling reactions. Methodological developments include (i) Pd-catalyzed thiophene-indole C-H/C-I coupling, (ii) Pd-catalyzed indole-pyrazine N-oxide C-H/C-H coupling, and (iii) acid-catalyzed indole-pyrazinone C-H/C-H coupling. These regioselective catalytic C-H couplings enabled us to rapidly assemble simple building blocks to construct the core structure of dragmacidin D in a step-economical fashion. © 2011 American Chemical Society.

Exploitation of an additional hydrophobic pocket of σ 1 receptors: Late-stage diverse modifications of spirocyclic thiophenes by C-H bond functionalization

Meyer C., Neue B., Schepmann D., Yanagisawa S., Yamaguchi J., Würthwein E.-U., Itami K., Wünsch B.

Organic and Biomolecular Chemistry9(23)p.8016 - 80292011年-

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ISSN:14770520

概要:The hypothesis that the σ 1 receptor will tolerate an additional aryl moiety in position 1 of the spirocyclic system was based on spirocyclic pyrazole derivatives, pharmacophore models of σ 1 receptor ligands and DFT calculations. The strategy of introducing the aryl residue at the final step of the synthesis allowed the preparation of a large set of diverse ligands for the exploitation of the hydrophobic pocket of the σ 1 receptor protein. The catalyst system PdCl 2/2,2′-bipyridyl/Ag 2CO 3 is able to introduce various aryl groups onto the α-positions of spirocyclic thiophene derivatives 5 and 6 to afford the target aryl-appended spirocyclic thiophenes 3 and 4. Although the σ 1 affinity of the 1-phenyl substituted spirocyclic thiophenes 3a and 4a is slightly reduced compared with the σ 1 affinity of the non-arylated compounds 5 and 6, both compounds represent very potent σ 1 receptor ligands (3a: K i = 4.5 nM; 4a: K i = 1.0 nM). This result indicates that an aryl moiety in position 1 is well tolerated by the σ 1 receptor protein. The substitution pattern of the additional phenyl moiety has only weak effects on the σ 1 affinity. Even ligands 3f and 4h with extended naphthyl residue show high σ 1 affinity. However, decrease of σ 1 affinity by extension of the π-system to a biphenylyl substituent (4j: K i = 30 nM) indicates that the biphenylyl residue is too large for the primary hydrophobic binding pocket of the σ 1 receptor. © The Royal Society of Chemistry 2011.

Enantioselective total syntheses of (-)-palau'Amine, (-)-axinellamines, and (-)-massadines

Seiple I.B., Su S., Young I.S., Nakamura A., Yamaguchi J., Jørgensen L., Rodriguez R.A., Ömalley D.P., Gaich T., Köck M., Baran P.S.

Journal of the American Chemical Society133(37)p.14710 - 147262011年-

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ISSN:27863

概要:Dimeric pyrrole-imidazole alkaloids represent a rich and topologically unique class of marine natural products. This full account will follow the progression of efforts that culminated in the enantioselective total syntheses of the most structurally ornate members of this family: the axinellamines, the massadines, and palau'Amine. A bio-inspired approach capitalizing on the pseudo-symmetry of the members of this class is recounted, delivering a deschloro derivative of the natural product core. Next, the enantioselective synthesis of the chlorocyclopentane core featuring a scalable, catalytic, enantioselective Diels-Alder reaction of a 1-siloxydiene is outlined in detail. Finally, the successful divergent conversion of this core to each of the aforementioned natural products, and the ensuing methodological developments, are described. © 2011 American Chemical Society.

Nickel-catalyzed C-H arylation of azoles with haloarenes: Scope, mechanism, and applications to the synthesis of bioactive molecules

Yamamoto T., Muto K., Komiyama M., Canivet J., Yamaguchi J., Itami K.

