前川 智弘 (マエガワ トモヒロ)

  • 薬学部 創薬科学科 教授/創薬科学科長
Last Updated :2024/02/02

コミュニケーション情報 byコメンテータガイド

  • コメント

    有機化学を基盤とした医薬品化学に関する研究をしています。医薬品を開発する上で有用な有機化学反応の開発も行っています。

研究者情報

学位

  • 博士(薬学)(大阪大学)

ホームページURL

ORCID ID

J-Global ID

研究キーワード

  • 環境調和型反応   複素環   有機合成化学   catalytic reaction   synthetic organic chemistry   

現在の研究分野(キーワード)

    有機化学を基盤とした医薬品化学に関する研究をしています。医薬品を開発する上で有用な有機化学反応の開発も行っています。

研究分野

  • ライフサイエンス / 薬系化学、創薬科学

経歴

  • 2019年04月 - 現在  近畿大学薬学部 医薬品化学研究室教授
  • 2013年04月 - 2019年03月  近畿大学薬学部 医薬品化学研究室准教授
  • 2009年01月 - 2013年03月  大阪大学大学院薬学研究科特任准教授
  • 2007年10月 - 2008年12月  岐阜薬科大学薬品化学研究室講師
  • 2007年04月 - 2007年09月  岐阜薬科大学薬品化学研究室助教
  • 2003年04月 - 2007年03月  岐阜薬科大学薬品化学研究室助手

学歴

  •         - 2003年   大阪大学   薬学研究科   分子薬科学専攻
  •         - 2003年   大阪大学   Graduate School, Division of Pharmaceutical Sciences
  •         - 1998年   名古屋大学   工学部   応用化・物質化学科
  •         - 1998年   名古屋大学   Faculty of Engineering

所属学協会

  • ヨウ素学会   日本プロセス化学会   有機合成化学協会   アメリカ化学会   日本薬学会   The Society of Synthetic Organic Chemistry, Japan   The Pharmaceutical Society of Japan   

研究活動情報

論文

  • Junpei Matsuoka; Yuna Yano; Yuuka Hirose; Koushi Mashiba; Nanako Sawada; Akira Nakamura; Tomohiro Maegawa
    The Journal of Organic Chemistry 89 1 770 - 777 2023年12月
  • Akira Nakamura; Jyunya Morimoto; Maho Taniguchi; Haruka Aoyama; Jiadong He; Tomohiro Maegawa
    Tetrahedron Letters 126 154656 - 154656 2023年08月
  • Tomohiro Maegawa; Akira Nakamura; Tohko Kine; Haruna Uenishi; Yuri Maki; Yasuhito Kase; Mayo Takagi
    Synlett 34 11 1253 - 1258 2023年02月 
    Abstract We have developed a regioselective synthesis of 3,4-disubstituted isoxazoles by using a chalcone-rearrangement strategy. The reaction of β-ketoacetals with hydroxylamine hydrochloride and pyridine afforded the corresponding 3,4-disubstituted isoxazoles via isoxazolines or oximes. Depending on the substrate, another disubstituted isomer was also obtained under our optimized conditions, and a reaction mechanism for each transformation is proposed.
  • Akira Nakamura; Fei Rao; Kazuchika Ukiya; Riko Matsunaga; Shin-ichiro Ohira; Tomohiro Maegawa
    Organic & Biomolecular Chemistry 21 6 1134 - 1137 2023年 
    Herein we present a simple and efficient method for the synthesis of thioaurones (hemithioindigos) from MOM-protected 2′-mercaptochalcones with NBS and pyridine.
  • Tomohiro Maegawa; Yasuyoshi Miki; Ryohei Oishi; Ayumi Maekawa; Kazutoshi Segi; Hiromi Hamamoto; Akira Nakamura
    Synthesis 54 18 4095 - 4103 2022年09月 
    Abstract We investigated the reaction of ketoximes with hypervalent iodine reagents. A combination of PhI(OAc)2 and BF3·Et2O promoted the Beckmann rearrangement of ketoximes, thus yielding the corresponding amides. From a detailed investigation of the reaction, we determined that the Beckmann rearrangement is preceded by acetylation of the hydroxy group of the ketoxime in situ, accelerating the Beckmann rearrangement. We confirmed that the acetylated ketoxime undergoes the Beckmann rearrangement with BF3·Et2O. The reaction of ketoximes with Koser’s reagent [PhI(OH)OTs] in the presence of tetrahydrofuran results in hydrolysis, affording the corresponding ketones in high yields at room temperature.
  • Akira Nakamura; Akira Imamiya; Yuichiro Ikegami; Fei Rao; Harumi Yuguchi; Yasuyoshi Miki; Tomohiro Maegawa
    RSC Advances 12 47 30426 - 30431 2022年 
    A method for the highly selective synthesis of two benzofuran isomers, 3-formylbenzofurans and 3-acylbenzofurans, by rearranging and subsequently transforming 2-hydroxychalcones has been developed.
  • Akira Nakamura; Kouhei Yamamoto; Ryo Murakami; Norihito Kawashita; Kouichi Matsumoto; Tomohiro Maegawa
    Synthesis 53 20 3862 - 3868 2021年06月 [査読有り]
     
    A method for synthesizing six-membered heterocyclic compounds was developed based on the features of O,P-acetals. Sequential reactions of intramolecular cyclization between the methylene carbon atom of O,P-acetal and its electrophilic functional group (ester or protected carbamate) was followed by Horner-Wadsworth-Emmons (HWE) olefination with various aldehydes. The developed one-pot method yielded isochroman-4-one and benzoxazin-3-one derivatives with an alkylidene moiety.
  • Makoto Sako; Keigo Higashida; Ganesh Tatya Kamble; Kevin Kaut; Ankit Kumar; Yuka Hirose; Da-Yang Zhou; Takeyuki Suzuki; Magnus Rueping; Tomohiro Maegawa; Shinobu Takizawa; Hiroaki Sasai
    Organic Chemistry Frontiers 8 17 4878 - 4885 2021年 [査読有り]
     
    The catalytic enantioselective oxidative hetero-coupling of arenols using a chiral vanadium(v) complex has been developed.
  • Tomohiro Maegawa; Kana Yoshikawa; Takanori Tabata; Kazuma Fujimura; Natsumi Kuraoka; Akira Nakamura; Yasuyoshi Miki
    HETEROCYCLES 103 2 1031 - 1031 2021年 [査読有り]
  • Akira Nakamura; Kazuki Mimaki; Ken-ichi Tanigami; Tomohiro Maegawa
    Frontiers in Chemistry 8 Article 187  2020年03月 [査読有り]
  • Yuuka Hirose; Mirai Yamazaki; Misa Nogata; Akira Nakamura; Tomohiro Maegawa
    The Journal of Organic Chemistry 84 11 7405 - 7410 2019年06月
  • Dehydroxymethyl Bromination of Alkoxybenzyl Alcohols by Using a Hypervalent Iodine Reagent and Lithium Bromide
    Shibata, Ayako; Kitamoto, Sara; Fujimura, Kazuma; Hirose, Yuuka; Hamamoto, Hiromi; Nakamura, Akira; Miki, Yasuyoshi; Maegawa, Tomohiro
    Synlett 29 2275 - 2278 2018年08月 [査読有り]
  • Constraction of azaisoflavone derivatives by hypervalent iodine reagent-mediated oxidative rearrangement of 2'-nitrochalcone
    Akira Nakamura; Reo Takane; Junki Tanaka; Junya Morimoto; Tomohiro Maegawa
    Heterocycles 97 785 - 792 2018年05月 [査読有り]
  • Direct Synthesis of Chalcones from Anilides with Phenyl Vinyl Ketones by Oxidative Coupling through C-H Bond Activation
    Maegawa, Tomohiro; Mizui, Ryota; Urasaki, Miki; Fujimura, Kazuma; Nakamura, Akira; Miki, Yasuyoshi
    ACS Omega 3 5375 - 5381 2018年05月 [査読有り]
  • Hypervalent Iodine-Mediated Beckmann Rearrangement of Ketoximes
    Oishi, Ryohei; Segi, Kazutoshi; Hamamoto, Hiromi; Nakamura, Akira; Maegawa, Tomohiro; Miki, Yasuyoshi
    Synlett 29 1465 - 1468 2018年03月 [査読有り]
  • Akira Nakamura; Hodaka Kanou; Junki Tanaka; Akira Imamiya; Tomohiro Maegawa; Yasuyoshi Miki
    Organic and Biomolecular Chemistry 16 4 541 - 544 2018年 [査読有り]
     
