Researcher Database

Keiji Tanino
Faculty of Science Chemistry Organic and Biological Chemistry
Professor

Researcher Profile and Settings

Affiliation

  • Faculty of Science Chemistry Organic and Biological Chemistry

Job Title

  • Professor

URL

J-Global ID

Research Interests

  • 合成化学   全合成   反応開発   有機合成   

Research Areas

  • Nanotechnology/Materials / Synthetic organic chemistry
  • Life sciences / Bioorganic chemistry
  • Nanotechnology/Materials / Structural/physical organic chemistry

Academic & Professional Experience

  • 2006/04 - Today Hokkaido University Faculty of Science
  • 1999/08 - 2006/03 北海道大学大学院理学研究科 助教授
  • 1998/11 - 1999/07 北海道大学大学院理学研究科 助手
  • 1989/06 - 1998/10 Tokyo Institute of Technology School of Science

Education

  • 1987/04 - 1989/05  Tokyo Institute of Technology  Graduate School of Science and Engineering  Department of Chemistry
  • 1985/04 - 1987/03  Tokyo Institute of Technology  Graduate School of Science and Engineering  Department of Chemistry
  • 1982/04 - 1985/03  Tokyo Institute of Technology  School of Science  Dept. of Chemistry
  • 1981/04 - 1982/03  Tokyo Institute of Technology

Research Activities

Published Papers

  • Atsushi Nakayama, Akira Otani, Tsubasa Inokuma, Daisuke Tsuji, Haruka Mukaiyama, Akira Nakayama, Kohji Itoh, Akira Otaka, Keiji Tanino, Kosuke Namba
    Communications Chemistry 2020/12 [Refereed][Not invited]
  • Takahiro Suzuki, Takamune Yanagisawa, Keiji Tanino
    Heterocycles 99 (2) 848 - 855 2019/06 [Refereed][Not invited]
  • Rui Kamada, Nozomi Kimura, Fumihiko Yoshimura, Keiji Tanino, Kazuyasu Sakaguchi
    PLOS ONE 14 (2) e0212682  2019/02 [Refereed][Not invited]
  • Fumihiko Yoshimura, Taku Okada, Keiji Tanino
    Organic Letters 21 (2) 559 - 562 2019/01 [Refereed][Not invited]
  • Fumihiko Yoshimura, Taiki Abe, Yuichi Ishioka, Keiji Tanino
    The Journal of Antibiotics 72 (6) 384 - 388 2019/01 [Refereed][Not invited]
  • Hideomi Yamaga, Keiji Tanino
    Synlett 30 (2) 230 - 234 2018/12 [Refereed][Not invited]
  • Fumihiko Yoshimura, Ryusei Itoh, Makoto Torizuka, Genki Mori, Keiji Tanino
    Angewandte Chemie International Edition Wiley 57 (52) 17161 - 17167 2018/12 [Refereed][Not invited]
  • Takahiro Suzuki, Soichiro Watanabe, Muhammet Uyanik, Kazuaki Ishihara, Susumu Kobayashi, Keiji Tanino
    Organic Letters American Chemical Society ({ACS}) 20 (13) 3919 - 3922 2018/07 [Refereed][Not invited]
  • Rui Kamada, Fuki Kudoh, Fumihiko Yoshimura, Keiji Tanino, Kazuyasu Sakaguchi
    JOURNAL OF BIOCHEMISTRY 162 (4) 303 - 308 0021-924X 2017/10 [Refereed][Not invited]
     
    Protein phosphatase Magnesium-dependent 1, Delta (PPM1D) is a wild-type p53-inducible Ser/Thr phosphatase that acts as a negative regulator of the p53 tumor suppressor. Gene amplification and overexpression of PPM1D have been reported in various cancers including leukemia and neuroblastoma. Therefore, PPM1D is a promising target in cancer therapy. It has been reported that PPM1D knockout mice exhibit neutrophilia in blood and show a defective immune response. Here, we found that inhibition of PPM1D induced neutrophil differentiation of human promyelocytic leukemia cell line HL-60. The combination of a PPM1D inhibitor and all-trans retinoic acid significantly increased their differentiation efficiency. The PPM1D inhibitor also induced G1 arrest in HL-60 cells. Our results suggest that PPM1D may be a potential therapeutic target for blood cell diseases including leukemia.
  • Fumihiko Yoshimura, Hiroki Saito, Taiki Abe, Keiji Tanino
    SYNLETT 28 (14) 1816 - 1820 0936-5214 2017/09 [Refereed][Not invited]
     
    Upon treatment with triisopropylsilyl trifluoromethanesulfonate and 2,2,6,6-tetramethylpiperidine, alkanenitriles undergo direct addition to aldehydes under mild non-basic neutral conditions to provide triisopropylsilyl ethers of beta-hydroxy nitriles in good yield. The reaction proceeds through generation of an N-silyl ketene imine intermediate in situ from the alkanenitrile followed by nucleophilic addition of the intermediate to the aldehyde.
  • Daisuke Domon, Masaru Iwakura, Keiji Tanino
    TETRAHEDRON LETTERS 58 (20) 1957 - 1960 0040-4039 2017/05 [Refereed][Not invited]
     
    A new method for achieving the decyanation of disubstituted malononitrile derivatives without using reducing agents has been developed. Treatment of a six-membered malononitrile derivative with NaHMDS followed by methanol afforded the corresponding acetonitrile derivative in high yield. The present method was applicable to the decyanation reactions of a variety of malononitriles including four and five-membered compounds as well as acyclic ones. (C) 2017 Elsevier Ltd. All rights reserved.
  • Masahiko Kinebuchi, Ryohei Uematsu, Keiji Tanino
    TETRAHEDRON LETTERS 58 (14) 1382 - 1386 0040-4039 2017/04 [Refereed][Not invited]
     
    A new method for constructing the polycyclic skeleton of psiguadial B (1), a meroterpenoid isolated from an evergreen shrub of Myrtaceae, was developed. The terpenoid substructure of 1 was constructed on the basis of a cascade double cyclization reaction of an alkyne dicobalt complex, which afforded the bicyclo [4.3.1]decane derivative having a benzyl group with the correct configuration. The substituted aromatic ring was introduced to the bridgehead position of the intermediate, and bromination under radical conditions followed by intramolecular cyclization reaction resulted in formation of the benzopyran moiety in a stereoselective manner. (C) 2017 Elsevier Ltd. All rights reserved.
  • Masaru Iwakura, Hiroshi Tokura, Keiji Tanino
    TETRAHEDRON LETTERS 58 (12) 1223 - 1226 0040-4039 2017/03 [Refereed][Not invited]
     
    A novel method for constructing a 7-oxabicyclo[2.2.1]heptane skeleton was developed. The substrates, namely cis-3,4-epoxy-1-cyclohexanol derivatives, were prepared from the corresponding 3-cyclohexen-1-ol derivatives via a stereoselective epoxidation reaction using a vanadium catalyst. Upon heating with lithium iodide in propionitrile, the cis-epoxy alcohol was transformed into the 7-oxabicyclo [2.2.1]heptane derivative in high yield. The reaction proceeds through formation of a lithium alkoxide bearing an iodohydrin moiety, followed by an intramolecular S(N)2 reaction. (C) 2017 Elsevier Ltd. All rights reserved.
  • Takahiro Suzuki, Soichiro Watanabe, Susumu Kobayashi, Keiji Tanino
    ORGANIC LETTERS 19 (4) 922 - 925 1523-7060 2017/02 [Refereed][Not invited]
     
