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YAMASHITA Mitsuaki

    Department of Applied Biological Chemistry　Associate Professor
Last Updated :2024/04/25

Researcher Information

URL

Research funding number

  • 20433641

J-Global ID

Research Interests

  • 生物有機化学   天然物化学   有機金属   合成化学   不斉合成   有機化学   

Research Areas

  • Life sciences / Bioorganic chemistry
  • Life sciences / Pharmaceuticals - chemistry and drug development

Academic & Professional Experience

  • 2019/04 - Today  Kindai UniversityFaculty of AgricultureAssociate Professor
  • 2012/04 - 2019/03  Kindai UniversityFaculty of Agriculture講師
  • 2006/04 - 2012/03  Takasaki University of Health and WelfareFaculty of Pharmacy助教

Education

  • 2003/04 - 2006/03  京都大学大学院  薬学研究科博士後期課程  創薬科学専攻
  • 2001/04 - 2003/04  京都大学大学院  薬学研究科修士課程  創薬科学専攻
  • 1996/04 - 2001/03  Nagoya City University  Medicin  Medicin

Association Memberships

  • THE SOCIETY OF SYNTHETIC ORGANIC CHEMISTRY, JAPAN   THE CHEMICAL SOCIETY OF JAPAN   THE PHARMACEUTICAL SOCIETY OF JAPAN   

Published Papers

  • Mitsuaki Yamashita; Yuto Nakamori; Arisa Tsukamoto; Nagisa Furuno; Akira Iida
    Bioorganic & medicinal chemistry 90 117331 - 117331 2023/07 
    Based on previous studies, we synthesized a novel class of ortho- and para-naphthoquinones derivatives bearing a phenolic hydroxy or sulfonamide moiety and evaluated their in vitro antiproliferative and signal transducer and activator of transcription-3 (STAT3) phosphorylation inhibitory activities. The biological evaluations of these naphthoquinones revealed that ortho-naphthoquinones containing a phenolic hydroxyl group exhibited greater antiproliferative activity compared to compounds without a phenolic hydroxyl group. Among the synthesized para-naphthoquinones, 21, which has a condensed sulfonamide structure, showed substantially higher antiproliferative activity than that of the parent compound, and was also found to inhibit the phosphorylation of STAT3(Y705) in a dose-dependent manner. A docking simulation using AutoDock Vina suggested that 21 could directly bind to the hinge region of STAT3.
  • Fusako Kawai; Yoshitomo Furushima; Norihiro Mochizuki; Naoki Muraki; Mitsuaki Yamashita; Akira Iida; Rie Mamoto; Takehiko Tosha; Ryo Iizuka; Sakihito Kitajima
    AMB Express 12 (1) 134 - 134 2022/10 
    The enzymatic recycling of polyethylene terephthalate (PET) can be a promising approach to tackle the problem of plastic waste. The thermostability and activity of PET-hydrolyzing enzymes are still insufficient for practical application. Pretreatment of PET waste is needed for bio-recycling. Here, we analyzed the degradation of PET films, packages, and bottles using the newly engineered cutinase Cut190. Using gel permeation chromatography and high-performance liquid chromatography, the degradation of PET films by the Cut190 variant was shown to proceed via a repeating two-step hydrolysis process; initial endo-type scission of a surface polymer chain, followed by exo-type hydrolysis to produce mono/bis(2-hydroxyethyl) terephthalate and terephthalate from the ends of fragmented polymer molecules. Amorphous PET powders were degraded more than twofold higher than amorphous PET film with the same weight. Moreover, homogenization of post-consumer PET products, such as packages and bottles, increased their degradability, indicating the importance of surface area for the enzymatic hydrolysis of PET. In addition, it was required to maintain an alkaline pH to enable continuous enzymatic hydrolysis, by increasing the buffer concentration (HEPES, pH 9.0) depending on the level of the acidic products formed. The cationic surfactant dodecyltrimethylammonium chloride promoted PET degradation via adsorption on the PET surface and binding to the anionic surface of the Cut190 variant. The Cut190 variant also hydrolyzed polyethylene furanoate. Using the best performing Cut190 variant (L136F/Q138A/S226P/R228S/D250C-E296C/Q123H/N202H/K305del/L306del/N307del) and amorphous PET powders, more than 90 mM degradation products were obtained in 3 days and approximately 80 mM in 1 day.
  • Akane Senga; Nobutaka Numoto; Mitsuaki Yamashita; Akira Iida; Nobutoshi Ito; Fusako Kawai; Masayuki Oda
    Journal of biochemistry 169 (2) 207 - 213 2021/03 [Refereed]
     