Chemistry - A European Journal17(36)p.10113 - 101222011年-

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詳細

ISSN:9476539

概要:Novel nickel-based catalytic systems for the C-H arylation of azoles with haloarenes and aryl triflates have been developed. We have established that Ni(OAc) 2/bipy/LiOtBu serves as a general catalytic system for the coupling with aryl bromides and iodides as aryl electrophiles. For couplings with more challenging electrophiles, such as aryl chlorides and triflates, the Ni(OAc) 2/dppf (dppf=1,1′-bis(diphenylphosphino)ferrocene) system was found to be effective. Thiazoles, benzothiazoles, oxazoles, benzoxazoles, and benzimidazoles can be used as the heteroarene coupling partner. Upon further investigation, we discovered a new protocol for the present coupling using Mg(OtBu) 2 as a milder and less expensive alternative to LiOtBu. Attempts to reveal the mechanism of this nickel-catalyzed heterobiaryl coupling are also described. This newly developed methodology has been successfully applied to the syntheses of febuxostat (a xanthine oxidase inhibitor that is effective for the treatment of gout and hyperuricemia), tafamidis (effective for the treatment of TTR amyloid polyneuropathy), and texaline (a natural product having antitubercular activity). Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Oxidative C-H/C-H coupling of azine and indole/pyrrole nuclei: Palladium catalysis and synthesis of eudistomin U

Yamaguchi A.D., Mandal D., Yamaguchi J., Itami K.

Chemistry Letters40(6)p.555 - 5572011年-

DOIScopus

詳細

ISSN:3667022

概要:We have developed a palladium-catalyzed C-H/C-H coupling reaction of indoles or pyrroles with azine N-oxides. The reaction proceeds selectively at the C3 position of indoles/pyrroles and the C2 position of azine N-oxides. Furthermore, we have accomplished the synthesis of marine indole alkaloid eudistomin U by utilizing this newly developed C-H/C-H coupling reaction. © 2011 The Chemical Society of Japan.

Oxidative biaryl coupling of thiophenes and thiazoles with arylboronic acids through palladium catalysis: Otherwise difficult C4-selective C-H arylation enabled by boronic acids

Kirchberg S., Tani S., Ueda K., Yamaguchi J., Studer A., Itami K.

Angewandte Chemie - International Edition50(10)p.2387 - 23912011年-

DOIScopus

詳細

ISSN:14337851

概要:(Chemical Equation Presented) It adds up to 4! Thiophenes and thiazoles can be arylated in the 4- rather than the expected 5-position in a new C-H functionalization reaction (see scheme; TEMPO: 2,2,6,6-tetramethylpiperidine-N- oxyl). The boronic acid proved to be the key to achieving the otherwise difficult C4 selectivity. The method was applied to a concise synthesis of a key pharmacological structure with potential for treatment of Alzheimers disease. © 2011 Wiley-VCH Verlag GmbH & Co. KGaA.

A general catalyst for the β-selective C - H bond arylation of thiophenes with iodoarenes

Ueda K., Yanagisawa S., Yamaguchi J., Itami K.

Angewandte Chemie - International Edition49(47)p.8946 - 89492010年-

DOIScopus

詳細

ISSN:14337851

概要:Open access: The normally less-reactive β position of thiophenes was previously inaccessible to direct functionalization. However, the β selectivity observed with the catalytic system PdCl 2/P{OCH(CF 3) 2} 3/Ag 2CO 3 in the arylation of thiophenes with iodoarenes (see scheme) is a remarkably general phenomenon applicable to unsubstituted, monosubstituted, and disubstituted thiophene derivatives, as well as thiophene-containing fused aromatic compounds. © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Syntheses of fumagillin and ovalicin

Yamaguchi J., Hayashi Y.

Chemistry - A European Journal16(13)p.3884 - 39012010年-

DOIScopus

詳細

ISSN:9476539

概要:(Figure Presented) This review focuses on the synthetic strategies used for the construction of fumagillin, ovalicin, and other natural products of this family that are known angiogenesis inhibitors. These compounds are comprised of a cyclohexane framework, two epoxides, and five or six contiguous stereogenic centers. The first total syntheses of fumagillin and ovalicin were reported by Corey in 1972 and 1985, respectively. There were numerous studies directed at these natural products in the decades that followed with many reports appearing in the year 2000 or later. Despite the relatively small size of these molecules, their syntheses highlight the efficient construction of stereogenic centers in organic synthesis. © 2010 Wiley-VCH Verlag GmbH& Co. KGaA.