    A mild oxidation method for the conversion of aldoximes to carboxylic acids was developed mediated by hypervalent iodine reagents. This method covers a wide range of functionalized aldoximes and proceeds under mild conditions, utilizing PhI(OH)OTs as an oxidant.
  • Yasunari Monguchi; Masahiro Mizuno; Tomohiro Ichikawa; Yuki Fujita; Eri Murakami; Tomohiro Hattori; Tomohiro Maegawa; Yoshinari Sawama; Hironao Sajiki
    JOURNAL OF ORGANIC CHEMISTRY 82 20 10939 - 10944 2017年10月 [査読有り]
     
    In the presence of palladium on carbon (Pd/C) as a catalyst, hydrogenation of aliphatic nitriles in cyclohexane efficiently proceeded at 25-60 degrees C under ordinary hydrogen gas pressure to afford the corresponding tertiary amines. However, the use of rhodium on carbon (Rh/C) led to the highly selective generation of secondary amines. Hydrogenation of aromatic nitriles and cyclohexanecarbonitrile selectively produced secondary amines in the presence of either Pd/C or Rh/C.
  • Reiya Ohta; Yuichi Kuboki; Yuki Yoshikawa; Yasuyuki Koutani; Tomohiro Maegawa; Hiromichi Fujioka
    JOURNAL OF FLUORINE CHEMISTRY 201 1 - 6 2017年09月 [査読有り]
     
    A versatile and chemoselective route has been developed for the synthesis of aliphatic fluorinated methyl ethers (ROCH2RF), specifically monofluoromethyl ethers (ROCH2F) and trifluoromethylthiomethyl ethers (ROCH2SCF3), through pyridinium-type salt intermediates derived from methoxymethyl (MOM) ethers. The addition of a fluorine source (F- or SCF3-) to the pyridinium-type salts afforded the corresponding fluorinated methyl ethers in good yields under mild conditions. Notably, the synthesis of monofluoromethyl ethers proceeded within just 5 min.
  • Akira Nakamura; Satoshi Tanaka; Akira Imamiya; Reo Takane; Chiaki Ohta; Kazuma Fujimura; Tomohiro Maegawa; Yasuyoshi Miki
    ORGANIC & BIOMOLECULAR CHEMISTRY 15 32 6702 - 6705 2017年08月 [査読有り]
     
    An efficient one-pot method was developed for the construction of 3-acylindoles via oxidative rearrangement of 2-aminochalcones followed by intramolecular cyclization. The reaction was used to convert a variety of 2-aminochalcones into 3-acylindoles in moderate to high yields.
  • 前川智弘; 野方美沙; 廣瀬優香; 大上峻; 中村光; 三木康義; 藤岡弘道
    Journal of Organic Chemistry 82 14 7608 - 7613 2017年07月 [査読有り]
     
    A novel transformation reaction of methylene acetals, using a combination of trimethyl(phenylthio)silane (PhSTMS) and N-bromosuccinimide (NBS) under mild reaction conditions, is described. Various methylene acetals were converted to their corresponding bromoformates in good to high yields. Under the given conditions, the reaction proceeded via a radical pathway. Further transformation of bromoformates to their corresponding epoxides was achieved by treatment with NaOMe.
  • Yasuyoshi Miki; Yukari Hirata; Noriko Makino; Yuuka Hirose; Misa Nogata; Akira Nakamura; Hiromi Hamamoto; Tomohiro Maegawa
    HETEROCYCLES 94 7 1269 - 1279 2017年07月 [査読有り]
     
    We studied selective bromination and iodination of dimethyl indole-2,3-dicarboxylates using phenyliodine diacetate (PIDA), LiBr, and LiI in the presence of Lewis acid. The protective group on the nitrogen of indole is important for selectivity of the halogenation position, and the use of a benzenesulfonyl group as a protective group resulted in preferential halogenation of indole at the 6-position.
  • Tomohiro Maegawa; Misa Nogata; Takaya Honda; Akira Nakamura; Yasuyoshi Miki
    HETEROCYCLES 95 1 608 - 614 2017年01月 [査読有り][招待有り]
     
    A novel approach to producing the quinoline skeleton from 2-aminochalcone was developed. Treatment of benzyloxycarbonyl (Cbz)-protected 2-aminochalcones with BF3 center dot Et2O afforded quinoline derivatives via the deprotection of the Cbz group and isomerization of olefin in a one-pot reaction. The reaction of various 2-aminochalcones proceeded to give the corresponding 2-arylquinoline derivatives in good yields. This method is applicable to the rapid synthesis of dubamine.
  • Hiromi Hamamoto; Hideaki Umemoto; Misako Umemoto; Chiaki Ohta; Emi Fujita; Akira Nakamura; Tomohiro Maegawa; Yasuyoshi Miki
    HETEROCYCLES 91 3 561 - 572 2015年03月 [査読有り]
     
    Hypervalent iodine mediated decarboxylative halogenation of indoledicarboxylic acid derivatives was studied. The treatment of 1-methylindole-2,3-dicarboxylic acid with phenyliodine diacetate (PIDA) in the presence of lithium bromide gave 1-methyl-3,3-bromooxindole. However, the reaction of 1-(phenylsulfonyl)indole-2,3-dicarboxylic acid with PIDA in the presence of lithium bromide afforded 2,3-dibromo-1-(phenylsulfonyl)indole. In a similar manner, the 2,3-dichloro- and 2,3-diiodoindole derivatives could be obtained by the reaction of the indole-2,3-dicarboxylic acids with PIDA in the presence of lithium chloride and iodide. This method was optimized to the synthesis of polybromoindole alkaloids.
  • Hideaki Umemoto; Takuya Onaka; Yasuyoshi Miki; Akira Nakamura; Tomohiro Maegawa
    SYNLETT 26 2 205 - 208 2015年01月 [査読有り]
     
    The reaction of 2-[(trimethylsilyl) methyl]-2H-tetrazoles with various alkyl halides and carbonates using n-butyllithium or lithium diisopropylamide (LDA) gave 2-[1-(trimethylsilyl) alkyl]-2H-tetrazoles and (2H-tetrazol-2-yl) acetates as useful synthons of modified tetrazoles.
  • Hideaki Umemoto; Takuya Onaka; Yasuyoshi Miki; Akira Nakamura; Tomohiro Maegawa
    HETEROCYCLES 89 11 2545 - 2553 2014年11月 [査読有り]
     
    2-((Trimethylsilyl)methyl)-2H-tetrazoles were treated with aldehydes and ketones in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) to give 2-(2-hydroxyethyl)-2H-tetrazoles. This simple procedure offers a valuable strategy for the preparation of 2-(hydroxyethyl)-2H-tetrazoles.
  • Onaka T; Umemoto H; Miki Y; Nakamura A; Maegawa T
    The Journal of organic chemistry 79 14 6703 - 6707 2014年07月 [査読有り]
     