    An enzyme, Cut190, from a thermophilic isolate, Saccharomonospora viridis AHK190 could depolymerize polyethylene terephthalate (PET). The catalytic activity and stability of Cut190 and its S226P/R228S mutant, Cut190*, are regulated by Ca2+ binding. We previously determined the crystal structures of the inactive mutant of Cut190*, Cut190*S176A, in complex with metal ions, Ca2+ and Zn2+, and substrates, monoethyl succinate and monoethyl adipate. In this study, we determined the crystal structures of another mutant of Cut190*, Cut190**, in which the three C-terminal residues of Cut190* are deleted, and the inactive mutant, Cut190**S176A, in complex with metal ions. In addition to the previously observed closed, open and engaged forms, we determined the ejecting form, which would allow the product to irreversibly dissociate, followed by proceeding to the next cycle of reaction. These multiple forms would be stable or sub-stable states of Cut190, regulated by Ca2+ binding, and would be closely correlated with the enzyme function. Upon the deletion of the C-terminal residues, we found that the thermal stability increased while retaining the activity. The increased stability could be applied for the protein engineering of Cut190 for PET depolymerization as it requires the reaction above the glass transition temperature of PET.
  • Mitsuaki Yamashita; Jun Sawano; Ryuji Umeda; Ayuka Tatsumi; Yuko Kumeda; Akira Iida
    Chemical & pharmaceutical bulletin 69 (7) 661 - 673 2021 [Refereed]
     
    In this study, based on our previous study, derivatives of naphtho[2,3-b]furan-4,9-diones were synthesized and their antimicrobial activities were evaluated. The screening of these naphthoquinones revealed that the fluorine-containing NQ008 compound exhibited potent and broad antimicrobial activities against Gram-positive bacteria including methicillin-resistant Staphylococcus aureus (MRSA), Gram-negative bacteria, and fungi. The results of the ratio of the minimum bactericidal concentration (MBC) to the minimum inhibitory concentrations (MICs) and time-kill assays suggest that the mode of action of NQ008 is bactericidal. Additionally, the results of a drug resistance study revealed that NQ008 exhibited potent antibacterial activity and may delay the development of bacteria resistance. Furthermore, NQ008 exhibited preliminary antiviral activity against the swine influenza virus and Feline calicivirus.
  • Teruyuki Tahara; Ami Watanabe; Maho Yutani; Yuko Yamano; Mami Sagara; Shizu Nagai; Keita Saito; Mitsuaki Yamashita; Makoto Ihara; Akira Iida
    Bioorganic & medicinal chemistry 28 (6) 115347 - 115347 2020/03 [Refereed]
     
    The extract of Tabebuia avellanedae has been used as a folk medicine, and the various biological activities of T. avellanedae have been extensively studied. However, few studies have reported which natural products play a role in their biological effects. In this study, we evaluated representative naphthoquinones isolated from T. avellanedae and found that furanonaphthoquinones were the key structures required to exhibit STAT3 phosphorylation inhibitory activities. Our SAR analysis indicated that removal of a hydroxyl group enhanced the STAT3 phosphorylation inhibitory activity. In addition, the combined results of a mobility shift assay, SH2 domain binding assay, and docking simulation by Autodock 4.2.6 suggested that (S)-5-hydroxy-2-(1-hydroxyethyl)naphtho[2,3-b]furan-4,9-dione (1) could directly bind to the hinge region of STAT3.
  • Mitsuaki Yamashita; Syuhei Hata; Jun Sawano; Ryuji Umeda; Akira Iida
    HETEROCYCLES PERGAMON-ELSEVIER SCIENCE LTD 100 (2) 225 - 240 0385-5414 2020/02 [Refereed]
     