Total synthesis of palau'amine

Seiple I.B., Su S., Young I.S., Lewis C.A., Yamaguchi J., Baran P.S.

Angewandte Chemie - International Edition49(6)p.1095 - 10982010年-

DOIScopus

詳細

ISSN:14337851

概要:(Figure Presented) Worth the wait: The long anticipated total synthesis of palau'amine has been accomplished by a route featuring highly chemoselective transformations, cascade reactions, and a remarkable transannular cyclization to secure the unprecedented trans-5,5 ring junction (shown in red). © 2010 Wiley-VCH Verlag GmbH & Co. KGaA.

Fe-catalyzed oxidative coupling of heteroarenes and methylamines

Ohta M., Quick M.P., Yamaguchi J., Wünsch B., Itami K.

Chemistry - An Asian Journal4(9)p.1416 - 14192009年-

DOIScopus

詳細

ISSN:18614728

概要:[抄録情報がありません]

Nickel-catalyzed biaryl coupling of heteroarenes and aryl halides/triflates

Canivet J., Yamaguchi J., Ban I., Itami K.

Organic Letters11(8)p.1733 - 17362009年-

DOIScopus

詳細

ISSN:15237060

概要:Ni-based catalytic systems for the arylation of heteroarenes with aryl halides and triflates have been established. Ni(OAc) 2/bipy is a general catalyst for aryl bromides/iodides, and Ni(OAc) 2/dppf is effective for aryl chlorides/triflates. Thiazole, benzothiazole, oxazole, benzoxazole, and benzimidazole are applicable as heteroarene coupling partners. A rapid synthesis of febuxostat, a drug for gout and hyperuricemia, is also demonstrated.© 2009 American Chemical Society.

Asymmetrie total synthesis of a natural product using catalytic enantioselective stereoablative reactions

Yamaguchi J.

Yuki Gosei Kagaku Kyokaishi/Journal of Synthetic Organic Chemistry67(2)p.166 - 1682009年-

Scopus

詳細

ISSN:379980

概要:Catalytic enantioselective Stereoablative reactions represent a unique approach to the preparation of enantioenriched materials, wherein a catalytic method destroys, at least temporarily, stereogenic elements of a molecule. This review introduces a recent example of novel approaches in asymmetric catalytic methods for stereoablation, as well as the use of a new Stereoablative reaction in a concise synthesis of the marine diterpenoid (-)-cyanthiwigin F.

The asymmetric total synthesis of (+)-cytotrienin A, an ansamycin-type anticancer drug

Hayashi Y., Shoji M., Ishikawa H., Yamaguchi J., Tamura T., Imai H., Nishigaya Y., Takabe K., Kakeya H., Osada H.

Angewandte Chemie - International Edition47(35)p.6657 - 66602008年-

DOIScopus

詳細

ISSN:14337851

概要:(Chemical Equation Presented) A star-studded lineup: (+)-Cytotrienin A was the target of an asymmetric total synthesis featuring an enantioselective aldol reaction, α-aminoxylation, deoxygenation, and a ring-closing metathesis to form the 21-membered macrolactam. This first total synthesis confirms the relative and absolute confguration of the molecule. © 2008 Wiley-VCH Verlag GmbH & Co. KGaA.

Total synthesis of (±)-axinellamines A and B

O'Malley D.P., Yamaguchi J., Young I.S., Seiple I.B., Baran P.S.

Angewandte Chemie - International Edition47(19)p.3581 - 35832008年-

DOIScopus

詳細

ISSN:14337851

概要:(Chemical Equation Presented) Chemoselective by design: The first total synthesis of members of the axinellamine/ palau'amine/massadine class of pyrrole-imidazole alkaloids features unconventional transformations on completely unprotected polyamino and hydroxylated substrates and a new method for chemoselective oxidations in such settings. © 2008 Wiley-VCH Verlag GmbH & Co. KGaA.

Synthesis of 1,9-dideoxy-pre-axinellamine

Yamaguchi J., Seiple I.B., Young I.S., O'Malley D.P., Maue M., Baran P.S.