    A mild and regioselective 2-arylation of 5-substituted tetrazoles is described. The reaction proceeds regioselectively with a variety of arylboronic acids in the presence of [Cu(OH)(TMEDA)](2)Cl-2 to afford 2,5-disubstituted tetrazoles. This is the first report of highly regioselective arylation of 5-alkyltetrazoles.
  • Yoshiaki Kitamura; Kazumi Taniguchi; Tomohiro Maegawa; Yasunari Monguchi; Yukio Kitade; Hironao Sajiki
    HETEROCYCLES 88 1 233 - 243 2014年01月 [査読有り]
     
    We have developed an environmentally friendly and highly efficient solvent-free Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction using a polymer-supported copper catalyst (Cu/HP20). Substrates poorly soluble in common organic solvents are also applicable to the present cycloaddition reaction without any solvents and provide the corresponding 1,4-triazole in high yields.
  • Tomohiro Maegawa; Hiromichi Fujioka
    JOURNAL OF SYNTHETIC ORGANIC CHEMISTRY JAPAN 71 7 694 - 705 2013年07月 [査読有り]
     
    Although acetals are useful protective groups for carbonyl functions and widely used in organic synthesis, their protection and deprotection under acidic conditions unable to use the substrates with acid labile functions. We recently found that the combination of TESOTf (Et3Si0Tf) 2,6lutidine or 2,4,6-collidine was effective for the deprotection of acetal. The reaction proceeded under nearly neutral conditions and was applicable to the substrates with acid labile functions, and the most noteworthy of this method is the achievement of the chemoselective deprotection of acetals in the presence of ketals. The above reaction proceeds via pyridinium-type salt intermediates, which are found to be highly reactive toward various nucleophiles not only H20 but also heteroatom and carbon nucleophiles affording the corresponding substituted products. This reaction could be conducted under mild reaction conditions whereas conventional methods need harsh reaction conditions. This methodology is also applicable to the deprotection of acetal-type protective groups such as MOM-type ethers, THP ether, and methylene acetal, and the combination of TMSOTf (TESOTf) 2,2'-bipyridyl afforded the best result
  • Tomohiro Maegawa; Yasuyuki Koutani; Kazuki Otake; Hiromichi Fujioka
    Journal of Organic Chemistry 78 7 3384 - 3390 2013年04月 [査読有り]
     
    A mild and efficient method for formation of methylene acetals from 1,2- and 1,3-diols using methoxymethylphenylsulfide, 1,3-dibromo-5,5- dimethylhydantoin (DBDMH), and dibutylhydroxytoluene (BHT) is described. The use of BHT in this process suppresses side reactions and enables high-yielding formation of methylene acetals of various diols, including carbohydrate-type substrates. © 2013 American Chemical Society.
  • 荒井 孝義; 前川 智弘; 藤岡 弘道; 佐藤 敏文; 山本 靖典
    有機合成化学協会誌 71 7 731 - 731 The Society of Synthetic Organic Chemistry, Japan 2013年
  • Takahashi Tohru; Yoshimura Masatoshi; Suzuka Hiroyasu; Maegawa Tomohiro; Sawama Yoshinari; Monguchi Yasunari; Sajiki Hironao
    TETRAHEDRON 68 39 8293 - 8299 2012年09月 [査読有り]
  • Goto A; Otake K; Kubo O; Sawama Y; Maegawa T; Fujioka H
    Chemistry (Weinheim an der Bergstrasse, Germany) 18 36 11423 - 11432 2012年09月 [査読有り]
     
    The effects of phosphorus substituents on the reactivity of alpha-alkoxyphosphonium salts with nucleophiles has been explored. Reactions of a-alkoxyphosphonium salts, prepared from various acetals and tri(o-tolyl)-phosphine, with a variety of nucleophiles proceeded efficiently. These processes represent the first examples of high-yielding nucleophilic substitution reactions of a-alkoxyphosphonium salts. The reactivity of these salts was determined by a balance between steric and electronic factors, respectively, represented by cone angles theta and CO stretching frequencies nu (steric and electronic parameters, respectively). In addition, a novel reaction of a-alkoxyphosphonium salts derived from Ph3P with Grignard reagents was observed to take place in the presence of O-2 to afford alcohols in good yields. A radical mechanism is proposed for this process that has gained support from isotope-labeling and radical-inhibition experiments.
  • Maegawa T; Otake K; Hirosawa K; Goto A; Fujioka H
    Organic letters 14 18 4798 - 4801 2012年09月 [査読有り]
     
    Highly substituted four- and five-membered heterocycles were prepared starting with O,P- and N,P-acetals by using a one-pot method involving base induced cyclization and a Horner-Wadsworth-Emmons (HWE) olefination reaction. Divergent synthesis of various heterocycles was achieved by using this method and transformations of the alkenyl group in the products of these processes were exemplified. Finally, a short and efficient synthesis of (+/-)-pseudodeflectusin based on the new methodology was achieved.
  • Yutaka Minamitsuji; Atsuhisa Kawaguchi; Ozora Kubo; Yoshifumi Ueyama; Tomohiro Maegawa; Hiromichi Fujioka
    ADVANCED SYNTHESIS & CATALYSIS 354 10 1861 - 1866 2012年07月 [査読有り]
     
    A mild and divergent route for the synthesis of alkyl ethers from methoxymethyl (MOM) and methoxyethyl (ME) ether derivatives via pyridinium-type salt intermediates has been developed. The addition of organocuprates to the salts afforded the corresponding alkyl ethers, including highly crowded ones, in high yields even in the presence of acid- or base-sensitive functional groups.
  • Sawama Yoshinari; Yabe Yuki; Shigetsura Masahiro; Yamada Tsuyoshi; Nagata Saori; Fujiwara Yuta; Maegawa Tomohiro; Monguchi Yasunari; Sajiki Hironao
    ADVANCED SYNTHESIS & CATALYSIS 354 5 777 - 782 2012年03月 [査読有り]
  • Hiromichi Fujioka; Kenzo Yahata; Tomohito Hamada; Ozora Kubo; Takashi Okitsu; Yoshinari Sawama; Takuya Ohnaka; Tomohiro Maegawa; Yasuyuki Kita
    CHEMISTRY-AN ASIAN JOURNAL 7 2 367 - 373 2012年02月 [査読有り]
     
    Mild substitution reactions of acetals with carbon nucleophiles via the pyridinium-type salts generated by the treatment of acetals with TESOTf-2,4,6-collidine or 2,2'-bipyridyl have been developed. Various carbon nucleophiles, such as organocuprates, silyl enol ethers, enamines, etc., reacted with the pyridinium-type salts to give the corresponding substituted products in good yields. The reactions proceeded under very mild conditions (non-acidic conditions) and thus acid-sensitive functional groups can be tolerated during the reaction. In addition, only an acetal can form the pyridinium-type salt and react with nucleophiles in the presence of a ketal. This unusual selectivity is in contrast to general methods conducted under acidic conditions.
  • Nkaelang Modutlwa; Hiroyuki Tada; Yoshiki Sugahara; Koichi Shiraki; Nobuyuki Hara; Yoshihiro Deyashiki; Tomohiro Maegawa; Yasunari Monguchi; Hironao Sajiki
    HETEROCYCLES 84 1 419 - 429 2012年01月 [査読有り]
     