    A concise and efficient synthesis method for the preparation of antiproliferative ortho-naphthoquinones is described. Notably, the synthesis of ortho-furanonaphthoquinone was achieved by utilizing a regioselective oxidative conjugate addition of dimethylamine and the Sonogashira coupling/cyclization reaction as the key steps. Additionally, an improved synthesis of hydroxy-P-lapachone was established and included a regioselective prenylation by directed ortho-lithiation. In vitro antiproliferative effects of the synthesized against a panel of 39 human cancer cell lines were evaluated and the results were directly compared to those previously obtained for 1.
  • Yamashita Mitsuaki; Hayakawa Shinya; Hata Shuhei; Murakami Honoka; Fukuda Youichi; Iida Akira
    HETEROCYCLES 97 (2) 960 - 967 0385-5414 2018/09 [Refereed]
  • Mitsuaki Yamashita; Teruyuki Tahara; Shinya Hayakawa; Hironobu Matsumoto; Shun-ichi Wada; Kiyoshi Tomioka; Akira Iida
    Bioorganic and Medicinal Chemistry Elsevier Ltd 26 (8) 1920 - 1928 1464-3391 2018/05 [Refereed]
     
    HDAC inhibitors enable histones to maintain a high degree of acetylation. The resulting looser state of chromatin DNA may increase the accessibility of DNA drug targets and consequently improve the efficiency of anticancer drugs targeting DNA, such as Topo II inhibitors. A novel class of nucleoside-SAHA derivatives has been designed and synthesized based on the synergistic antitumor effects of topoisomerase II and histone deacetylase inhibitors. Their inhibitory activities toward histone deacetylases and Topo II, and their cytotoxicities in cancer cell lines, were evaluated. Among the synthesized hybrid compounds, compound 16b showed the potent HDAC inhibitory activity at a low nanomolar level and exhibited antiproliferative activity toward cancer cell lines including MCF-7 (breast), HCT-116 (colon), and DU-145 (prostate) cancer cells at a low micromolar level. Moreover, compound 16a showed HDAC6-selectivity 20-fold over HDAC1.
  • Hironobu Matsumoto; Mitsuaki Yamashita; Teruyuki Tahara; Shinya Hayakawa; Shun-Ichi Wada; Kiyoshi Tomioka; Akira Iida
    BIOORGANIC & MEDICINAL CHEMISTRY PERGAMON-ELSEVIER SCIENCE LTD 25 (15) 4133 - 4144 0968-0896 2017/08 [Refereed]
     
    We developed novel nucleoside-based topoisomerase II selective inhibitors and showed that small structural units, such as catechols, are essential for DNA topoisomerase II inhibitory activity. Moreover, nucleoside analogues containing TBS and 1,3-dithian moieties had potent and selective DNA topoisomerase II inhibitory activities. In further experiments, compound 25b having a beta configuration of the thymine moiety showed relatively strong growth inhibitory activity against cancer cell lines, and was more potent against all cancer cell lines than compound 26b, which carries a thymine moiety in the alpha configuration. (C) 2017 Elsevier Ltd. All rights reserved.
  • Kazuko Iwamoto; Youichi Fukuda; Chisato Tokikura; Mayuko Noda; Ayami Yamamoto; Misato Yamamoto; Mitsuaki Yamashita; Nobuhiro Zaima; Akira Iida; Tatsuya Moriyama
    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS ACADEMIC PRESS INC ELSEVIER SCIENCE 478 (3) 1136 - 1140 0006-291X 2016/09 [Refereed]
     
    Estrogen deficiency-induced obesity has a high risk of visceral fat accumulation and body weight gain. It is also associated with many adverse health conditions. Taheebo extract from Tabebuia avellanedae has been recognized as playing several biological and pharmacological roles. Therefore, we investigated whether the intake of n-BuOH extract of Taheebo shows anti-obesity effect in ovariectomized (OVX) mice. After 16 weeks of feeding, the mice administrated with 0.5% n-BuOH extract of Taheebo showed significantly decreased body weight compared with that of the control mice, and the fat mass also showed a significant decrease. In 3T3-L1 cells, supplementation with n-BuOH extract of Taheebo significantly reduced the triglyceride ( TG) levels. Furthermore, bioassay-guided purification of the nBuOH extract based on the TG levels in 3T3-L1 cells led to the isolation of compound 2 ( 1-dehydroxy-3,4-dihydroaucubigenin). These results suggested that the anti obesity effect of Taheebo extract is due to its capability in preventing the accumulation of adipocyte in mice. Taheebo extract might be a promising functional food resources capable of protecting against OVX-induced obesity. (C) 2016 Elsevier Inc. All rights reserved.
  • Mitsuaki Yamashita; Yukari Nishizono; Seiya Himekawa; Akira Iida
    TETRAHEDRON PERGAMON-ELSEVIER SCIENCE LTD 72 (27-28) 4123 - 4131 0040-4020 2016/07 [Refereed]
     