Angewandte Chemie - International Edition47(19)p.3578 - 35802008年-

DOIScopus

詳細

ISSN:14337851

概要:(Chemical Equation Presented) Within reach: A 19-step route to 1,9-dideoxy-pre-axinellamine has been designed and executed. This key compound represents a hypothetical precursor to an entire family of alkaloid natural products. © 2008 Wiley-VCH Verlag GmbH & Co. KGaA.

Direct asymmetric α-amination of cyclic ketones catalyzed by siloxyproline

Hayashi Y., Aratake S., Imai Y., Hibino K., Chen Q.-Y., Yamaguchi J., Uchimaru T.

Chemistry - An Asian Journal3(2)p.225 - 2322008年-

DOIScopus

詳細

ISSN:18614728

概要:trans-tert-Butyldimethylsiloxy-l-proline displays greater catalytic activity and affords higher enantioselectivity than the parent proline in the a-amination reaction of carbonyl compounds with azodicarboxylate. A quantum mechanical calculation reveals the structure of the transition state. In the presence of a catalytic amount of siloxyproline and water (3-9 equiv), α-amino carbonyl derivatives, which are important synthetic intermediates, are obtained in good yield and with excellent enantioselectivity. © 2008 Wiley-VCH Verlag GmbH&Co. KGaA.

Organocatalyst-mediated enantioselective intramolecular aldol reaction featuring the rare combination of aldehyde as nucleophile and ketone as electrophile

Hayashi Y., Sekizawa H., Yamaguchi J., Gotoh H.

Journal of Organic Chemistry72(17)p.6493 - 64992007年-

DOIScopus

詳細

ISSN:223263

概要:(Chemical Equation Presented) The trifluoroacetic acid salt of 2-(pyrrolidinylmethyl)pyrrolidine was found to be an effective organocatalyst of an asymmetric intramolecular aldol reaction, affording bicyclo[4.3.0]nonane derivatives with a high enantioselectivity, in which the rare combination of aldehyde as a nucleophile and ketone as an electrophile was realized. © 2007 American Chemical Society.

Total synthesis of marinomycins A-C and of their monomeric counterparts monomarinomycin A and iso-monomarinomycin A

Nicolaou K.C., Nold A.L., Milburn R.R., Schindler C.S., Cole K.P., Yamaguchi J.

Journal of the American Chemical Society129(6)p.1760 - 17682007年-

DOIScopus

詳細

ISSN:27863

概要:Marinomycins A-C (1-3), and their monomeric analogues monomarinomycin A (m-1) and iso-monomarinomycin A (m-2), were synthesized by a convergent strategy from key building blocks ketophosphonate 5, aldehyde 6, and dienyl bromide carboxylic acid 7. The first attempt to construct marinomycin A [1, convertible to marinomycins B (2) and C (3) by light] by direct Suzuki-type dimerization/ cyclization of boronic acid dienyl bromide 4 led to premature ring closure to afford, after global desilylation, monomarinomycin A (m-1) and iso-monomarinomycin A (m-2) in good yield and only small amounts (≤2%) of the desired product. A subsequent stepwise approach based on Suzuki-type couplings improved considerably the overall yield of marinomycin A (1), and hence of marinomycins B (2) and C (3). Alternative direct dimerization approaches based on the Stille and Heck coupling reactions also led to monomarinomycins A (m-1 and m-2), but failed to deliver useful amounts of marinomycin A (1). © 2007 American Chemical Society.

Enantio- and diastereoselective total synthesis of (+)-panepophenanthrin, a ubiquitin-activating enzyme inhibitor, and biological properties of its new derivatives

Matsuzawa M., Kakeya H., Yamaguchi J., Shoji M., Onose R., Osada H., Hayashi Y.

Chemistry - An Asian Journal1(6)p.845 - 8512006年-

DOIScopus

詳細

ISSN:18614728

概要:The asymmetric total synthesis of (+)-panepophenanthrin, an inhibitor of ubiquitin-activating enzyme (E1), has been accomplished using catalytic asymmetric α aminoxylation of 1,4-cyclohexanedione monoethylene ketal as a key step, followed by several diastereoselective reactions. The biomimetic Diels-Alder reaction of a monomer precursor was found to proceed efficiently in water. The investigation of the biological properties of new derivatives of (+)-panepophenanthrin enabled us to develop new cell-permeable E1 inhibitors, RKTS-80, -81, and -82. © 2006 Wiley-VCH Verlag GmbH & Co. KGaA.