    (+)-Iso-A82775C is a proposed biosynthetic precursor of the chloropupukeananin family and an important intermediate for related natural products. The first enantioselective total synthesis of (+)-iso-A82775C (18 steps, 2.2% overall yield) toward the eventual biomimetic total synthesis of chloropupukeananin is described. The key steps are (1) the enantioselective Diels Alder reaction of 4-bromo-3-hydroxy-2-pyrone with methyl 2-chloroacrylate using cinchonine as an organocatalyst and (2) the anti-selective Cu-mediated S(N)2' reaction to afford the axially chiral vinylallene moiety.
  • Kosuke Namba, Kohei Takeuchi, Yukari Kaihara, Keiji Tanino
    Yuki Gosei Kagaku Kyokaishi/Journal of Synthetic Organic Chemistry 75 (11) 1094 - 1101 0037-9980 2017 [Refereed][Not invited]
     
    Palau-amine has received a great deal of attention in the past two decades as an attractive synthetic target by virtue of its intriguing molecular architecture and significant immunosuppressive activity. Here, we report the total synthesis of Palau-amine characterized by the Hg(OTf)2- catalyzed construction of tetra-substituted carbon center at the C16 position and the construction of an ABDE tetracyclic ring core including a trans-bicylo[3.3.0]octane skeleton at a middle stage of total synthesis. The ABDE tetracyclic ring core is constructed by a cascade reaction of a cleavage of the N-N bond, including simultaneous formation of imine, the addition of amide anion to the resulting imine (D-ring formation), and the condensation of pyrrole with methyl ester (B-ring formation) in a single step. The present synthetic route has the potential to help elucidate a pharmacophore as well as the mechanistic details of immunosuppressive activity Palau-amine has received a great deal of attention in the past two decades as an attractive synthetic target by virtue of its intriguing molecular architecture and significant immunosuppressive activity. Here, we report the total synthesis of Palau-amine characterized by the Hg(OTf)2-catalyzed construction of tetra-substituted carbon center at the C16 position and the construction of an ABDE tetracyclic ring core including a trans-bicylo[3.3.0]octane skeleton at a middle stage of total synthesis. The ABDE tetracyclic ring core is constructed by a cascade reaction of a cleavage of the N-N bond, including simultaneous formation of imine, the addition of amide anion to the resulting imine (D-ring formation), and the condensation of pyrrole with methyl ester (B-ring formation) in a single step. The present synthetic route has the potential to help elucidate a pharmacophore as well as the mechanistic details of immunosuppressive activity.
  • Jun-Ichi Sawada, Ayumi Osawa, Tomoki Takeuchi, Masato Kaneda, Shinya Oishi, Nobutaka Fujii, Akira Asai, Keiji Tanino, Kosuke Namba
    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS 26 (23) 5765 - 5769 0960-894X 2016/12 [Refereed][Not invited]
     
    1,3a, 6a-Triazapentalene is a compact fluorescent chromophore. In this study, triazapentalene was used to modify a series of biphenyl-type inhibitors of kinesin spindle protein (KSP) to develop fluorescent probes for the intracellular visualization of this protein. Microscopic studies demonstrated that these novel triazapentalene-labeled compounds exhibited inhibitory activity towards KSP in cultured cells and provided important information concerning the intracellular distribution. (C) 2016 Elsevier Ltd. All rights reserved.
  • Kohei Takeuchi, Atsushi Nakayama, Keiji Tanino, Kosuke Namba
    SYNLETT 27 (18) 2591 - 2596 0936-5214 2016/11 [Not refereed][Not invited]
     
    An efficient method for converting isothioureas into guanidines was developed. The use of amine salts of bis(trifluoromethanesulfonyl)imide as a nitrogen source was found to induce an efficient conversion under weak acidic conditions at 50 degrees C. The conversion was applicable to the various amines and carbamate-protected thioureas, and various carbamate-protected cyclic guanidines were obtained in high yields. In particular, ammonium bis(trifluoromethanesulfonyl)imide salt is a useful N1 source with which to construct monoprotected cyclic guanidines.
  • Manabu Fujitani, Keiji Tanino
    TETRAHEDRON LETTERS 57 (43) 4838 - 4841 0040-4039 2016/10 [Refereed][Not invited]
     
    The stereoselective synthesis of the right-hand segment of enfumafungin, a potent antifungal agent isolated from a Hormonema sp., was achieved. The contiguous two quaternary carbon atoms at the angular positions of the trans-fused CD ring system was constructed through the stereoselective reduction of 4-cyano-3,4-dimethy1-2-cyclohexen-1-one and the Johnson-Claisen rearrangement. After elongation of the side chains, the D ring was formed via a stereoselective intramolecular conjugate addition reaction which was originally developed by our laboratory. (C) 2016 Elsevier Ltd. All rights reserved.
  • Rui Kamada, Fumi Tano, Fuki Kudoh, Nozomi Kimura, Yoshiro Chuman, Ayumi Osawa, Kosuke Namba, Keiji Tanino, Kazuyasu Sakaguchi
    PLOS ONE 11 (8) e0160625  1932-6203 2016/08 [Refereed][Not invited]
     
    Nuclear and cytoplasmic morphological changes provide important information about cell differentiation processes, cell functions, and signal responses. There is a strong desire to develop a rapid and simple method for visualizing cytoplasmic and nuclear morphology. Here, we developed a novel and rapid method for probing cellular morphological changes of live cell differentiation process by a fluorescent probe, TAP-4PH, a 1,3a, 6a-triazapentalene derivative. TAP-4PH showed high fluorescence in cytoplasmic area, and visualized cytoplasmic and nuclear morphological changes of live cells during differentiation. We demonstrated that TAP-4PH visualized dendritic axon and spine formation in neuronal differentiation, and nuclear structural changes during neutrophilic differentiation. We also showed that the utility of TAP-4PH for visualization of cytoplasmic and nuclear morphologies of various type of live cells. Our visualizing method has no toxicity and no influence on the cellular differentiation and function. The cell morphology can be rapidly observed after addition of TAP-4PH and can continue to be observed in the presence of TAP-4PH in cell culture medium. Moreover, TAP-4PH can be easily removed after observation by washing for subsequent biological assay. Taken together, these results demonstrate that our visualization method is a powerful tool to probe differentiation processes before subsequent biological assay in live cells.
  • Atsushi Nakayama, Satoshi Nishio, Akira Otani, Akane Mera, Ayumi Osawa, Keiji Tanino, Kosuke Namba
    CHEMICAL & PHARMACEUTICAL BULLETIN 64 (7) 830 - 837 0009-2363 2016/07 [Refereed][Not invited]
     
    Various 2,4-disubstituted-1,3a,6a-triazapentalenes possessing methyl and phenyl groups at the C4-position were synthesized. Fluorescence observation of the synthetic 4-methyl- and 4-phenyl-1,3a,6a-triazapentalenes revealed that the introduction of a substituent at the C4-position allowed a long-wavelength shift of the fluorescence maximum. Furthermore, the phenyl group at the C4-position was found to induce a substantial increase in the extinction coefficient value.
  • Fumihiko Yoshimura, Taiki Abe, Keiji Tanino
    ORGANIC LETTERS 18 (7) 1630 - 1633 1523-7060 2016/04 [Refereed][Not invited]
     
    The previously unexplored reactivity of N-silyl ketene imines in organic synthesis is reported. Benzyl nitriles containing an alkenyl or aryl group at the ortho position were smoothly converted into aryl amines in good yields under two sets of mild silylation conditions: (1) nonbasic conditions using TMSNTf2-iPr(2)NEt or (2) basic anionic conditions using lithium diisopropylamide-triisopropylsilyl chloride (LDA-TIPSCl). The reaction probably proceeds via in situ generation of an N-silyl ketene imine followed by 6 pi-electrocyclization and aromatization.
  • Atsushi Nakayama, Satoshi Nishio, Akira Otani, Akane Mera, Ayumi Osawa, Keiji Tanino, Kosuke Namba
    Chemical and Pharmaceutical Bulletin 64 (7) 830 - 837 1347-5223 2016 [Refereed][Not invited]
     