    N-6-Benzyladenine (benzyladenine), a plant growth regulator, was efficiently deuterated by the hydrogen deuterium (H D) exchange reaction catalyzed by palladium on carbon-ethylenediamine complex [Pd/C(en)], while use of palladium on carbon (Pd/C) as a catalyst led to a low deuterium incorporation at room temperature or complete removal of the N-6-benzyl group at 110 degrees C or higher temperature. The obtained benzyladenine-d(5) was used as an internal standard (surrogate) for the quantification of residual benzyladenine in fruits, vegetables, cereals, and beans using LC/MS/MS. Satisfactory recovery of benzyladenine between 94.2 and 105.7% (100.4% on the average) was obtained. The agrochemical could be detected within the concentration range of 0.25-0.50 ng/g in agricultural products using the present quantification method.
  • Maegawa T; Koutani Y; Senami K; Yahata K; Fujioka H
    Heterocycles 86 1 455 - 467 2012年 [査読有り]
  • Takashi Ikawa; Yuki Fujita; Tomoteru Mizusaki; Sae Betsuin; Haruki Takamatsu; Tomohiro Maegawa; Yasunari Monguchi; Hironao Sajiki
    ORGANIC & BIOMOLECULAR CHEMISTRY 10 2 293 - 304 2012年 [査読有り]
     
    Nitriles were found to be highly effective alkylating reagents for the selective N-alkylation of amines under catalytic hydrogenation conditions. For the aromatic primary amines, the corresponding secondary amines were selectively obtained under Pd/C-catalyzed hydrogenation conditions. Although the use of electron poor aromatic amines or bulky nitriles showed a lower reactivity toward the reductive alkylation, the addition of NH4OAc enhanced the reactivity to give secondary aromatic amines in good to excellent yields. Under the same reaction conditions, aromatic nitro compounds instead of the aromatic primary amines could be directly transformed into secondary amines via a domino reaction involving the one-pot hydrogenation of the nitro group and the reductive alkylation of the amines. While aliphatic amines were effectively converted to the corresponding tertiary amines under Pd/C-catalyzed conditions, Rh/C was a highly effective catalyst for the N-monoalkylation of aliphatic primary amines without over-alkylation to the tertiary amines. Furthermore, the combination of the Rh/C-catalyzed N-monoalkylation of the aliphatic primary amines and additional Pd/C-catalyzed alkylation of the resulting secondary aliphatic amines could selectively prepare aliphatic tertiary amines possessing three different alkyl groups. According to the mechanistic studies, it seems reasonable to conclude that nitriles were reduced to aldimines before the nucleophilic attack of the amine during the first step of the reaction.
  • Amos B. Smith; Shuzhi Dong; Richard J. Fox; Jehrod B. Brenneman; John A. Vanecko; Tomohiro Maegawa
    TETRAHEDRON 67 51 9809 - 9828 2011年12月 [査読有り]
     
    An effective, asymmetric total synthesis of the antibiotic (+)-sorangicin A (1) has been achieved. Central to this venture was the development of first- and second-generation syntheses of the signature dioxabicyclo[3.2.1]octane core, the first featuring chemo- and stereoselective epoxide ring openings facilitated by a Co-2(Co)(6)-alkyne complex, the second involving a KHMDS-promoted epoxide ring formation/opening cascade. Additional highlights include effective construction of the dihydro- and tetrahydropyran ring systems, respectively, via a stereoselective conjugate addition/alpha-oxygenation protocol and a thioketalization/hydrostannane reduction sequence. Late-stage achievements entailed two Julia-Kocienski olefinations to unite three advanced fragments with high E-stereoselectivity, followed by a modified Stille protocol to introduce the Z,Z,E trienoate moiety, thereby completing the carbon skeleton. Mukaiyama macrolactonization, followed by carefully orchestrated Lewis and protic acid-promoted deprotections that suppressed isomerization and/or destruction of the sensitive (Z,Z,E)-trienoate linkage completed the first, and to date only, total synthesis of (+)-sorangicin A (1). (C) 2011 Elsevier Ltd. All rights reserved.
  • Yasunari Monguchi; Yuki Fujita; Shota Hashimoto; Mariko Ina; Tohru Takahashi; Ryo Ito; Kei Nozaki; Tomohiro Maegawa; Hironao Sajiki
    TETRAHEDRON 67 45 8628 - 8634 2011年11月 [査読有り]
     
    The solvent-free and solid-phase hydrogenation of various reducible functionalities was efficiently catalyzed by heterogeneous palladium on carbon (Pd/C) under ambient hydrogen pressure and temperature. The Pd/C-catalyzed Suzuki-Miyaura coupling reaction between solid aryl bromides and solid arylboronic acids to generate the corresponding solid biaryls was also achieved under the totally solid-phase conditions. (C) 2011 Elsevier Ltd. All rights reserved.
  • Yuta Fujiwara; Youhei Iwasaki; Tomohiro Maegawa; Yasunari Monguchi; Hironao Sajiki
    CHEMCATCHEM 3 10 1624 - 1628 2011年10月 [査読有り]
     
    An efficient and practical procedure for the hydrogenation of aliphatic and aromatic ketones under mild reaction conditions is established. The method is highly effective even for the hydrogenation of sterically hindered ketones. Furthermore, the selective hydrogenation of the carbonyl group of aromatic ketones was achieved with the aromatic nuclei and the resulting secondary benzyl alcohol moiety still intact on addition of catalytic amount of pyridine.
  • Tomohiro Maegawa; Kazuki Otake; Akihiro Goto; Hiromichi Fujioka
    ORGANIC & BIOMOLECULAR CHEMISTRY 9 16 5648 - 5651 2011年 [査読有り]
     
    A new direct conversion of O,O-acetals to esters via O,P-acetal intermediates was developed. The regioselective cleavage of unsymmetrical cyclic acetals occurred to give the more crowded esters as single isomers.
  • Ozora Kubo; Kenzo Yahata; Tomohiro Maegawa; Hiromichi Fujioka
    CHEMICAL COMMUNICATIONS 47 32 9197 - 9199 2011年 [査読有り]
     
    A diastereoselective ring contraction of the diastereomixture of 2,4-disubstituted 1,3-dioxepins to 2,5-cis-2,3,5-trisubstituted tetrahydrofurans was achieved using TfOH in DMF. The reaction appears to proceed via a chair-like transition state, in which stereomutation of the oxocarbenium occurred, followed by an aldol-type cyclization.
  • Fujioka H; Goto A; Otake K; Kubo O; Sawama Y; Maegawa T
    Chemical communications (Cambridge, England) 47 35 9894 - 9896 2011年 [査読有り]
     
    An unusual and novel reaction of alpha-alkoxyphosphonium salts, generated from O,O-acetals and Ph3P, with Grignard reagents under an O-2 atmosphere afforded alcohols in moderate to high yields. It was clarified by isotopic labelling experiments that the reaction proceeded via a novel radical pathway.
  • Hiromichi Fujioka; Kenzo Yahata; Ozora Kubo; Yoshinari Sawama; Tomohito Hamada; Tomohiro Maegawa
    ANGEWANDTE CHEMIE-INTERNATIONAL EDITION 50 51 12232 - 12235 2011年 [査読有り]
  • Tohru Takahashi; Yusuke Iida; Yuta Fujiwara; Yuya Inagaki; Tomohiro Maegawa; Yasunari Monguchi; Hironao Sajiki
    ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY 239 2010年03月
  • Hetero-Suzuki-Miyaura Cross-Coupling Using Palladium on Carbon
    Kitamura Yoshiaki; Sako Satoko; Tsutsui Azusa; Monguchi Yasunari; Maegawa Tomohiro; Kitade Yukio; Sajiki Hironao
    Synfacts 7 844 - 844 GEORG THIEME VERLAG KG 2010年
  • LC-MS/MSを用いたクロバザムとその代謝物であるN-デスメチルクロバザムの高速及び高感度なハイスループット分析
    谷口 和美; 中村 光浩; 大森 智史; 門口 泰也; 前川 智弘; 井口 和弘; 伊藤 善規; 臼井 茂之; 佐治木 弘尚; 平野 和行
    日本薬学会年会要旨集 129年会 4 100 - 100 2009年03月
  • Akiko Ido; Shinji Ishihara; Ryota Kobayashi; Akira Kume; Tomohiro Maegawa; Yasunari Monguchi; Sueo Wada; Hironao Sajiki; Hisamitsu Nagase
    ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY 237 2009年03月 [査読有り]
  • Yasunari Monguchi; Akira Kume; Shinji Ishihara; Sueo Wada; Tomohiro Maegawa; Hisamitsu Nagase; Hironao Sajiki
    ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY 237 2009年03月 [査読有り]
  • Shinji Ishihara; Akiko Ido; Tomohiro Maegawa; Yasunari Monguchi; Sueo Wada; Hisamitsu Nagase; Hironao Sajiki
    ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY 237 2009年03月 [査読有り]
  • Nkaelang Modutlwa; Hiroyuki Tada; Yoshiki Sugahara; Koichi Shiraki; Nobuyuki Hara; Yoshihiro Deyashiki; Takayuki Ando; Tomohiro Maegawa; Yasunari Monguchi; Hironao Sajiki
    Nucleic acids symposium series (2004) 53 105 - 106 2009年 [査読有り]
     