    We developed facile one-pot methods for the transformation of 2-arylindoles to polyhydropyrido[1,2-a]indoles and tetracyclic quinazolinones. The copper-catalyzed oxidation of 2-arylindoles to C-acylimines followed by aza-Diels-Alder reactions or oxidative ring-expansion reactions afforded significant polycyclic heterocycles. (C) 2016 Elsevier Ltd. All rights reserved.
  • Katsumi Nishimura; Naoshi Fukuyama; Tomohisa Yasuhara; Mitsuaki Yamashita; Takaaki Sumiyoshi; Yasutomo Yamamoto; Ken-ichi Yamada; Kiyoshi Tomioka
    TETRAHEDRON PERGAMON-ELSEVIER SCIENCE LTD 71 (39) 7222 - 7226 0040-4020 2015/09 [Refereed]
     
    The chiral diether ligand-controlled asymmetric conjugate addition of organolithiums to nona-2,7-dienedioate and subsequent intramolecular conjugate addition of the enolate intermediate gave alltrans trisubstituted cyclohexanes with high ee and yields. Using this methodology, an efficient short asymmetric total synthesis of (+)-beta-lycorane was accomplished in 33% overall yield through five steps from the dienedioate. (C) 2015 Elsevier Ltd. All rights reserved.
  • Katsumi Nishimura; Naoshi Fukuyama; Mitsuaki Yamashita; Takaaki Sumiyoshi; Yasutomo Yamamoto; Ken-ichi Yamada; Kiyoshi Tomioka
    SYNTHESIS-STUTTGART GEORG THIEME VERLAG KG 47 (15) 2256 - 2264 0039-7881 2015/08 [Refereed][Invited]
     
    The chiral diether ligand controlled asymmetric conjugate addition of organolithiums to nona-2,7-dienedioates preferentially proceeds via the s-cis conformation with coordination of the carbonyl oxygen atom to the lithium to give a lithium E-enolate intermediate. Subsequent intramolecular conjugate addition of the enolate also proceeds via a cyclic transition state involving the lithium and the s-cis-enoate, resulting in trans,trans-trisubstituted cyclohexanes with high enantiomeric excesses and yields.
  • Mitsuaki Yamashita; Akira Iida
    TETRAHEDRON PERGAMON-ELSEVIER SCIENCE LTD 70 (35) 5746 - 5751 0040-4020 2014/09 [Refereed]
     
    In this study, we describe a one-pot method to obtain a variety of 2-arylbenzoxazinones and N-benzoyl anthranilic acid by using a copper catalyst and molecular oxygen as oxidants. This protocol involves tandem cyclization and oxidative processes of 2-alkynylanilines to afford significant motifs in synthetic and medicinal chemistry with moderate yields. We also demonstrated that combining the Sonogashira coupling and the developed method realized the synthesis of 2-arylbenzoxazinones derivatives from commercially available 2-iodoanilines and terminal acetylenes. (C) 2014 Elsevier Ltd. All rights reserved.
  • Mitsuaki Yamashita; Akira Iida
    TETRAHEDRON LETTERS PERGAMON-ELSEVIER SCIENCE LTD 55 (18) 2991 - 2993 0040-4039 2014/04 [Refereed]
     
    We developed an efficient method for the transformation of indoles by utilizing a copper catalyst and molecular oxygen as the oxidant. The transformation involves a tandem oxidative process of 2-arylindoles. Our reaction afforded a variety of N-benzoyl anthranilic acids and benzoxazinones. Our investigation revealed that the choice of solvent and additives is critical in these reactions. (C) 2014 Elsevier Ltd. All rights reserved.
  • Kazunori Ueda; Mitsuaki Yamashita; Koichi Sakaguchi; Harukuni Tokuda; Akira Iida
    CHEMICAL & PHARMACEUTICAL BULLETIN PHARMACEUTICAL SOC JAPAN 61 (6) 648 - 654 0009-2363 2013/06 [Refereed]
     