    Various 2,4-disubstituted-1,3a,6a-triazapentalenes possessing methyl and phenyl groups at the C4-position were synthesized. Fluorescence observation of the synthetic 4-methyl- and 4-phenyl-1,3a,6a-triazapentalenes revealed that the introduction of a substituent at the C4-position allowed a long-wavelength shift of the fluorescence maximum. Furthermore, the phenyl group at the C4-position was found to induce a substantial increase in the extinction coefficient value.
  • Kosuke Namba, Kohei Takeuchi, Yukari Kaihara, Masataka Oda, Akira Nakayama, Atsushi Nakayama, Masahiro Yoshida, Keiji Tanino
    NATURE COMMUNICATIONS 6 8731  2041-1723 2015/11 [Refereed][Not invited]
     
    Palau'amine has received a great deal of attention in the past two decades as an attractive synthetic target by virtue of its intriguing molecular architecture and significant immunosuppressive activity. Here we report the total synthesis of palau'amine characterized by the construction of an ABDE tetracyclic ring core including a trans-bicylo[3.3.0] octane skeleton at a middle stage of total synthesis. The ABDE tetracyclic ring core is constructed by a cascade reaction of a cleavage of the N-N bond, including simultaneous formation of imine, the addition of amide anion to the resulting imine (D-ring formation) and the condensation of pyrrole with methyl ester (B-ring formation) in a single step. The synthetic palau'amine is confirmed to exhibit excellent immunosuppressive activity. The present synthetic route has the potential to help elucidate a pharmacophore as well as the mechanistic details of immunosuppressive activity.
  • Sari Ogasawara, Yuhei Kiyota, Yoshiro Chuman, Ayano Kowata, Fumihiko Yoshimura, Keiji Tanino, Rui Kamada, Kazuyasu Sakaguchi
    BIOORGANIC & MEDICINAL CHEMISTRY 23 (19) 6246 - 6249 0968-0896 2015/10 [Refereed][Not invited]
     
    Protein phosphatase magnesium-dependent 1 delta (PPM1D, Wip1) is a p53 inducible serine/threonine phosphatase. PPM1D is a promising target protein in cancer therapy since overexpression, missense mutations, truncating mutations, and gene amplification of PPM1D are reported in many tumors, including breast cancer and neuroblastoma. Herein, we report that a specific inhibitor, SL-176 that can be readily synthesized in 10 steps, significantly inhibits proliferation of a breast cancer cell line overexpressing PPM1D and induces G2/M arrest and apoptosis. SL-176 decreases PPM1D enzyme activity potently and specifically in vitro. These results demonstrate that SL-176 could be a useful lead compound in the development of effective anti-cancer agents. (C) 2015 Elsevier Ltd. All rights reserved.
  • Miki Shibata, Ryuichi Fuchigami, Ryota Kotaka, Kosuke Namba, Keiji Tanino
    TETRAHEDRON 71 (26-27) 4495 - 4499 0040-4020 2015/07 [Refereed][Not invited]
     
    An acid-catalyzed [4+3] cycloaddition reaction of N-nosyl pyrroles with 2-(tert-butyldimethylsilyloxy) acrolein has been developed. The reaction of 2-(silyloxy)acrolein with N-nosyl pyrrole was catalyzed by Tf2NH, and a regio- and stereoselective reaction with 2-substituted N-nosyl pyrroles leading to tropinone derivatives possessing tetra-substituted carbon centers was also achieved. High regioselectivities were obtained by using Cu(OTf)(2) or Sc(OTf)(3) as a catalyst in nitromethane, and the reaction was applicable to various 2-substituted N-nosyl pyrroles in good yields and with high regioselectivities. (C) 2015 Elsevier Ltd. All rights reserved.
  • Kosuke Namba, Ayumi Osawa, Akira Nakayama, Akane Mera, Fumi Tano, Yoshiro Chuman, Eri Sakuda, Tetsuya Taketsugu, Kazuyasu Sakaguchi, Noboru Kitamura, Keiji Tanino
    CHEMICAL SCIENCE 6 (2) 1083 - 1093 2041-6520 2015 [Refereed][Not invited]
     
    To expand the originally developed fluorescent 1,3a, 6a-triazapentalenes as fluorescent labelling reagents, the fluorescence wavelength of the 1,3a, 6a-triazapentalenes was extended to the red color region. Based on the noteworthy correlation of the fluorescence wavelength with the inductive effect of the 2-substituent, electron-deficient 2-(2-cyano-4-methoxycarbonylphenyl)-1,3a, 6a-triazapentalene and 2-(2,6-dicyano-4-methoxycarbonylphenyl)-1,3a, 6a-triazapentalene were synthesized. The former exhibited yellow fluorescence and the latter exhibited red fluorescence, and both compounds exhibited large Stokes shifts, and the 1,3a, 6a-triazapentalene system enabled the same fluorescent chromophore to cover the entire region of visible wavelengths. The potential applications of the 1,3a, 6a-triazapentalenes as fluorescent probes in the fields of the life sciences were investigated, and the 1,3a, 6a-triazapentalene system was clearly proven to be useful as a fluorescent reagent for live cell imaging. Quantum chemical calculations were performed to investigate the optical properties of the 1,3a, 6a-triazapentalenes. These calculations revealed that the excitation involves a significant charge-transfer from the 1,3a, 6a-triazapentalene skeleton to the 2-substituent. The calculated absorption and fluorescence wavelengths showed a good correlation with the experimental ones, and thus the system could enable the theoretical design of substituents with the desired optical properties.
  • Kentaro Sakurai, Keiji Tanino
    TETRAHEDRON LETTERS 56 (3) 496 - 499 0040-4039 2015/01 [Refereed][Not invited]
     
    Studies toward the asymmetric total synthesis of azadirachtin are explored. The ABC ring system was constructed through the stereoselective Diels-Alder reaction of an optically active vinyl allenylsilane derivative followed by an intramolecular aldol reaction. The highly hindered C8-C14 bond was formed by an intermolecular addition reaction of an aldehyde and the allylborane moiety in the B ring. Cyclization of the E ring moiety by the Pd-catalyzed Nazarov reaction afforded a compound having the highly functionalized ABCE ring system of azadirachtin. (C) 2014 Elsevier Ltd. All rights reserved.
  • Yuuki Kozakai, Rui Kamada, Yuhei Kiyota, Fumihiko Yoshimura, Keiji Tanino, Kazuyasu Sakaguchi
    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS 24 (24) 5593 - 5596 0960-894X 2014/12 [Refereed][Not invited]
     
    PPM1D is a p53-inducible Ser/Thr phosphatase. One of the main functions of PPM1D in normal cells is to act as a negative regulator of the p53 tumor suppressor by dephosphorylating p53 and several kinases. PPM1D is considered an oncoprotein owing to both its functions and the fact that gene amplification and overexpression of PPM1D are reported in several tumors. Recently, PPM1D mutations resulting in C-terminal truncated alterations were found in brainstem gliomas and colorectal cancers, and these mutations enhanced the activity of PPM1D. Therefore, C-terminal truncated PPM1D should be also considered as a potential candidate target of anticancer drugs. Here we showed that combination treatment with PPM1D-specific inhibitor SPI-001 and doxorubicin suppressed cell viability of HCT-116 cells overexpressing C-terminal truncated PPM1D through p53 activation compared with doxorubicin alone. Our results suggest that combination treatment with PPM1D inhibitor and doxorubicin may be a potential anti-cancer treatment in PPM1D-mutated cancer cells. (C) 2014 Elsevier Ltd. All rights reserved.
  • Fumihiko Yoshimura, Taiki Abe, Keiji Tanino
    SYNLETT 25 (13) 1863 - 1868 0936-5214 2014/08 [Refereed][Not invited]
     