Large nonlinear effect observed in the enantiomeric excess of proline in solution and that in the solid state

Hayashi Y., Matsuzawa M., Yamaguchi J., Yonehara S., Matsumoto Y., Shoji M., Hashizume D., Koshino H.

Angewandte Chemie - International Edition45(28)p.4593 - 45972006年-

DOIScopus

詳細

ISSN:14337851

概要:(Chemical Equation Presented) A clue to the origin of chirality? A solution of proline with high enantiomeric excess (85-99% ee) was obtained from solid proline of only 10% ee through novel dissolution and crystallization processes (see scheme). This observation may be an explanation for the origin of chirality on Earth. © 2006 Wiley-VCH Verlag GmbH & Co. KGaA.

Concise enantio- and diastereoselective total syntheses of fumagillol, RK-805, FR65814, ovalicin, and 5-demethylovalicin

Yamaguchi J., Toyoshima M., Shoji M., Kakeya H., Osada H., Hayashi Y.

Angewandte Chemie - International Edition45(5)p.789 - 7932006年-

DOIScopus

詳細

ISSN:14337851

概要:(Chemical Equation Presented) L-Proline-mediated α-aminoxylation is a key step in the enantio- and diastereoselective total syntheses of fumagillin, ovalicin, and related compounds (see scheme). These compounds contain a cyclohexane ring, two epoxides, and five or six contiguous stereogenic centers, and they display anti-angiogenesis or immunosuppressive properties. © 2006 Wiley-VCH Verlag GmbH & Co. KGaA.

Determination by asymmetric total synthesis of the absolute configuration of lucilactaene, a cell-cycle inhibitor in p53-transfected cancer cells

Yamaguchi J., Kakeya H., Uno T., Shoji M., Osada H., Hayashi Y.

Angewandte Chemie - International Edition44(20)p.3110 - 31152005年-

DOIScopus

詳細

ISSN:14337851

概要:(Chemical Equation Presented) A biomimetic pathway to lucilactaene (1) from NG-391 has been developed which involves stereoselective reactions under very mild conditions. It was demonstrated that 1 racemizes rapidly, and the conditions under which racemization occurs were elucidated. Lucilactaene (1) isolated under neutral conditions is racemic, which suggests that either the natural product is racemized rapidly in the mycelia, or racemic 1 is biosynthesized. © 2005 Wiley-VCH Verlag GmbH & Co. KGaA.

A highly active 4-siloxyproline catalyst for asymmetric synthesis

Hayashi Y., Yamaguchi J., Hibino K., Sumiya T., Urushima T., Shoji M., Hashizume D., Koshino H.

Advanced Synthesis and Catalysis346(12)p.1435 - 14392004年-

DOIScopus

詳細

ISSN:16154150

概要:trans-4-tert-Butyldimethylsiloxy-L-proline displays a greater catalytic activity than the parent proline without compromising the enantioselectivity, which widens the substrate scope in the α-aminoxylation of carbonyl compounds, as well as O-nitrosoaldol/Michael, and Mannich reactions.

Structure-activity relationships of epolactaene derivatives: Structural requirements for inhibition of Hsp60 chaperone activity

Nagumo Y., Kakeya H., Yamaguchi J., Uno T., Shoji M., Hayashi Y., Osada H.