    A concise method for the synthesis of heterocycle-fused naphthoquinones such as naphtho[2,3-b]-furan-4,9-dione, 1H-benz[f]indole-4,9-dione, and naphtho[2,3-b]thiophene-4,9-dione was developed. This method employed Sonogashira coupling and tandem addition-elimination/intramolecular cyclization, and it enabled the preparation of versatile heterocycle-fused naphthoquinones from one substrate.
  • Copper-catalyzed tandem intramolecular cyclization/coupling reaction: solvent effect on reaction pathway
    M. Yamashita; T. Noro; A. Iida
    Tetrahedron Letters 54 (50) 6848 - 6851 2013 [Refereed]
  • Mitsuaki Yamashita; Kazunori Ueda; Koichi Sakaguchi; Harukuni Tokuda; Akira Iida
    CHEMICAL & PHARMACEUTICAL BULLETIN PHARMACEUTICAL SOC JAPAN 59 (10) 1289 - 1293 0009-2363 2011/10 [Refereed]
     
    In this paper, a concise one-pot method for the construction of benzo[f]indole-4,9-dione motifs is described. These transformations proceed via a sequential palladium- and copper-catalyzed coupling reaction of 1,4-naphthoquinones with terminal acetylenes, followed by a copper-catalyzed intramolecular cyclization reaction of the resulting coupling product.
  • Mitsuaki Yamashita; Kazunori Ueda; Koichi Sakaguchi; Akira Iida
    TETRAHEDRON LETTERS PERGAMON-ELSEVIER SCIENCE LTD 52 (36) 4665 - 4670 0040-4039 2011/09 [Refereed]
     
    A mild strategy for constructing indolequinone motifs is described on the basis of the Sonogashira reaction and a copper-catalyzed intramolecular cyclization cascade reaction. The first step involves the palladium- and copper-catalyzed reaction between halogenated naphthoquinone and terminal acetylene to generate a coupling product, which then reacts in a copper-catalyzed intramolecular cyclization with the nitrogen functional group adjacent to the carbon-carbon triple bond. (C) 2011 Elsevier Ltd. All rights reserved.
  • Tomoko Mineno; Haruyasu Hirayama; Kazuhide Nakahara; Mitsuaki Yamashita; Hisao Kansui; Hiroshi Moriwaki
    Tetrahedron Letters 51 (46) 6045 - 6048 0040-4039 2010/11 [Refereed]
     
    The indium-promoted chemoselective deprotection of 2,2,2-trichloroethyl esters containing a benzylic methylene was successfully achieved by employing deuterated solvents. © 2010 Elsevier Ltd. All rights reserved.
  • Mitsuaki Yamashita; Masafumi Kaneko; Harukuni Tokuda; Katsumi Nishimura; Yuko Kumeda; Akira Iida
    BIOORGANIC & MEDICINAL CHEMISTRY PERGAMON-ELSEVIER SCIENCE LTD 17 (17) 6286 - 6291 0968-0896 2009/09 [Refereed]
     
    A series of naphthoquinones based on the naphtho[2,3-b]furan-4,9-dione skeleton such as (-)-5-hydroxy- 2-(1'-hydoxyethyl)naphtho[2,3-b]furan-4,9-dione (1) and its positional isomer, (-)-8-hydroxy- 2-(1'-hydoxyethyl)naphtho[2,3-b]furan-4,9-dione (2), which are secondary metabolites found in the inner bark of Tabebuia avellanedae, were stereoselectively synthesized and their biological activities were evaluated in conjunction with those of their corresponding enantiomers. Compound 1 exhibited potent antiproliferative effect against several human tumor cell lines, but its effect against some human normal cell lines was much lower than that of mitomycin. On the other hand, its enantiomer (R)-1 was less active toward the above tumor cell lines than 1. The antiproliferative effect of 2 against all tumor cell lines was significantly reduced. These results indicated the presence of the phenolic hydroxy group at C-5 is of great important for increasing antiproliferative effect. In addition, 1 also showed higher cancer chemopreventive activity than 2, while there were no significant differences between 1 and 2 in antimicrobial activity. Both compounds displayed modest antifungal and antibacterial activity (Gram-positive bacteria), whereas they were inactive against Gram-negative bacteria. (C) 2009 Elsevier Ltd. All rights reserved.
  • Harukuni Tokuda; Mitsuaki Yamashita; Masafumi Kaneko; Akira Iida
    CANCER RESEARCH AMER ASSOC CANCER RESEARCH 69 0008-5472 2009/05 [Refereed]
  • Ken-ichi Yamada; Mitsuaki Yamashita; Takaaki Sumiyoshi; Katsumi Nishimura; Kiyoshi Tomioka
    ORGANIC LETTERS AMER CHEMICAL SOC 11 (7) 1631 - 1633 1523-7060 2009/04 [Refereed]
  • Mitsuaki Yamashita; Masafumi Kaneko; Akira Iida; Harukuni Tokuda; Katsumi Nishimura
    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS PERGAMON-ELSEVIER SCIENCE LTD 17 (23) 6417 - 6420 0960-894X 2007/12 [Refereed]
     