    In the presence of triethylsilyl trifluoromethanesulfonate and triethylamine, aliphatic nitriles undergo addition reactions with aldonitrones under non-basic, mild conditions, providing O-triethylsilyl ethers of beta-N-hydroxyamino nitriles with high yield. The reaction appears to proceed through formation of an N-silyl ketene imine in situ followed by a Mannich-type reaction.
  • Kosuke Namba, Yoshihiro Shobo, Kazuki Fujimoto, Isamu Shoji, Masahiro Yoshida, Keiji Tanino
    EUROPEAN JOURNAL OF ORGANIC CHEMISTRY (24) 5196 - 5203 1434-193X 2014/08 [Refereed][Not invited]
     
    New halohydrazidation and hydrazidopalladation reactions were developed that use the synthon N-acyl-N-tosylhydrazine. The intramolecular bromohydrazidation reactions of beta,gamma-unsaturated N-acyl-N-tosylhydrazines readily afforded pyrazolidinone ring systems that contained a tetrasubstituted carbon center, and the primary amine of the N-acyl-N-tosylhydrazine was shown to be a soft nucleophile. The similar bromohydrazidation reaction of gamma,delta-unsaturated N-acyl-N-tosylhydrazine resulted in O-cyclization to give a lactone ring instead of N-cyclization to give a hydropyridazine ring system; however, the intramolecular hydrazidopalladation reaction predominantly afforded a hydropyridazine ring. The established catalytic hydrazidopalladation reaction was applicable to several multisubstituted alkenes to construct a tetrasubstituted carbon center possessing a nitrogen group.
  • Keiji Tanino, Takumasa Yamada, Fumihiko Yoshimura, Takanori Suzuki
    CHEMISTRY LETTERS 43 (5) 607 - 609 0366-7022 2014/05 [Refereed][Not invited]
     
    A series of 4-cyanoazulene derivatives 1-5 were synthesized from 4-cyanohexahydroazulen-l-one, which was efficiently obtained by the annulation of the seven-membered ring on the cyclopentenone skeleton via the divinylcyclopropane rearrangement. This synthetic protocol is also effective in preparing 1,1'-bi(4-cyanoazulene) (6) and its p-phenylene-extended derivative 7, which undergo multistage redox reactions exhibiting electrochemical amphotericity.
  • Fumihiko Yoshimura, Keiji Tanino, Masaaki Miyashita
    TETRAHEDRON LETTERS 55 (18) 2895 - 2903 0040-4039 2014/04 [Refereed][Not invited]
     
    This review provides a compilation of the most recent synthetic approaches and total syntheses of zoanthamine alkaloids, which are structurally unique heptacyclic marine natural products that display a range of interesting biological activities. This review is focused on synthetic methodologies for the construction of the three adjacent quaternary asymmetric carbon atoms on the cyclohexane ring (C-ring) of these compounds. The literature covered in this review dates from 2008 to the end of 2013. (C) 2014 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-SA license
  • Mami Kudo, Fumikatsu Kondo, Hideki Maekawa, Tadashi Shimizu, Masaaki Miyashita, Keiji Tanino
    TETRAHEDRON LETTERS 55 (6) 1192 - 1195 0040-4039 2014/02 [Refereed][Not invited]
     
    A stereoselective [5+2] cycloaddition reaction using a new five-carbon unit, that has a dicobalt acetylene complex moiety and an enol silyl ether moiety, was developed. In the presence of a Lewis acid, the five-carbon unit reacted with an enol triisopropylsilyl ether to give a 1-acetyl-2-silyoxycycloheptane derivative, in which the three contiguous substituents on the seven-membered ring arrange cis to each other. (C) 2014 Elsevier Ltd. All rights reserved.
  • Takahiro Hiramatsu, Motomasa Takahashi, Keiji Tanino
    TETRAHEDRON LETTERS 55 (6) 1145 - 1147 0040-4039 2014/02 [Refereed][Not invited]
     
    Tubiferal A, a triterpenoid isolated from myxomycete Tubifera dimorphotheca, exhibits a reversal effect of vincristine (VCR) resistance against VCR-resistant KB cell lines. The compound possesses a complex structure involving the 6-7-6-5 polycyclic carbon framework with various functional groups. The stereoselective synthesis of the right-hand segment of tubiferal A was achieved on the basis of the cyclopentene annulation method and the semi-pinacol rearrangement reaction of an epoxy alcohol for constructing the trans-fused 6-5 bicyclic skeleton possessing two quaternary carbon atoms at the angular positions. (C) 2013 Elsevier Ltd. All rights reserved.
  • Ryosuke Hanada, Katsuhiko Mitachi, Keiji Tanino
    TETRAHEDRON LETTERS 55 (5) 1097 - 1099 0040-4039 2014/01 [Refereed][Not invited]
     
    The stereoselective synthesis of a tricyclic model compound of taxane diterpenes was achieved. The eight-membered B ring was constructed on the basis of a [6+2] cycloaddition reaction of a dicobalt acetylene complex with an enol silyl ether of cyclohexanone. After conversion of the cobalt complex moiety to an epoxide and introduction of a 3-cyanopropyl group, the A ring was formed via an intramolecular cyclization reaction under basic conditions. (C) 2014 Elsevier Ltd. All rights reserved.
  • Genta Tadano, Koji Ishikura, Keiji Tanino
    HETEROCYCLES 87 (11) 2267 - 2281 0385-5414 2013/11 [Not refereed][Not invited]
     
    A new method for constructing tetrasubstituted pyrrolidine derivatives using the known beta-lactam as a chiral building block was developed. After construction of a carbapenem skeleton, the beta-lactam moiety was cleaved to afford a multi-substituted pyrrolidine. The present method was employed for the synthesis of A-315675 analogs.
  • Takumasa Yamada, Fumihiko Yoshimura, Keiji Tanino
    TETRAHEDRON LETTERS 54 (6) 522 - 525 0040-4039 2013/02 [Refereed][Not invited]
     
    An efficient synthetic method for 2-cyano-1,4-cycloheptadiene derivatives was developed on the basis of divinylcyclopropane rearrangement. The substrates were prepared from 2-vinylcyclopropanecarbonitrile and an alpha,beta-epoxysilane through a Peterson olefination. The resulting 2-cyano-1,4-cycloheptadiene underwent deprotonation at the doubly allylic methylene group to afford a novel cycloheptadienyl anion, a useful intermediate for synthesizing polycyclic compounds. (C) 2012 Elsevier Ltd. All rights reserved.
  • Ayumi Osawa, Akane Mera, Kosuke Namba, Keiji Tanino
    Synlett 24 (2) 207 - 210 0936-5214 2013 [Refereed][Not invited]
     
    New reactions for the transformation of 1-(oxiranylmethyl)-1,2,3-triazoles into 2-(oxiranylmethyl)-1,2,3-triazoles or alkanenitriles were established. Successive treatment of the substrate with triflic acid and t-BuOH afforded 4,6-dihydro-5-hydroxy-1,3a,6a-triazapentalene derivative. Under the influence of NaH, the bicyclic compound was converted into a 2-(oxiranylmethyl)-1,2,3- triazole or an alkanenitrile. The reaction pathway depends on the substituent pattern of the epoxide side chain. © Georg Thieme Verlag Stuttgart New York.
  • Fumihiko Yoshimura, Keiji Tanino, Masaaki Miyashita
    Yuki Gosei Kagaku Kyokaishi/Journal of Synthetic Organic Chemistry 71 (2) 124 - 135 0037-9980 2013 [Refereed][Not invited]
     