    Palladium on carbon-ethylenediamine complex [Pd/C(en)] catalyzed deuteration of N(6)-benzyladenine-d(5), which is a plant growth regulator, to introduce 5 deuterium atoms, while use of Pd/C as a catalyst led to a complete removal of N(6)-benzyl group. The corresponding deuterated N(6)-benzyladenine was successfully used as a surrogate compound for the quantitative analysis of residual benzyladenine in crops using LC/MS/MS.
  • Akinori Mori; Tomoteru Mizusaki; Masami Kawase; Tomohiro Maegawa; Yasunari Monguchi; Shinobu Takao; Yukio Takagi; Hironao Sajiki
    ADVANCED SYNTHESIS & CATALYSIS 350 3 406 - 410 2008年02月 [査読有り]
     
    A diphenyl sulfide immobilized on palladium-on-carbon system, Pd/C[Ph(2)S], was developed to achieve the highly chemoselective hydrogenation of alkenes, acetylenes, azides, and nitro groups in the presence of aromatic ketones, halides, benzyl esters, and N-Cbz protective groups. Instrumental analyses of the heterogeneous catalyst demonstrated that diphenyl sulfide was embedded on Pd/C via coordination of its sulfur atom to palladium metal or physical interaction with graphite layers of the activated carbon. The catalyst could be recovered and reused at least five times without any significant loss of the reactivity.
  • Nobuhiro Ito; Hiroyoshi Esaki; Tsuneaki Maesawa; Eikoh Imamiya; Tomohiro Maegawa; Hironao Sajiki
    BULLETIN OF THE CHEMICAL SOCIETY OF JAPAN 81 2 278 - 286 2008年02月 [査読有り]
     
    An effective and applicable deuteration method for aromatic rings using Pt/C-D2O-H-2 system was established. Especially, phenol was fully deuterated even at room temperature, and other electron-rich aromatic nuclei were efficiently deuterated under mild conditions. The scope and limitations of the presence method and its application to the synthesis of deuterium-labeled biologically active compounds and deuterium-labeled building blocks for practical multi-gram scale syntheses are reported.
  • 門口泰也; 喜多村徳昭; 前川智弘; 佐治木弘尚
    ケミカルエンジニアリング 53 4 256 - 261 化学工業社 2008年
  • Mori S; Yanase T; Aoyagi S; Monguchi Y; Maegawa T; Sajiki H
    Chemistry (Weinheim an der Bergstrasse, Germany) 14 23 6994 - 6999 2008年 [査読有り]
     
    A variety of aryl iodides were coupled with aromatic and aliphatic terminal alkynes to give the corresponding 1,2-disubstituted aromatic alkynes in good yields by using only 0.4 mol % of the heterogeneous 10 % Pd/C as the catalyst without a ligand, copper salt, or amine in an aqueous medium.
  • Yoshiaki Kitamura; Satoko Sako; Takahiro Udzu; Azusa Tsutsui; Tomohiro Maegawa; Yasunari Monguchi; Hironao Sajiki
    Chemical Communications 5069 - 5071 ROYAL SOC CHEMISTRY 2007年12月 [査読有り]
     
    We have developed a mild and efficient protocol for the ligand-free and heterogeneous Pd/C-catalyzed hetero Suzuki-Miyaura coupling reaction that allows for the synthesis of both heteroaryl-aryl and heteroaryl-heteroaryl derivatives in good to excellent yields. © The Royal Society of Chemistry.
  • Takanori Kurita; Masami Abe; Tomohiro Maegawa; Yasunari Monguchi; Hironao Sajiki
    SYNLETT 16 2521 - 2524 2007年10月 [査読有り]
     
    A facile and environmentally friendly synthetic method for a variety of symmetrical 1,3-diyne derivatives based on the Pd/C-Cul-catalyzed homocoupling reaction of terminal alkynes has been developed. The reaction was efficiently catalyzed by the extrernely low loading (0.01-0.03 mol%) of Pd/C and Cul (3 mol%) in the presence of molecular oxygen (02) as an oxidant without any phosphine ligands and bases.
  • Yoshiaki Kitamura; Ai Sakurai; Takahiro Udzu; Tomohiro Maegawa; Yasunari Monguchi; Hironao Sajiki
    Tetrahedron 63 43 10596 - 10602 PERGAMON-ELSEVIER SCIENCE LTD 2007年10月 [査読有り]
     
    Heterogeneous Pd/C-catalyzed Suzuki-Miyaura cross-coupling reaction of aryl boronic esters with aryl bromides was successfully carried out in aqueous media at room temperature without the use of a ligand such as phosphine derivatives. © 2007 Elsevier Ltd. All rights reserved.
  • Tomohiro Maegawa; Yoshiaki Kitamura; Satoko Sako; Takahiro Udzu; Ai Sakurai; Asami Tanaka; Yusuke Kobayashi; Koichi Endo; Utpal Bora; Takanori Kurita; Atsushi Kozaki; Yasunari Monguchi; Hironao Sajiki
    Chemistry - A European Journal 13 20 5937 - 5943 WILEY-V C H VERLAG GMBH 2007年08月 [査読有り]
     
    A mild and efficient ligand-free Suzuki-Miyaura coupling reaction catalyzed by heterogeneous Pd/C was developed. Aryl bromides and triflates undergo the cross-coupling with aryl boronic acids in excellent yields without the presence of any additives in aqueous media at room temperature. Aryl vinyl boronic acids are also applicable to this coupling reaction and provide the trans-stilbene derivatives in high yields. The application of wet-type Pd/C to the coupling reaction was achieved without any loss of activity under aerobic conditions, and the reuse of Pd/C is feasible for a fifth run without significant loss of activity. Inductively coupled plasma (ICP) mass-spectrometric analysis of the filtrate from the reaction mixture of 4-bromonitrobenzene with phenylboronic acid demonstrated that the palladium metal hardly leached into the solution within the limits of the detector (< 1 ppm), thus suggesting that the present Suzuki-Miyaura reaction proceeded by heterogeneous catalysis. © 2007 Wiley-VCH Verlag GmbH & Co. KGaA.
  • Tomohiro Maegawa; Yuki Fujita; Ai Sakurai; Akira Akashi; Mutsumi Sato; Keiji Oono; Hironao Sajiki
    CHEMICAL & PHARMACEUTICAL BULLETIN 55 5 837 - 839 2007年05月 [査読有り]
     