Bioorganic and Medicinal Chemistry Letters14(17)p.4425 - 44292004年-

DOIScopus

詳細

ISSN:0960894X

概要:Epolactaene derivatives were synthesized and their ability to inhibit the growth of human cancer cell lines was tested. These derivatives were further analyzed for their ability to affect human heat shock protein 60 (Hsp60). We discovered the structural characteristics important for the ability to bind to Hsp60 and the fundamental role of α,β-unsaturated ketone in inhibiting Hsp60 chaperone activity. Epolactaene is a microbial metabolite isolated from the fungal strain Penicillium sp. It arrests the cell cycle at the G 0/G 1 phase and induces the outgrowth of neurites in human neuroblastoma SH-SY5Y cells. In this communication, we report the structure-activity relationships (SARs) of new epolactaene derivatives, including those lacking the epoxylactam moiety and having various side chains. These derivatives were evaluated for their ability to inhibit the growth of human cancer cell lines. They were also analyzed for their ability to affect human heat shock protein 60 (Hsp60), which we have already identified as a protein that binds to epolactaene. We also identified the important structural framework of epolactaene/ETB (epolactaene tertiary butyl ester) for not only binding to Hsp60 but also inhibiting Hsp60 chaperone activity. © 2004 Elsevier Ltd. All rights reserved.

Direct proline-catalyzed asymmetric α-aminoxylation of aldehydes and ketones

Hayashi Y., Yamaguchi J., Sumiya T., Hibino K., Shoji M.

Journal of Organic Chemistry69(18)p.5966 - 59732004年-

DOIScopus

詳細

ISSN:223263

概要:The direct proline-catalyzed asymmetric α-aminoxylation of aldehydes and ketones has been developed using nitrosobenzene as an oxygen source, affording α-anilinoxy-aldehydes and -ketones with excellent enantioselectivity. Reaction conditions have been optimized, and low temperature (-20 °C) was found to be a key for the successful α-aminoxylation of aldehydes, while slow addition of nitrosobenzene is essential for that of ketones. The scope of the reaction is presented.

Direct proline-catalyzed asymmetric α-aminoxylation of ketones

Hayashi Y., Yamaguchi J., Sumiya T., Shoji M.

Angewandte Chemie - International Edition43(9)p.1112 - 11152004年-

DOIScopus

詳細

ISSN:14337851

概要:Nitrosobenzene is the oxygen source in the direct catalytic enantioselective α-aminoxylation of ketones catalyzed by L-proline [Eq. (1)]. Versatile α-aminoxylated ketones are obtained in high yield and with excellent enantioselectivities.

Direct proline catalyzed asymmetric α-aminooxylation of aldehydes

Hayashi Y., Yamaguchi J., Hibino K., Shoji M.

Tetrahedron Letters44(45)p.8293 - 82962003年-

DOIScopus

詳細

ISSN:404039

概要:The direct catalytic enantioselective α-aminooxylation of aldehydes has been developed using nitrosobenzene as the oxygen source and L-proline as catalyst, affording versatile α-aminooxylated aldehydes in high yield with excellent enantioselectivities. © 2003 Elsevier Ltd. All rights reserved.

Asymmetric total synthesis of pseurotin A

Hayashi Y., Shoji M., Yamaguchi S., Mukaiyama T., Yamaguchi J., Kakeya H., Osada H.

Organic Letters5(13)p.2287 - 22902003年-

DOIScopus

詳細

ISSN:15237060

概要:(Matrix presented) The asymmetric total syntheses of pseurotin A and 8-O-demethylpseurotin A have been accomplished. Key reactions are a NaH-promoted intramolecular cyclization of an alkynylamide to form a γ-lactam, an aldol reaction of a benzylidene-substituted ketone, and the late-stage introduction of the benzoyl group by a selective oxidation of a benzylidene moiety with dimethyldioxirane (DMD).

Diastereoselective total synthesis of both enantiomers of epolactaene

Hayashi Y., Kanayama J., Yamaguchi J., Shoji M.

Journal of Organic Chemistry67(26)p.9443 - 94482002年-

DOIScopus

詳細

ISSN:223263

概要:A stereocontrolled total synthesis of both the (+)- and (-)-epolactaene ((+)- and (-)-1) enantiomers from tetrahydropyran-2-ol is described. The following reactions in this synthesis are particularly noteworthy: (1) the stereoselective construction of the conjugated (E,E,E)-triene by a combination of kinetic deprotonation and thermodynamic equilibration, (2) the E-selective Knoevenagel condensation of β-ketonitrile 33 with a chiral 2-alkoxyaldehyde, (3) a diastereoselective epoxidation achieved using a bulky nucleophile (TrOOLi) and an appropriate protecting group, (4) the mild hydrolysis of an α-epoxy nitrile by silica gel on TLC facilitated by hydroxyl-mediated, intramolecular assistance.