    The zoanthamine alkaloids isolated from the genus Zoanthus species during the last three decades constitute a distinctive family of marine metabolites. These natural products are characterized by the densely functionalized heptacyclic framework, as exemplified by the structures of norzoanthamine (1), zoanthamine (2), and zoanthenol (3), as well as their potent spectrum of unique biological properties such as promising antiosteoporotic properties. Their distinctive biological activities, combined with novel chemical structures, make this family of alkaloids extremely attractive targets for chemical synthesis. However, because of their densely function-alized complex structures, synthetic studies of zoanthamine alkaloids had seriously been impeded until we reached the first total synthesis of norzoanthamine. We describe herein our synthetic approach toward the total synthesis of zoanthamine alkaloids (1-3), focusing on how to tackle and overcome various synthetic challenges.
  • Kosuke Namba, Akane Mera, Ayumi Osawa, Eri Sakuda, Noboru Kitamura, Keiji Tanino
    ORGANIC LETTERS 14 (21) 5554 - 5557 1523-7060 2012/11 [Refereed][Not invited]
     
    A one-pot synthetic method was established for the preparation of 2,5-disubstituted-1,3a,6a-triazapentalenes. The fluorescence observation of the synthetic 2,5-disubstituted-1,3a,6a-triazapentalenes revealed that the introduction of a substituent at the C5 position allowed a substantial change in the fluorescence quantum yield with little effect on the fluorescence wavelength.
  • Kosuke Namba, Akane Mera, Ayumi Osawa, Eri Sakuda, Noboru Kitamura, Keiji Tanino
    ORGANIC LETTERS 14 (21) 5554 - 5557 1523-7060 2012/11 [Refereed][Not invited]
     
    A one-pot synthetic method was established for the preparation of 2,5-disubstituted-1,3a,6a-triazapentalenes. The fluorescence observation of the synthetic 2,5-disubstituted-1,3a,6a-triazapentalenes revealed that the introduction of a substituent at the C5 position allowed a substantial change in the fluorescence quantum yield with little effect on the fluorescence wavelength.
  • Kosuke Namba, Akane Mera, Ayumi Osawa, Eri Sakuda, Noboru Kitamura, Keiji Tanino
    ORGANIC LETTERS 14 (21) 5554 - 5557 1523-7060 2012/11 [Refereed][Not invited]
     
    A one-pot synthetic method was established for the preparation of 2,5-disubstituted-1,3a,6a-triazapentalenes. The fluorescence observation of the synthetic 2,5-disubstituted-1,3a,6a-triazapentalenes revealed that the introduction of a substituent at the C5 position allowed a substantial change in the fluorescence quantum yield with little effect on the fluorescence wavelength.
  • Ryuichi Fuchigami, Kosuke Namba, Keiji Tanino
    TETRAHEDRON LETTERS 53 (43) 5725 - 5728 0040-4039 2012/10 [Refereed][Not invited]
     
    A concise [4+3] cycloaddition reaction of pyrroles with 2-(silyloxy)allyl cations has been developed. The oxyallyl cations stabilized with a methylthio group or geminal methyl groups were generated from the corresponding allylic alcohols under the influence of a Bronsted acid (Tf2NH), respectively. The use of N-nosyl-protected pyrroles as the four-carbon unit was found to give tropinone derivatives in high yield. (C) 2012 Elsevier Ltd. All rights reserved.
  • Fumihiko Yoshimura, Keiji Tanino, Masaaki Miyashita
    ACCOUNTS OF CHEMICAL RESEARCH 45 (5) 746 - 755 0001-4842 2012/05 [Not refereed][Not invited]
     
    Zoanthamine alkaloids, isolated from organisms in the Zoanthus genus, constitute a distinctive family of marine metabolites. L These molecules exhibit a broad spectrum of unique biological properties. For example, norzoanthamine inhibits interleukin-6, the key mediator of bone resorption in osteoporosis, providing a promising drug candidate for a disease that affects more than 10 million people over age 50 in the United States. In addition, these natural products are characterized by a densely functionalized heptacyclic framework, as exemplified by the structures of zoanthamine, norzoanthamine, and zoanthenol, which makes them extremely attractive targets for chemical synthesis. Prior to our first total synthesis of norzoanthamine in 2004, the densely functionalized and complex stereostructures of the zoanthamine alkaloids had impeded synthetic studies of these molecules. In this Account, we describe our synthetic approach toward the total synthesis of zoanthamine alkaloids, focusing on how we overcame various synthetic challenges. At the beginning of our synthetic studies, we aimed to develop an efficient route that was flexible enough to provide access to several members of the family while allowing the synthesis of various analogues for biological testing. Our first project was the total synthesis of norzoanthamine, and we established an efficient synthetic route based on a novel strategy involving the following key features. First, we used a sequential three-component coupling reactions and subsequent photosensitized oxidation of a furan moiety to synthesize the precursor for the key intramolecular Diels-Alder reaction. Second, the key intramolecular Diels-Alder reaction constructed the ABC-ring carbon framework bearing two adjacent quaternary asymmetric carbon atoms at the C12 and C22 positions in a single stereoselective step. Third, we installed the third quaternary asymmetric carbon center at the C9 position by an intramolecular acylation of a keto alcohol followed by successive O-methylation and C-methylation reactions with complete stereoselectivity. Through the exploitation of a deuterium kinetic isoptope effect, we then efficiently synthesized the alkyne segment. Next, a coupling reaction between the alkyne segment and the amino alcohol segment and several subsequent synthetic transformations afforded the bis-aminoacetalization precursor. Finally, bis-aminoacetalization reactions carried out in one-pot constructed the DEFG-ring system and culminated in the total synthesis of norzoanthamine. Our synthetic route to norzoanthamine also allowed access to other zoanthamine alkaloids from a common synthetic intermediate, by way of stereoselective introduction of the C19 methyl group for zoanthamine, and isoaromatization for construction of the aromatic A-ring in zoanthenol. The chemistry described here not only allowed us to overcome formidable synthetic challenges but also opened a completely chemical avenue to naturally occurring zoanthamine alkaloids and their synthetic derivatives.
  • Kosuke Namba, Michika Kanaki, Hiroki Suto, Mugio Nishizawa, Keiji Tanino
    ORGANIC LETTERS 14 (5) 1222 - 1225 1523-7060 2012/03 [Refereed][Not invited]
     
    An efficient method for the construction of dihydroquinoline derivatives possessing a quaternary carbon center is developed by an application of Hg(OTf)(2)-catalyzed vinylogous semi-pinacol-type rearrangement. The reaction was found to be specifically catalyzed by mercury salt and to proceed via a bicyclic aminal.
  • Fumihiko Yoshimura, Makoto Torizuka, Genki Mori, Keiji Tanino
    SYNLETT (2) 251 - 254 0936-5214 2012/01 [Refereed][Not invited]
     