    Aromatic nitriles are not only important components of natural products, pharmaceuticals, herbicides and agrochemicals but also a synthetic equivalent of various functionalities. The development of synthetic methods of aromatic nitriles have been increasing in terms of its usefulness. Since aromatic nitriles are susceptible to the hydrogenation, it has been desired for the development of chemoselective hydrogenation method with retention of nitrile groups. Pd/C is one of the most popular catalysts for hydrogenation and many of reducible functional groups such as multiple bonds, benzyl ethers, N-Cbzs, nitro groups and so on could be easily reduced under the conditions. Therefore, it is very difficult to achieve the chemoselective hydrogenation of substrates containing two or more reducible functional groups. We have found that a Pd/C catalyst formed an isolable complex with ethylenediamine (en) employed as catalytic poison, and the complex [Pd/C(en)] catalyzed chemoselective hydrogenation of a variety of reducible functionalities distinguishing O-benzyl, N-Cbz and O-TBDMS protective groups, benzyl alcohols and epoxides. In the course of these investigations, we found the aryl nitriles could survive under the Pd/C(en)-catalyzed hydrogenation conditions in THF whose choice is important for the effective suppression. This methodology could be applied to the selective hydrogenation of alkene and alkyne functionalities in the presence of aromatic nitrile.
  • Hiroyoshi Esaki; Rumi Ohtaki; Tomohiro Maegawa; Yasunari Monguchi; Hironao Sajiki
    JOURNAL OF ORGANIC CHEMISTRY 72 6 2143 - 2150 2007年03月 [査読有り]
     
    A liquid-phase redox system between secondary alcohols and ketones is described. Deuteration of either secondary alcohols or ketones using the Pd/C-H-2-D2O system gave a mixture of deuterium-labeled secondary alcohols and ketones. The results indicated that the secondary alcohol was oxidized to the corresponding ketone without oxidants under the hydrogenation conditions and the hydrogenation of the aliphatic ketone to the corresponding secondary alcohol simultaneously proceeded. Detailed mechanistic studies on the redox system as well as the H-D exchange reaction are discussed.
  • Akinori Mori; Tomoteru Mizusaki; Takashi Ikawa; Tomohiro Maegawa; Yasunari Monguchi; Hironao Sajiki
    TETRAHEDRON 63 5 1270 - 1280 2007年01月 [査読有り]
     
    We have found that phenolic hydroxyl groups were readily deoxygenated via aryl sulfonate under the Pd/C-catalyzed hydrogenation conditions in the presence of diethylamine and the method could also be applicable to the hydrodeoxygenation of morphine to afford 3-deoxy-7,8-dihydromorphine. Diethylamine is not only a scavenger of the corresponding methanesulfonic acid derivative, which is produced during the reaction progress, but also a strong promoter of the Pd/C-catalyzed reduction of aryl sulfonates. This catalyst system could provide a general method for the deoxygenation of various phenol derivatives because of its mild reaction conditions, ease of handling, and no need of particular apparatus. (c) 2006 Elsevier Ltd. All rights reserved.
  • Akinori Mori; Tomoteru Mizusaki; Takashi Ikawa; Tomohiro Maegawa; Yasunari Monguchi; Hironao Sajiki
    CHEMISTRY-A EUROPEAN JOURNAL 13 5 1432 - 1441 2007年 [査読有り]
     
    A method for the deoxygenation of phenolic hydroxy groups via aryl triflates or mesylates has been established by using a combination of Pd/C-Mg-MeOH. The addition of NH4OAc to the system markedly accelerated the reaction rate and expanded the scope of the reaction. Mechanistic studies suggested that a single-electron transfer process from the Pd-0 center to the benzene ring is involved in the reduction of aryl sulfonates and that NH4OAc works as a solubilization reagent of the Mg salt and as an accelerator of the electron transfer, thus enhancing the reaction process. Our method was also applicable to the regioselective deuteration of benzene derivatives with CH3OD as the solvent and deuterium source: the original hydroxy group could be efficiently replaced with a deuterium atom.
  • Yoshiaki Kitamura; Asami Tanaka; Mutsumi Sato; Keiji Oono; Takashi Ikawa; Tomohiro Maegawa; Yasunari Monguchi; Hironao Sajiki
    Synthetic Communication 37 22 4381 - 4388 2007年01月 [査読有り]
     
    A practical and efficient preparation method of palladium-fibroin (Pd/Fib),
    silk-fibroin-supported Pd(0) by means of sonication, has been developed. The Pd/Fib
    catalyst could be prepared within 12 h at room temperature starting from commercial
    silk-fibroin and Pd(OAc)2 in MeOH, whereas our previous preparation method required
    at least 4 days. The present improved process is applicable to a large-scale preparation
    of Pd/Fib. The Pd/Fib prepared by the present method also catalyzed chemoselective
    hydrogenation of acetylenes, olefins, and azides in the presence of aromatic ketones,
    aldehydes, and halides; N-Cbz protective groups; and benzyl esters, which are
    readily hydrogenated under the Pd/C- or Pd/C(en)-catalyzed hydrogenation
    conditions. @ 2007 Taylor & Francis Group, LLC.
  • Akinori Mori; Tornoteru Mizusaki; Yurni Miyakawa; Eri Ohashi; Tornoko Haga; Tomohiro Maegawa; Yasunari Monguchi; Hironao Sajiki
    TETRAHEDRON 62 51 11925 - 11932 2006年12月 [査読有り]
     
    While Pd/C is one of the most useful catalysts for hydrogenation, the high catalyst activity of Pd/C causes difficulty in its application to chemoselective hydrogenation between different types of reducible functionalities. In order to achieve chemoselective hydrogenation using Pd/C, we investigated catalyst poison as a controller of the catalyst activity. We found that the addition of Ph2S (diphenylsulfide) to the Pd/C-catalyzed hydrogenation reaction mixture led to reasonable deactivation of Pd/C. By the use of the Pd/C-Ph2S catalytic system, olefins, acetylenes, and azides can be selectively reduced in the coexistence of aromatic carbonyls, aromatic halides, cyano groups, benzyl esters, and N-Cbz (benzyloxycarbonyl) protecting groups. The present method is promising as a general and practical chemoselective hydrogenation process in synthetic organic chemistry. (c) 2006 Elsevier Ltd. All rights reserved.
  • Hiroyoshi Esaki; Nobuhiro Ito; Shino Sakai; Tomohiro Maegawa; Yasunari Monguchi; Hironao Sajiki
    TETRAHEDRON 62 47 10954 - 10961 2006年11月 [査読有り]
     
    A protocol of a versatile H-D exchange reaction of heterocyclic compounds catalyzed by heterogeneous Pd/C in D2O is described. The reaction of various nitrogen-containing heterocycles with 10% Pd/C (10 wt % of the substrate) under hydrogen atmosphere in D2O as a deuterium source at 110-180 degrees C for 24 h afforded the corresponding deuterated compounds with satisfactory efficiency of deuteration in moderate to excellent isolated yields. Furthermore, the Pd/C-H-2-D2O system can be extended to the direct deuteration of biologically active compounds such as sulfamethazine, which is used as a synthetic antibacterial drug for fat stocks and would be applied as a general method for the preparation of the standard materials for the analysis of residual chemicals in foods and so on. (c) 2006 Elsevier Ltd. All rights reserved.
  • Yasunari Monguchi; Akira Kume; Kazuyuki Hattori; Tomohiro Maegawa; Hironao Sajiki
    TETRAHEDRON 62 33 7926 - 7933 2006年08月 [査読有り]
     