    Stereoselective synthesis of 1, one of biologically active naphthoquinones from a Brazilian traditional medicine Tabebuia avellanedae, was achieved by utilizing Noyori reduction as a key step. Compound 1 displayed potent cytotoxicity against several human tumor cell lines, whereas it showed lower cytotoxicity against some human normal cell lines compared with that of mitomycin. On the other hand, its enantiomer was less active toward the tumor cell lines than 1. (c) 2007 Elsevier Ltd. All rights reserved.
  • Yamada Ken-ichi; Yamashita Mitsuaki; Nishimura Katsumi; Fukuyama Naoshi; Sumiyoshi Takaaki; Tomioka Kiyoshi
    Symposium on the Chemistry of Natural Products, symposium papers Symposium on the chemistry of natural products (49) 211 - 216 2007/08 
    We have been involved in development of asymmetric reactions using diether 2 as a chiral chelating ligand and have succeeded in asymmetric addition of organolithium reagents to α,β-unsaturated carboxylates (Scheme 1). The addition of organolithium reagent to α,β-unsaturated carboxylate gives lithium enolate intermediate, whose intermolecular trapping with another α,β-unsaturated carboxylate moiety would produce highly functionalized chiral cyclohexane building blocks, such as 4 (Scheme 2). We planned asymmetric synthesis of Amaryllidaceae alkaloids, lycorine (1) and related compounds using 4 as a key intermediate. The investigation of the key tandem asymmetric conjugate addition-cyclization reaction using chiral ligand 2 revealed that the bulky ortho-substituent, TMS group of aryllithium 6b using important to achieve the first addition step in high enantioselectivity (Scheme 3). Besides, the ethylenedioxy group of α,β-unsaturated carboxylate 3 improves diastereoselectivity in the cyclization step probably because the replacement of H with O makes 1,3-diaxial interaction more unfavorable in the transition state that gives trans-cis isomers 8 (Figure 2). With enantiomerically enriched cyclohexane 9 in hand, we started the asymmetric synthesis of lycorines (Scheme 4). Treatment of 9 with ethanolic HCl gave carboxylic acid 10, whose Curtius rearrangement gave carbamate 11 in good yield. Formation of the tetracyclic core was achieved via lactam formation and Bishler-Napieralski reaction to give ketone 14. Formal synthesis of 1-deoxylycorine was accomplished via double bond formation by IBX oxidation of silyl enolate and reduction of the resulting enone 15. Introduction of 2-hydroxy functionality to ketone 14 was achieved stereoselectively by Magnus' chemistry (Scheme5). Formation of double bond followed by reduction gave 2-epi-lycorine diacetate (23) after acetylation of the resulting 2-epi-lycorine (22).
  • M Yamashita; K Yamada; K Tomioka
    ADVANCED SYNTHESIS & CATALYSIS WILEY-V C H VERLAG GMBH 347 (11-13) 1649 - 1652 1615-4150 2005/10 [Refereed]
     
    Catalytic asymmetric alkynylation of aldehydes with terminal alkynes was catalyzed by zinc triflate and (1R,2R)-2-(dimethylamino)-1,2-diphenylethanol in toluene to give the corresponding, alcohols with high enantiomeric excess up to 98% in good yields.
  • M Yamashita; K Yamada; K Tomioka
    ORGANIC LETTERS AMER CHEMICAL SOC 7 (12) 2369 - 2371 1523-7060 2005/06 [Refereed]
     