    An efficient method for constructing carbocycles with all-carbon quaternary stereocenters has been developed on the basis of a stereoselective cyclization reaction of alpha,beta-unsaturated lactones having an alkanenitrile side chain. Treatment of the substrate with lithium hexamethyldisilazide (LiHMDS) in the presence of triisopropylsilyl chloride (TIPSCl) led to the generation of the corresponding alpha-cyano carbanion species which readily underwent an intramolecular conjugate addition reaction. It was found that the combined use of trimethylsilyl trifluoromethanesulfonate (TMSOTf) and triethylamine is also effective for the cyclization reaction without using a strong base. Interestingly, different stereochemical outcomes were observed in the two cyclization methods.
  • Hiroaki Yagi, Yoshiro Chuman, Yuuki Kozakai, Toshiaki Imagawa, Yu Takahashi, Fumihiko Yoshimura, Keiji Tanino, Kazuyasu Sakaguchi
    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS 22 (1) 729 - 732 0960-894X 2012/01 [Refereed][Not invited]
     
    PPM1D is a p53-inducible Ser/Thr protein phosphatase. PPM1D gene amplification and overexpression have been reported in a variety of human tumors, including breast cancer and neuroblastoma. Because the phosphatase activity of PPM1D is essential for its oncogenic role, PPM1D inhibitors should be viable anti-cancer agents. In our current study, we showed that SPI-001 was a potent and specific PPM1D inhibitor. SPI-001 inhibited PPM1D phosphatase activity in PPM1D-overexpressing human breast cancer cells and increased phosphorylation of p53. Furthermore, SPI-001 suppressed cell proliferation by inducing apoptosis. Our present study suggested that SPI-001 was a potential lead compound in developing anti-cancer drugs. (C) 2011 Elsevier Ltd. All rights reserved.
  • Fumihiko Yoshimura, Ayano Kowata, Keiji Tanino
    ORGANIC & BIOMOLECULAR CHEMISTRY 10 (28) 5431 - 5442 1477-0520 2012 [Refereed][Not invited]
     
    We developed a new method for stereoselective construction of an all-carbon quaternary stereogenic center on a carbocyclic ring based on regio- and stereoselective S(N)2' alkylation reactions of gamma,delta-epoxy-alpha, beta-unsaturated cyclic ketones. Treatment of the ketones, which were readily prepared in enantiomerically pure form by means of aldol condensations between 3-ethoxy-2-cycloalkenones and alpha,beta-epoxy aldehydes, with a R2Zn-CuCN reagent afforded anti-S(N)2' products stereoselectively. Conversely, the corresponding syn-S(N)2' products were stereoselectively obtained through two-step transformations of the same gamma,delta-epoxy-alpha,beta-unsaturated cyclic ketones: (1) conversion of the epoxide moiety to a chlorohydrin by treatment with MgCl2 and (2) subsequent S(N)2' substitution of the chlorohydrin with a R2Zn-CuCN reagent. These substitution products with their chiral trans-allylic alcohol moieties are promising precursors for complex molecules. For example, Eschenmoser-Claisen rearrangement of one of the substitution products resulted in stereoselective formation of a keto amide having contiguous quaternary and tertiary stereogenic centers.
  • Kosuke Namba, Ayumi Osawa, Shoji Ishizaka, Noboru Kitamura, Keiji Tanino
    JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 133 (30) 11466 - 11469 0002-7863 2011/08 [Refereed][Not invited]
     
    An efficient and versatile method was established for the preparation of 1,3a,6a-triazapentalenes. The 1,3a,6a-triazapentalene skeleton without an additional fused ring system was discovered to be a compact and highly fluorescent chromophore, which exhibited various interesting fluorescent properties such as a noteworthy correlation of luminescent wavelength with the Hammett sigma(P) value and a strongly positive solvatofluorochromism.
  • Keiji Tanino, Motomasa Takahashi, Yoshihide Tomata, Hiroshi Tokura, Taketo Uehara, Takashi Narabu, Masaaki Miyashita
    NATURE CHEMISTRY 3 (6) 484 - 488 1755-4330 2011/06 [Refereed][Not invited]
     
    Cyst nematodes are troublesome parasites that live on, and destroy, a range of important host vegetable plants. Damage caused by the potato cyst nematode has now been reported in over 50 countries. One approach to eliminating the problem is to stimulate early hatching of the nematodes, but key hatching stimuli are not naturally available in sufficient quantities to do so. Here, we report the first chemical synthesis of solanoeclepin A, the key hatch-stimulating substance for potato cyst nematode. The crucial steps in our synthesis are an intramolecular cyclization reaction for construction of the highly strained tricyclo[5.2.1.0(1,6)] decane skeleton (DEF ring system) and an intramolecular Diels-Alder reaction of a furan derivative for the synthesis of the ABC carbon framework. The present synthesis has the potential to contribute to addressing one of the critical food issues of the twenty-first century.
  • Fumihiko Yoshimura, Yu Takahashi, Keiji Tanino, Masaaki Miyashita
    CHEMISTRY-AN ASIAN JOURNAL 6 (3) 922 - 931 1861-4728 2011/03 [Refereed][Not invited]
     
    The total synthesis of zoanthenol, a unique aromatic member of the zoanthamine alkaloids, which has exhibited potent anti-platelet activities on human platelet aggregation, is described in full detail. The key step involves a Bronsted acid-promoted isoaromatization in the AB ring system to install the crucial aromatic ring. We have not only succeeded in the first total synthesis of zoanthenol, but also established an alternative efficient synthetic route from the commercially available norzoanthamine hydrochloride to zoanthenol.
  • Koichiro Dota, Tadashi Shimizu, Shoji Hasegawa, Masaaki Miyashita, Keiji Tanino
    TETRAHEDRON LETTERS 52 (8) 910 - 912 0040-4039 2011/02 [Refereed][Not invited]
     
    An efficient method for constructing a 10-membered carbocycle with an oxygen bridge has been developed on the basis of a formal [6+4] cycloaddition reaction. Under the influence of EtAlCl2, a dicobalt hexacarbonyl acetylene complex possessing a benzoyloxy group and an allylsilane moiety reacted with furan to give a 11-oxabicyclo[6.2.1]undec-9-ene derivative. On treatment with iodine, the cycloadduct underwent decomplexation followed by rearrangement of the oxygen bridge to afford a 11-oxabicyclo[5.3.1]undeca-1,5-diene derivative. (C) 2010 Elsevier Ltd. All rights reserved.
  • Yagi Hiroaki, Chuman Yoshiro, Yoshimura Fumihiko, Tanino Keiji, Sakaguchi Kazuyasu
    Abstracts of Papers of the American Chemical Society 241 2011 [Refereed][Not invited]
  • Koichiro Fukuda, Masaaki Miyashita, Keiji Tanino
    TETRAHEDRON LETTERS 51 (34) 4523 - 4525 0040-4039 2010/08 [Refereed][Not invited]
     
    Practical methods for the synthesis of the optically active (E)- and (Z)-2-silyl-3-pentene-1-ols are described. The optically pure (E)-allylsilane was synthesized from commercially available (R)-3-butyn-2-ol in five steps involving hydrozirconation followed by alkylation of the resulting alkenylmetal with BnOCH(2)Cl. On the other hand, both enantiomers of the corresponding (Z)-allylsilane were prepared from commercially available dimethylphenylvinylsilane through epoxidation, the regioselective epoxide-opening reaction with 1-propynylmagnesium bromide, and the subsequent optical resolution using a lipase. (C) 2010 Elsevier Ltd. All rights reserved.
  • Yasuhiro Shiina, Yoshihide Tomato, Masaaki Miyashita, Keiji Tanino
    CHEMISTRY LETTERS 39 (8) 835 - 837 0366-7022 2010/08 [Refereed][Not invited]
     