    A mild and efficient one-pot procedure for the hydrodechlorination of aromatic chlorides using a Pd/C-Et3N system was developed. A variety of aromatic chlorides could be dechlorinated at room temperature and under ambient hydrogen pressure. Et3N activates the catalysis and is likely to work as a single electron donor in this system. (c) 2006 Elsevier Ltd. All rights reserved.
  • Akinori Mori; Yumi Miyakawa; Eri Ohashi; Tomoko Haga; Tomohiro Maegawa; Hironao Sajiki
    ORGANIC LETTERS 8 15 3279 - 3281 2006年07月 [査読有り]
     
    A Pd/C-catalyzed chemoselective hydrogenation using diphenylsulfide as a catalyst poison has been developed. This methodology selectively hydrogenates olefin and acetylene functionalities without hydrogenolysis of aromatic carbonyls and halogens, benzyl esters, and N-Cbz protective groups.
  • Nobuhiro Ito; Tsutomu Watahiki; Tsuneaki Maesawa; Tomohiro Maegawa; Hironao Sajiki
    ADVANCED SYNTHESIS & CATALYSIS 348 9 1025 - 1028 2006年06月 [査読有り]
     
    We have found a synergistic effect in the H-D exchange reaction of alkyl-substituted aromatic compounds using the Pd/C-Pt/C-D2O-H-2 system. This system would lead to fully H-D exchange results even on the sterically hindered sites which were only low-deuterium incorporated by Pd/C or Pt/C independently. Since the reaction was general for a variety of aromatic compounds, it could be applied to the deuteration of dianiline derivatives as raw materials for polyimides.
  • Tomohiro Maegawa; Akira Akashi; Hironao Sajiki
    SYNLETT 9 1440 - 1442 2006年06月 [査読有り]
     
    A mild and complete hydrogenation of aromatic rings catalyzed by heterogeneous 10% Rh/C proceeds at 80 degrees C in water under 5 atm of H-2 pressure. This method is applicable to the hydrogenation of various carbon and heteroaromatic compounds such as alkylbenzenes, biphenyls, pyridines and furans.
  • H Sajiki; A Mori; T Mizusaki; T Ikawa; T Maegawa; K Hirota
    ORGANIC LETTERS 8 5 987 - 990 2006年03月 [査読有り]
     
    A Pd/C-catalyzed deoxygenation method of phenolic hydroxyl groups via aryl triflates or mesylates using Mg metal in MeOH at room temperature was developed. The addition of NH4OAc dramatically affects the reactivity and reaction rate. This method is particularly attractive to provide an environmentally benign and widely applicable removal method of phenolic alcohols under quite mild reaction conditions.
  • H Esaki; F Aoki; T Maegawa; K Hirota; H Sajiki
    HETEROCYCLES 66 361 - 369 2005年12月 [査読有り]
     
    The D-2 gas-free and base-selective H-D exchange reaction of nucleosides was developed. It discloses a convenient route to the post-synthetic incorporation of deuteriums into the base moiety of nucleic acids with high deuterium efficiency.
  • Maegawa T; Hirota K; Tatematsu K; Mori Y; Sajiki H
    The Journal of organic chemistry 70 25 10581 - 10583 2005年12月 [査読有り]
  • H Sajiki; N Ito; H Esaki; T Maesawa; T Maegawa; K Hirota
    TETRAHEDRON LETTERS 46 41 6995 - 6998 2005年10月 [査読有り]
     
    An effective and applicable Pt/C-catalyzed deuteration method of aromatic rings using D2O as a deuterium source under hydrogen atmosphere was developed. Five percent Pt/C would lead to quite effective H-D exchange results on the aromatic ring systems. The reaction is general for a variety of aromatic compounds including biologically active compounds. (c) 2005 Elsevier Ltd. All rights reserved.
  • Hironao Sajiki; Takanori Kurita; Atsushi Kozaki; Guolin Zhang; Guolin Zhang; Yoshiaki Kitamura; Tomohiro Maegawa; Kosaku Hirota
    Journal of Chemical Research 344  2005年05月

書籍

MISC

受賞

  • 2020年08月 有機合成化学協会 関西支部 第18回(2020年度)有機合成化学協会 関西支部賞
     リン原子および硫黄原子の元素特性を利用した新規反応の開発
  • 2009年 プロセス化学会 2009JSPC優秀賞
     メチレンアセタールの非常に緩和で高選択的な脱保護法の開発 
    受賞者: 藤岡弘道;瀬波賢人;久保大空;南辻裕;前川智弘
  • 2008年 有機合成化学協会 東海支部 平成20年度有機合成化学協会東海支部奨励賞
     白金族系触媒を用いた水素同位体標識化法の応用と芳香環水素化反応の開発 
    受賞者: 前川 智弘

共同研究・競争的資金等の研究課題

  • 硫黄化合物を用いる高活性なハロゲン化反応の開発とその応用
    文部科学省:科学研究費補助金(基盤研究(C))
    研究期間 : 2018年04月 -2022年03月 
    代表者 : 前川 智弘
  • 文部科学省:科学研究費補助金(基盤研究(C))
    研究期間 : 2014年 -2016年 
    代表者 : 前川 智弘
     
    ジオール類の保護基であるメチレンアセタールの新規変換反応について研究を行い、以下の成果を得た。 (1)メチレンアセタールに対してフェニルチオトリメチルシランとN-ブロモスクシンイミドを作用させることで新規開裂反応が進行し、対応するブロモホルメート体が得られることを見いだした。(2)ブロモホルメート体をNaOMeで処理することにより、対応するエポキシド体へと変換することに成功し、さらにメチレンアセタール体からの一段階での変換にも成功した。(3)アミノアルコール由来のメチレンアセタール体でも同様の反応が進行することを見いだした。
  • 文部科学省:科学研究費補助金(若手研究(B))
    研究期間 : 2012年 -2013年 
    代表者 : 前川 智弘
     
    ルイス酸存在下、MOMエーテルとトリメチルホスファイトから得られるO,P-アセタールを鍵中間体として、ジメチル基などの生物学的等価体として注目を集める4員環化合物であるオキセタン‐3‐オンならびに天然物中にみられる5員環化合物であるオキソラン-3-オンの効率的な合成法の開発に成功した。環構築後に残存するリン原子を活用して種々のアルデヒドとのHorner-Wadsworth-Emmons反応により、様々な置換基を有する多様な誘導体の簡便合成が可能である。また、出発原料をN,P-アセタールに代えることで、アゼチジン‐3‐オン、ピロリジン‐3‐オン誘導体を効率的に合成することにも成功した。さらに本法を応用し、抗腫瘍活性を有するpseudodeflectusinの短工程かつ高収率での合成を達成することができた。
  • ホスホニウム塩中間体を利用する有機合成化学:新規基盤反応の開発と天然物合成への応用
    武田科学振興財団:薬学系研究奨励
    研究期間 : 2011年 -2013年 
    代表者 : 前川 智弘
  • 日本学術振興会:科学研究費助成事業
    研究期間 : 2006年 -2007年 
    代表者 : 佐治木 弘尚; 前川 智弘; 門口 泰也
     