The diastereoselective asymmetric total synthesis of NG-391, a neuronal cell-protecting molecule

Hayashi Y., Yamaguchi J., Shoji M.

Tetrahedron58(49)p.9839 - 98462002年-

DOIScopus

詳細

ISSN:404020

概要:The stereocontrolled total synthesis of (+)-NG-391, a neuronal cell-protecting molecule, is described along with the determination of its absolute stereochemistry. The following reactions in this synthesis are particularly noteworthy: (1) The stereoselective construction of the conjugated (E,E,E,E,E)-pentaene from an (E,E,E)-alcohol using an IBX oxidation followed by stereoselective Horner-Emmons reaction. (2) The (E)-selective Knoevenagel condensation of a β-ketonitrile with a chiral 2-alkoxyaldehyde prepared from (S)-malic acid. (3) A diastereoselective epoxidation. © 2002 Elsevier Science Ltd. All rights reserved.

Asymmetric total synthesis of (-)-azaspirene, a novel angiogenesis inhibitor

Hayashi Y., Shoji M., Yamaguchi J., Sato K., Yamaguchi S., Mukaiyama T., Sakai K., Asami Y., Kakeya H., Osada H.

Journal of the American Chemical Society124(41)p.12078 - 120792002年-

DOIScopus

詳細

ISSN:27863

概要:The asymmetric total synthesis of (-)-azaspirene, an angiogenesis inhibitor, has been accomplished, establishing its absolute stereochemistry. The key steps are a MgBr2·OEt2-mediated, diastereoselective Mukaiyama aldol reaction, a NaH-promoted, intramolecular cyclization of an alkynylamide, and the aldol reaction of a ketone containing functionalized γ-lactam moiety without protection of tert-alcohol and amide functionalities. Copyright © 2002 American Chemical Society.

Total synthesis of (+)-epoxyquinols A and B

Shoji M., Yamaguchi J., Kakeya H., Osada H., Hayashi Y.

Angewandte Chemie - International Edition41(17)p.3192 - 31942002年-

DOIScopus

詳細

ISSN:14337851

概要:A highly stereoselective HfCl4-mediated Diels-Alder reaction of furan and the chiral acrylate ester of Corey's auxiliary to subsequently give 1, and the realization of the postulated biosynthetic pathway for the construction of epoxyquinols A and B, namely, oxidative 6π electrocyclization, followed by Diels-Alder reaction of the unprotected monomer are the key steps in the asymmetric total synthesis of (+)-epoxyquinols A and B.