    The asymmetric total synthesis of glycinoeclepin A, a hatch-stimulating agent of the soybean cyst nematode, was accomplished on the basis of a cyclopentene annulation for constructing the CD ring moiety having contiguous quaternary carbon atoms. Introduction of the A ring moiety was achieved by an alkylation reaction using a 7-oxabicyclo[2.2.1]hex-1-yl anion species.
  • Katsuhiko Mitachi, Tadashi Shimizu, Masaaki Miyashita, Keiji Tanino
    TETRAHEDRON LETTERS 51 (30) 3983 - 3986 0040-4039 2010/07 [Refereed][Not invited]
     
    An efficient formal [6+2] cycloaddition reaction of a new six-carbon unit with enol silyl ether was developed on the basis of a dicobalt hexacarbonyl propargyl cation species. Under the influence of EtAl-Cl(2), 6-benzoyloxy-2-(triisopropylsilyloxy)-1-hexen-4-yne-dicobalthexacarbonyl reacted with enol triisopropylsilyl ethers to yield 7-(triisopropylsilyloxy)-3-cyclooctyn-1-one-dicobalthexacarbonyl derivatives in good yield. The reactions with cyclic enol silyl ethers as well as acyclic enol silyl ethers exhibited remarkably high diastereoselectivity. (C) 2010 Elsevier Ltd. All rights reserved.
  • Katsuhiko Mitachi, Takashi Yamamoto, Fumikatsu Kondo, Tadashi Shimizu, Masaaki Miyashita, Keiji Tanino
    CHEMISTRY LETTERS 39 (6) 630 - 632 0366-7022 2010/06 [Refereed][Not invited]
     
    A new synthetic method for cycloheptanone derivatives was developed on the basis of a novel [5 + 2] cycloaddition reaction using a dicobalt hexacarbonyl propargyl cation species and a silyloxyallene. The method can be applied for constructing functionalized hydroazulene skeletons, and a total synthesis of sesquiterpene furanether B was achieved through the reactions involving transformation of the dicobalt acetylene complex into a maleic anhydride derivative and the crucial oxidative transannular ether ring formation.
  • Daisuke Nakagawa, Masaaki Miyashita, Keiji Tanino
    TETRAHEDRON LETTERS 51 (20) 2771 - 2773 0040-4039 2010/05 [Refereed][Not invited]
     
    A new method for constructing the ABCE ring system of azadirachtin in a stereoselective manner was developed. The synthesis of the model compound features (1) stereoselective construction of the highly hindered C8 quaternary center by an intermolecular addition reaction of an allylborane with an aldehyde and (2) construction of the E ring moiety by the Pd-catalyzed Nazarov cyclization. (C) 2010 Elsevier Ltd. All rights reserved.
  • Kosuke Namba, Kaori Kobayashi, Yoshiko Murata, Hiroko Hirakawa, Tohru Yamagaki, Takashi Iwashita, Mugio Nishizawa, Shoichi Kusumoto, Keiji Tanino
    ANGEWANDTE CHEMIE-INTERNATIONAL EDITION 49 (51) 9956 - 9959 1433-7851 2010 [Refereed][Not invited]
  • Kosuke Namba, Isamu Shoji, Mugio Nishizawa, Keiji Tanino
    ORGANIC LETTERS 11 (21) 4970 - 4973 1523-7060 2009/11 [Refereed][Not invited]
     
    An efficient and simple method for selective acylation of either one of two nitrogen atoms of tosylhydrazide was developed. The selectivity was drastically controlled by a catalytic amount of 4-aminopyridine or 4-(dimethylamino)pyridine with common acylating agents. The nitrogen atom masked with a tosyl group was acylated in the presence of 4-aminopyridine, whereas the primary nitrogen atom was acylated in the absence of 4-aminopyridine.
  • Fumihiko Yoshimura, Atsushi Matsui, Atsushi Hirai, Keiji Tanino, Masaaki Miyashita
    TETRAHEDRON LETTERS 50 (36) 5126 - 5129 0040-4039 2009/09 [Refereed][Not invited]
     
    A novel stereoselective S(N)2' alkylation reaction sequence of the gamma,delta-epoxy alpha,beta-unsaturated ester system has been developed which involves a regioselective substitution reaction with chloride ions at the gamma-position and a Subsequent S(N)2' alkylation reaction of the resulting gamma-chloro-delta-hydroxy derivatives with a R3Al-CuCN reagent. The new methodology was demonstrated to be applicable to a variety of substrates and to provide various delta-hydroxy-alpha-alkyl-beta,gamma-unsaturated esters including those bearing a quaternary asymmetric carbon atom at the alpha-position in a highly stereoselective manner and high yields. (C) 2009 Elsevier Ltd. All rights reserved.
  • Kosuke Namba, Yukari Kaihara, Hirofumi Yamamoto, Hiroshi Imagawa, Keiji Tanino, Robert M. Williams, Mugio Nishizawa
    CHEMISTRY-A EUROPEAN JOURNAL 15 (27) 6560 - 6563 0947-6539 2009 [Refereed][Not invited]
  • Yu Takahashi, Fumihiko Yoshimutra, Keiji Tanino, Masaaki Miyashita
    ANGEWANDTE CHEMIE-INTERNATIONAL EDITION 48 (47) 8905 - 8908 1433-7851 2009 [Refereed][Not invited]
  • Fumihiko Yoshimura, Minoru Sasaki, Izumi Hattori, Kei Komatsu, Mio Sakai, Keiji Tanino, Masaaki Miyashita
    CHEMISTRY-A EUROPEAN JOURNAL 15 (27) 6626 - 6644 0947-6539 2009 [Refereed][Not invited]
     
    The zoanthamine alkaloids, a type of heptacyclic marine alkaloid isolated from colonial zoanthids of the genus Zoanthus sp., have distinctive biological and pharmacological properties in addition to their unique chemical structures with stereochemical complexity. Namely, norzoanthamine (1) can suppress the loss of bone weight and strength in ovariectomized mice and has been expected as a promising candidate for a new type of antiosteoporotic drug, while zoanthamine (2) has exhibited potent inhibitory activity toward phorbol myristate-induced inflammation in addition to powerful analgesic effects. Recently, norzoanthamine derivatives were demonstrated to inhibit strongly the growth of P-388 murine leukemia cell lines, in addition to their potent antiplatelet activities on human platelet aggregation. Their distinctive biological properties, combined with novel chemical structures, make this family of alkaloids extremely attractive targets for chemical synthesis. However, the chemical synthesis of the zoanthamine alkaloids has been impeded owing to their densely functionalized complex stereostructures. In this paper, we report the first and highly efficient total syntheses of norzoanthamine (1) and zoanthamine (2) in full detail, which involve stereoselective synthesis of the requisite triene (18) for an intramolecular Diels-Alder reaction via the sequential three-component coupling reactions, the key intramolecular Diels-Alder reaction, and subsequent crucial bis-aminoacetalization as the key steps. Ultimately, we achieved the total synthesis of norzoanthamine (1) in 41 steps with an overall yield of 3.5% (an average of 92% yield each step) and that of zoanthamine (2) in 43 steps with an overall yield of 2.2% (an average of 91% yield each step) starting from (R)-5-methylcyclohexenone (3), respectively.
  • Fumihiko Yoshimura, Masaki Takahashi, Keiji Tanino, Masaaki Miyashita
    HETEROCYCLES 77 (1) 201 - 206 0385-5414 2009/01 [Refereed][Not invited]
     
    A novel and efficient synthetic method for 3-bromofuran derivatives via stereoselective cyclization of gamma,delta-epoxy-(E)-alpha-bromoacrylates is described. The reaction of a gamma,delta-epoxy-(E)-alpha-bromoacrylate with MeAl(3)-H(2)O gave rise to a 3-bromo-2-methylfuran derivative, i.e., methylated bromofuran at the 2-position, while the reaction with Me(3)Al-(CF(3))(2)CHOH reagent produced a 2-alkoxy-3-bromofuran derivative in high yield. The 3-bromofuran obtained was transformed into various functionalized furan derivatives.
  • Xiao-Qiang Yu, Fumihiko Yoshimura, Keiji Tanino, Masaaki Miyashita
    TETRAHEDRON LETTERS 49 (52) 7442 - 7445 0040-4039 2008/12 [Refereed][Not invited]
     