    The asymmetric reaction of nitroolefins with arylalkynes was mediated by dimethylzinc (or diethylzinc) and (1R,2R)-2-(dimethylamino)-1,2-diphenylethanol in toluene to provide the corresponding conjugate alkynylation products with high enantiomeric excess of up to 99% in good yields. The presence of 0.03 equiv of galvinoxyl improved the reaction yield.
  • M Yamashita; KI Yamada; K Tomioka
    TETRAHEDRON PERGAMON-ELSEVIER SCIENCE LTD 60 (19) 4237 - 4242 0040-4020 2004/05 [Refereed]
     
    Asymmetric conjugate addition of 2-trityloxymethylpheyllithium to a nitroalkene was mediated by a chiral ligand to give the key intermediate for dopamine D1 full agonist dihydrexidine 1. The shortcut of both Curtius rearrangement and Pictet-Spengler type cyclization, which were the drawback of the previously reported synthesis involving asymmetric conjugate addition of phenyllithium to an enoate, was realized by the newly developed asymmetric reaction. Short and efficient synthetic way gave optically pure dihydrexidine in 45% overall yield via eight steps. Improved synthesis of the best chiral ligand 13 was realized under the Buchwald conditions. (C) 2004 Elsevier Ltd. All rights reserved.
  • T Yasuhara; E Osafune; K Nishimura; M Yamashita; K Yamada; O Muraoka; K Tomioka
    TETRAHEDRON LETTERS PERGAMON-ELSEVIER SCIENCE LTD 45 (15) 3043 - 3045 0040-4039 2004/04 
    (+/-)-gamma-Lycorane 3 was synthesized in 52% overall yield via seven steps from 5 by employing the highly stereoselective nitro-Michael cyclization of 5 to 9 and diastereoselective conjugate addition of aryllithium to a nitroolefin 10 as two key steps. (C) 2004 Elsevier Ltd. All rights reserved.
  • M Yamashita; KI Yamada; K Tomioka
    JOURNAL OF THE AMERICAN CHEMICAL SOCIETY AMER CHEMICAL SOC 126 (7) 1954 - 1955 0002-7863 2004/02 [Refereed]
  • T Yasuhara; K Nishimura; M Yamashita; N Fukuyama; K Yamada; O Muraoka; K Tomioka
    ORGANIC LETTERS AMER CHEMICAL SOC 5 (7) 1123 - 1126 1523-7060 2003/04 [Refereed]
     
    [GRAPHIC] An omega-nitro-alpha,beta,psi,omega-unsaturated ester underwent a chemoselective conjugate addition of a nitroolefin moiety with aryllithium to produce a psi-aryl-omega-nitro-alpha,beta-unsaturated ester, which was then stereoselectively cyclized by intramolecular nitro-Michael reaction giving a functionalized cyclohexane applicable to the total synthesis of (+/-)-alpha- and beta-lycoranes.
  • Y Asano; M Yamashita; K Nagai; M Kuriyama; K Yamada; K Tomioka
    TETRAHEDRON LETTERS PERGAMON-ELSEVIER SCIENCE LTD 42 (48) 8493 - 8495 0040-4039 2001/11 [Refereed]
     
    The first asymmetric synthesis of benzophenanthridine dopamine D1 full agonist, dihydrexidine, was accomplished employing three key processes, external chiral ligand-cont rolled conjugate addition of phenyllithium, Curtius conversion of a carboxylic group to an amino group, and finally Pictet-Spengler type cyclization completing skeleton construction. (C) 2001 Elsevier Science Ltd. All rights reserved.
  • K IKAI; A IIDA; M YAMASHITA
    SYNTHESIS-STUTTGART GEORG THIEME VERLAG (8) 595 - 597 0039-7881 1989/08 [Refereed]