講演・口頭発表等

芳香族分子の新奇カップリング法・合成法の開発

山口潤一郎

日本薬学会東海支部特別講演会2017年07月13日

詳細

開催地:岐阜薬科大学

Aromatic Molecules: Decarbonylative Coupling and Multiple Arylation

山口潤一郎

Boston University2017年06月27日

詳細

開催地:Boston University

Aromatic Molecules: Decarbonylative Coupling and Multiple Arylation

山口潤一郎

Boston College2017年06月26日

詳細

開催地:Boston College

Decarbonylative transformation of aromatic esters and multi-arylation of arenes

山口潤一郎

Gordon Research Conference “Heterocyclic Compounds”2017年06月19日

詳細

開催地:Salve Regina

Synthesis of Fully Arylated Arenes, Acenes, and Benzoheteroles

山口潤一郎

ISPAC 20172017年06月10日

Decarbonylative Coupling of Aromatic Esters

山口潤一郎

第2回精密制御反応場国際シンポジウム2017年05月12日

芳香族分子の新奇カップリング法・合成法の開発

山口潤一郎

先進研究講演会2017年04月22日

芳香族分子の新奇カップリング法・合成法の開発

山口潤一郎

向研会ドクター会2017年03月15日

Aromatic Molecules: Decarbonylative Coupling and Multiple Arylation

山口潤一郎

第七回日中若手化学者フォーラム2017年03月18日

化学情報伝達・啓発のためのウェブシステムの構築 化学ポータルサイトChem-Station

山口潤一郎

化学工学会・年会2017年03月06日

結合切断反応が拓く革新的分子合成技術の開発

山口潤一郎

武田薬品工業講演会2016年12月15日

Webサイトによる情報発信・ケムステーションの運営

山口潤一郎

CSJ化学フェスタ2016年11月14日

学内研究制度

特定課題研究

マルチアレーン・アセン化合物のプログラム合成法の開発

2016年度

研究成果概要:芳香族化合物群は、機能性分子における最重要骨格のひとつである。特にアリール基で置換された芳香族化合物群は、光電子機能性材料や生体機能性材料に頻繁に見られる。導入するアリール基の性質に起因して分子全体の構造あるいは電子的性質は大きく...芳香族化合物群は、機能性分子における最重要骨格のひとつである。特にアリール基で置換された芳香族化合物群は、光電子機能性材料や生体機能性材料に頻繁に見られる。導入するアリール基の性質に起因して分子全体の構造あるいは電子的性質は大きく変化するため、分子の機能を発現する上でアリール基は重要な役割を担っている。そのため、アリール基を芳香族化合物に自在に導入することが出来れば、分子の機能を自在に操ることが可能となる。我々は既にチオフェンやチアゾールが有するC–H結合を望みの位置かつ望みの様式でアリール基に変換することで、アリール化された5員環芳香族ヘテロ環の自在合成を可能としてた。また、得られた5員環からの環変換反応によりアリール基がすべて異なるヘキサアリールベンゼン、ヘキサアリールピリジンの合成を達成してた。さらに、アリール化された5員環ヘテロ芳香族化合物の環変換反応により、マルチアリール化アセン・ヘテロールの自在合成法を開発した。

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科目名開講学部・研究科開講年度学期
理工学基礎実験2B 応化先進理工学部2017秋学期
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有機化学基礎実験先進理工学部2017秋学期
有機化学基礎実験  【前年度成績S評価者用】先進理工学部2017秋学期
有機化学実験先進理工学部2017秋学期
有機化学実験  【前年度成績S評価者用】先進理工学部2017秋学期
応用化学総論先進理工学部2017春学期
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応用化学専門演習先進理工学部2017秋学期
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工業化学実験I先進理工学部2017秋学期
工業化学実験I  【前年度成績S評価者用】先進理工学部2017秋学期
卒業論文先進理工学部2017通年
卒業論文  【前年度成績S評価者用】先進理工学部2017通年
工業化学実験II先進理工学部2017春学期
工業化学実験II  【前年度成績S評価者用】先進理工学部2017春学期
有機金属化学先進理工学部2017春学期
有機金属化学先進理工学部2017春学期
有機反応論先進理工学部2017秋学期
有機反応論先進理工学部2017秋学期
工業化学先進理工学部2017秋学期
機器分析演習先進理工学部2017秋学期
上級有機化学A先進理工学部2017春学期
Industrial Chemistry先進理工学部2017春学期
Graduation Thesis A先進理工学部2017秋学期
修士論文(応化)大学院先進理工学研究科2017通年
Research on Synthetic Organic Chemistry大学院先進理工学研究科2017通年
有機合成化学研究大学院先進理工学研究科2017通年
Advanced Organic Chemistry A大学院先進理工学研究科2017春学期
有機化学特論A大学院先進理工学研究科2017春学期
生物有機化学特論大学院先進理工学研究科2017春クォーター
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応用化学特別実験大学院先進理工学研究科2017通年
特定課題演習・実験大学院先進理工学研究科2017通年
Seminar on Advanced Molecular Design A大学院先進理工学研究科2017春学期
分子設計学演習A大学院先進理工学研究科2017春学期
Seminar on Advanced Molecular Design B大学院先進理工学研究科2017秋学期
分子設計学演習B大学院先進理工学研究科2017秋学期
Master's Thesis (Department of Applied Chemistry)大学院先進理工学研究科2017通年
有機合成化学研究大学院先進理工学研究科2017通年
実践的化学知演習A大学院先進理工学研究科2017通年
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