    水素の安定同位体である重水素(D)で標識された化合物は安定で長期保存が可能なため、生体内の薬物動態や化学反応における反応機構の解明、タンパク質や酵素などの高次構造解析に使用される利用価値の高い化合物である。しかし重水素標識化合物は高価であり、入手可能な標識体が限定されている。重水素導入法としては重水素(D2)ガスを用いた還元反応が多用される。例えば、不飽和結合の接触重水素化、脱ハロゲン化、ベンジルアルコールの還元やエポキシドのD2還元反応などは重水素標識化合物の有用な合成法である。その他にも、D2ガスは原子炉劣化D20の再生や、LSI(大規模集積圓路)の製造工程でも利用されておりその有用性は高い。しかしD2ガスは極めて高価である。これは、その製法がD20の電気分解やH2ガス中に微量(約150ppm)存在するD2ガスの極低温.下での液化分留法に頼っているため、エネルギーや反応の効率に起因する。従って工業スケールにも対応したより実用的なD2ガス発生法の開発は極めて重要である。 本研究課題は、我々がPd/Cを用いた官能基選択的な接触還元反応の開発研究の過程で、重水素化溶媒を反応溶媒としたところ反応基質に重水素が導入されることを見出した事から発展した。このPd/C触媒による重水素標識化法は、温和な中性条件下、重水素源としては最も安価なD20を用いる実用的手法である。平成18年度から19年度にかけて継続的に、Pd/C-D20-H2システムによるベンジル位選択的H-D交換反応の効率を向上し、より実用的な反応とするため、特に「反応時間の短縮及び基質適用性の拡大」を集中的に検討した。さらに、平成19年度は、これまでのH-D交換反応の検討過程で見出した、Pd/C触媒によるD20とH2間の、室温下における高効率的「H2-D2交換反応」、すなわち触媒反応による化学的D2ガス発生法の実用化を目指し、「反応条件の最適化」および、発生させたD2ガスを利用した「還元性官能基を有する化合物のone-pot接触重水素化反応」への適用を鋭意検討した。その結果重水素標識化合物の簡便合成法の確立に成功した。さらに、「官能基選択的one-pot接触重水素化法」、「反応容器内で発生させたD2ガスの採集法」及び「採集したD2ガスを用いた様々な基質の重水素標識法」も確立した。
  • 文部科学省:科学研究費補助金(若手研究(B))
    研究期間 : 2005年 -2006年 
    代表者 : 前川 智弘
     
    タンパク質や酵素等の高次構造解析や反応機構の解明等に用いられる重水素(D)標識化合物は小分子量のD標識シントンやH-D交換反応等により合成されるが、いずれの手法も手間がかかる、高価な試薬・特殊な反応条件を必要とするなどの問題点を有している。一方、当研究室ではこれまでにPd/C-D_2O-H_2の組み合わせによる簡便重水素化法の開発に成功し、一般性ある高効率的D標識体合成法として確立している。また、Pt/C存在下では芳香環上でのD化反応が優先的に進行することを見出し、さらにPd/C及びPt/C共存下では芳香環及びアルキル炭素上でのD化反応が同時に進行し1段階での多重D化反応が進行することを見出している。そこでより効率的なD化法並びにD化触媒の開発を目的として異なる触媒反応点を有するPdとPtを活性炭に同時に担持させた複合金属触媒の調製及び反応性の検討を行った。まず触媒を調製するにあたり、触媒の調製法による反応性の違いについて検討した。一般にPdの活性炭担持型触媒の調製法としては2価のPd金属の溶液中に活性炭を加えた後、還元剤で0価に還元する方法により調製する。そこで今回、より高活性な複合触媒の調製を目的として、還元剤に水素、ヒドラジン、ホルムアルデヒド、水素化ホウ素ナトリウムの4種を用いて触媒を調製したところ、水素化ホウ素ナトリウムを還元剤に用いて調製した触媒が最も高い活性を示し、芳香環、アルキル側鎖共に高効率的にD化を受けることが明らかとなった。また、本触媒はD化反応において相乗効果が発現することが明らかとなり、Pd/CまたはPt/Cを単独で用いた場合よりも高い重水素化率で反応が進行し、特に立体的に込み合った部位での重水素化が効率的に進行することを明らかとした。
  • Efficient and facile C-H/C-D exchange reaction of organic compounds using heterogeneous Pd/C.
    研究期間 : 2003年 -2006年
  • 日本学術振興会:科学研究費助成事業
    研究期間 : 2004年 -2005年 
    代表者 : 廣田 耕作; 佐治木 弘尚; 前川 智弘
     
    インターフェロン誘導活性を有する9-bennzyl-8-hydroxyadenine(1)の発見に基づいて、標記研究課題を達成するために以下の3項目の研究を実施したので、以下にその成果を要約する。 1.アデニン環2位の化学修飾による高活性インターフェロン誘導剤の合成:化合物(1)は経口吸収性が低く、経口薬として開発するには問題点を含んでいる。吸収性の向上を期待して2位のアルキル基末端にヘテロ原子を有する誘導体を合成した。その中で、-O(CH_2)_2OMe(2)および-SCH_2OMe(3)が置換した誘導体がこれまでに最も高い活性を示した化合物と同等のインターフェロン誘導活性を示した。 2.デアザアデニン誘導体の合成:上記と同様の観点から、化合物(1)に比較して薬物動態の点で優れた性質が期待される3-及び1-デアザアデニン誘導体をデザインした。4-アミノ-2,6-ジクロロピリジンを出発物質として、2種の9-bennzyl-2-butoxy-3-deazaadenine及び9-bennzyl-2-butoxy-1-deazaadenineを合成した。これらの化合物は対応するアデニン誘導体に比較して脂溶性が向上しており、経口吸収性の改善が期待される。現在、これらの化合物の8位へのヒドロキシル基の導入を検討中である。 3.トール様受容体7(TLR-7)の蛍光性リガンドの合成:8-ヒドロキシアデニン誘導体がインターフェロン誘導活性を示す機構としてTLR-7のアゴニスト作用によると考えられる。したがって、TLR-7の構造および機能解析のプローブ開発を目的として、アデニン環9位に蛍光性官能基を導入した誘導体の合成を行った。ナフチルメチル基の導入ではインターフェロン誘導活性を示したが蛍光の発現は極めて低かった。また、強い蛍光を示すアントラニルメチル基やチオフェン置換誘導体では溶解性や反応性に問題があり、現時点では目的とする化合物の合成には至っていない。
  • 日本学術振興会:科学研究費助成事業
    研究期間 : 2001年 -2002年 
    代表者 : 前川 智弘
     
    今回、申請者らは、水中での無機塩KBrの添加による低反応性、低溶解性の超原子価ヨウ素試薬PhIOの新規活性化法を利用したアルコール類の酸化反応の更なる展開を目的として研究を行った。まず、前年度、我々が見出したジオール類の酸化反応の拡張として異種分子間での酸化的エステル化反応を検討した。その結果、第1級アルコールの酸化反応の際にメタノールを共存させることで種々の第1級アルコール類から対応するメチルエステル体を収率良く得ることに成功した。今回、我々が見出した方法は一般性も高く、無水条件や過剰量の試薬を必要とした従来法に比べ、含水条件で行える簡便かつ収率の良いメチルエステル化反応である。さらに回収、再利用が可能なポリマー担持型超原子価ヨウ素試薬poly(diactoxyiodo)styrene(PDAIS)の利用を検討した結果、水中でのアルコール類の酸化反応と同様、本反応においても首尾良く反応が進行し、試薬のリサイクルも問題なく行えることが分かった。また、本活性化法を用いても困難であった電子吸引基を有する低活性なビアリールスルフィド類の酸化反応においてPhIOに比べ、より活性なphenyliodine diacetate (PIDA)を用いることでスルホンをほとんど副生することなく対応するスルホキシド類を収率良く与えることを見出した。また、PDAISを用いても首尾良く反応が進行し、種々のスルフィド類から対応するスルホキシド類を高収率で得ることに成功した。

その他

  • 2015年04月 - 2015年04月  金属触媒を用いる直接的なカップリング反応を利用した新規カルコン合成法の開発 
    近畿大学学内研究助成金 奨励研究助成金 SR06 研究内容: 金属触媒によるHeck反応を利用したハロゲンを持たない芳香環とビニルケトンとの直接的カップリング反応によるカルコン合成法の確立を目指す。

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