Books etc

  • テルペン利用の新展開
    山下光明 (Joint work第5章 テルペン類の合成について)シーエムシー出版 2016/08

Conference Activities & Talks

  • Copper-mediated Oxidative Tandem Reactions: One-pot synthesis of Polyhydropyrido[1,2-a]indoles and Tetracyclic Quinazolinones from 2-Arylindoles  [Not invited]
    YAMASHITA Mitsuaki
    18th TETRAHEDRON SYMPOSIUM Asia Edition  2017/07
  • 銅触媒による酸化的タンデム反応の開発： pyrido[1,2-a]indolesとtetracyclic quinazolinonesの２－アリールインドールからのワンポット合成  [Not invited]
    山下光明
    日本薬学会第137年会（仙台）  2017/03
  • ＤＮＡトポイソメラーゼⅡ型阻害剤とヒストン脱アセチル化酵素阻害剤とのハイブリッド化合物の合成と評価  [Not invited]
    山下光明
    日本薬学会第136年会（横浜）  2016/03
  • DNA トポイソメラーゼⅡ型阻害剤とトリコスタチン類縁体とのハイブリッド化合物の合成と評価  [Not invited]
    山下光明
    第65 回 日本薬学会近畿支部総会・大会（大阪）  2015/10
  • 銅触媒と分子状酸素を用いた２－アリールインドールの酸化的タンデム反応の開発  [Not invited]
    山下光明
    日本薬学会第135年会（神戸）  2015/03
  • 銅触媒を用いたタンデム型３位置換インドール合成：非プロトン性極性溶媒の効果  [Not invited]
    山下光明
    日本薬学会第134年会（熊本）  2014/03
  • 複素環縮合ナフトキノン類の効率的合成法の開発  [Not invited]
    山下光明
    第42回 複素環化学討論会（京都）  2012/10
  • ヘテロ環縮合ナフトキノン類縁体の合成と抗がん活性  [Not invited]
    山下光明
    日本薬学会第130年会（岡山）  2010/03
  • ブラジル原産Tabebuia avellanedae由来活性成分の合成研究および生物活性  [Not invited]
    山下光明
    第27回 メディシナルケミストリーシンポジウム（大阪）  2008/11
  • ブラジル原産Tabebuia avellanedae由来の活性成分の合成研究  [Not invited]
    山下光明
    日本薬学会第127年会（富山）  2007/03

MISC

Industrial Property Rights

Research Grants & Projects

  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research
    Date (from‐to) : 2012 -2013 
    Author : YAMASHITA Mitsuaki
     
    A concise method for the synthesis of heterocycle-fused naphthoquinones such as 1H-benz[f]indole-4,9-dione was developed. This method employed Sonogashira coupling and tandem addition-elimination/intramolecular cyclization, and it enabled the preparation of versatile heterocycle-fused naphthoquinones from one substrate. However, introduction of C1 unit at 3-position was failed. Alternatively, we developed direct methods for the synthesis of 3-substituted indoles from o-alkynylanilines by utilizing a copper-catalyzed tandem intramolecular cyclization/coupling reaction. Moreover, we developed an efficient method for the transformation of indoles by utilizing a copper catalyst and molecular oxygen as the oxidant. The transformation involves a tandem oxidative process of 2-arylindoles. Our reaction afforded a variety of N-benzoyl anthranilic acids and benzoxazinones.
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research
    Date (from‐to) : 2011 -2012 
    Author : HANAOKA Hirofumi; YAMASHITA Mitsuaki
     
    We planned to develop a novel chelating agent suitable for the prelabeling to establish a generic method for preparation radiolabeled antibodies. CHX-DTPA was selected as a chelate group, and then CHX-DTPA-Bn-Gly, which conjugated Gly via benzene ring attached to backbone carbon, was designed and synthesized. The chelating agent could be radiolabeled with indium-111 at low concentration, and it showed rapid urinary excretion. These results indicated that CHX-DTPA-Bn-Gly is a promising mother compound of the novel chelating agent.
  • Ministry of Education, Culture, Sports, Science and Technology：Grants-in-Aid for Scientific Research(若手研究(B))
    Date (from‐to) : 2007 -2008 
    Author : Mitsuaki YAMASHITA
     
    本研究では未開拓分野である末端アセチレンの触媒的不斉共役付加反応及びその反応を端緒とした直接的かつ効率的な多置換ピペリジン骨格構築法の開発を目指した。有機リチウム試薬は有機合成化学では汎用される試薬であり、多種多様なものが存在する。その中でも、リチウムアセチリド種は他の有機リチウム試薬に比して反応性が低い。本研究では、その特性を活かした立体選択的な反応の開発を行った。

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