    The unprecedented, stereospecific interconversion of cis- and trans-gamma,delta-epoxy alpha,beta-unsaturated ester systems has been realized, which involves the palladium-catalyzed stereospecific alkoxy or hydroxy substitution reaction with double inversion of configuration at the gamma-position as the key step. The new methodology is not only applicable to various disubstituted and trisubstituted epoxy unsaturated esters, but also these interconversions proceed with an extremely high degree of stereoselectivity and efficiency. (C) 2008 Elsevier Ltd. All rights reserved.
  • Fumihiko Yoshimura, Masaki Takahashi, Keiji Tanino, Masaaki Miyashita
    TETRAHEDRON LETTERS 49 (49) 6991 - 6994 0040-4039 2008/12 [Refereed][Not invited]
     
    Tire stereospecific epoxide-opening reactions of 1,1-dibromo-3,4-epoxy-1-alkenes with allyltributylst-annane and with ketene silyl acetals in the presence of a Lewis acid are described. Both the reactions occurred regioselectively at the allylic position via an S(N)2 process giving rise to a single product respectively. Treatment of the products by the latter reaction with p-TsOH afforded various 3 4-anti- and 3 4-syn-disubstituted gamma-lactones in a highly stereoselective manner and high yields. (C) 2008 Elsevier Ltd. All rights reserved.
  • Xiao-Qiang Yu, Fumihiko Yoshimura, Fumito Ito, Minoru Sasaki, Atsushi Hirai, Keiji Tanino, Masaaki Miyashita
    ANGEWANDTE CHEMIE-INTERNATIONAL EDITION 47 (4) 750 - 754 1433-7851 2008 [Refereed][Not invited]
  • K Tanino, K Arakawa, M Satoh, Y Iwata, M Miyashita
    TETRAHEDRON LETTERS 47 (6) 861 - 864 0040-4039 2006/02 [Refereed][Not invited]
     
    A novel cyclization reaction of a 1,1-dibromoalkene derivative having an alpha,beta-unsaturated ester moiety was developed. Under the influence of Me2CuLi, the 1,1-dibromoalkene was converted into a (Z)-vinylcopper species which in turn underwent an intramolecular conjugate addition reaction with the alpha,beta-unsaturated ester moiety. Five-, six-, and seven-membered carbocycles were constructed by the present method. The substrate having an epoxide moiety also afforded a five-membered product via a 5-exo type intramolecular cyclization reaction. (c) 2005 Elsevier Ltd. All rights reserved.
  • K Tanino, Y Tomata, Y Shiina, M Miyashita
    EUROPEAN JOURNAL OF ORGANIC CHEMISTRY (2) 328 - 334 1434-193X 2006/01 [Refereed][Not invited]
     
    A new cyclopentene annulation method based on a conjugate addition reaction with 4-methoxybut-3-enenitrile was developed. Treatment of a cyclic enone with the potassium carbanion of the nitrile followed by acetic anhydride afforded an enol acetate, which underwent an HCl-mediated intramolecular cyclization reaction to yield a bicyclo[n.3.0]alkenone derivative in good yield. A lipase-mediated optical resolution of the annulation product provided a new chiral building block for steroids and. other natural compounds. ((c) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006).
  • Kuwajima, I, K Tanino
    CHEMICAL REVIEWS 105 (12) 4661 - 4670 0009-2665 2005/12 [Not refereed][Not invited]
     
    A review on the development of methodologies for constructing the trans-bicyclo[4.4.1]undecane framework that aims the total synthesis of ingenol is presented. Ingenols have shown remarkable biological properties to mimic diacylglycerol and function as endogenous activators of protein kinase, and were found to exhibit antitumor or tumor-promoting, antileukemic, and anti-HIV properties. Different synthetic approaches toward ingenol discussed, which includes: exploration of a tandem cyclization/rearrangement methodologies, deprotonation methodology, Kigoshi's approach, and Wood's approach.
  • R Nakamura, K Tanino, M Miyashita
    ORGANIC LETTERS 7 (14) 2929 - 2932 1523-7060 2005/07 [Refereed][Not invited]
     
    The first synthesis of premisakinolide A, the monomeric counterpart of misakinolide A, the marine 40-membered macrolide displaying potent activity against a variety of human carcinoma cell lines, has been reported. The strategy was highlighted by a crucial coupling of a tetrahydropyran fragment and an alkynylaluminum reagent having a polypropionate chain, the highly stereoselective cross aldol reaction of segment A and segment B, and the stereospecific construction of the polypropionate structure based on original acyclic stereocontrol.
  • Y Iwata, K Tanino, M Miyashita
    ORGANIC LETTERS 7 (12) 2341 - 2344 1523-7060 2005/06 [Refereed][Not invited]
     
    A highly stereoselective synthesis of the C(13)-C(23) segment of tedanolide (1), an 18-membered macrolide isolated from the Caribbean sponge Tedania ignis, displaying significant cytotoxicity against KB and PS tumor cell lines, is described which involves two stereoselective epoxidations of regioisomeric trisubstituted double bonds and a stereospecific S(N)2′ methylation reaction of a trans-γ,δ-epoxy-cis-α,6-unsaturated ester as the key steps.
  • Y Iwata, N Maekawara, K Tanino, M Miyashita
    ANGEWANDTE CHEMIE-INTERNATIONAL EDITION 44 (10) 1532 - 1536 1433-7851 2005/02 [Refereed][Not invited]
  • K Tanino, K Aoyagi, Y Kirihara, Y Ito, M Miyashita
    TETRAHEDRON LETTERS 46 (7) 1169 - 1172 0040-4039 2005/02 [Refereed][Not invited]
     
    A new synthetic method of cyclobutanone derivatives and four-membered enol ethers via an intramolecular cyclization of a ketone enolate was developed. The cyclization precursors, enol triflates having a silyloxy group at the beta'-position, were synthesized from the corresponding beta-hydroxy ketones, which were prepared via an aldol reaction of a cycloalkanone and an aldehyde. Under the influence of TBAF, the enol triflates afforded a cyclobutanone or a four-membered enol ether through rearrangement of the trifluoromethanesulfonyl group followed by an intramolecular C - or O-alkylation reaction. (C) 2004 Elsevier Ltd. All rights reserved.
  • M Miyashita, T Mizutani, G Tadano, Y Iwata, M Miyazawa, K Tanino
    ANGEWANDTE CHEMIE-INTERNATIONAL EDITION 44 (32) 5094 - 5097 1433-7851 2005 [Refereed][Not invited]
  • Masaaki Miyashita, Keiji Tanino
    Yuki Gosei Kagaku Kyokaishi/Journal of Synthetic Organic Chemistry 62 1080 - 1093 0037-9980 2004/11/01 [Not refereed][Not invited]
     
    There have been found in nature a variety of polypropionate-derived natural products exhibiting potent pharmacological properties as well as biological activities, as exemplified by various antibiotics that have played clinically important roles. In order to synthesize these natural products stereoselectively and to open a completely chemical avenue to these compounds and their analogues, stereospecific construction methodologies for acyclic organic molecules bearing contiguous asymmetric carbon atoms are of critical importance. In this article, the development of new types of acyclic stereocontrol and their application to natural product synthesis are described, in which stereoselective total syntheses of zincophorin, the ionophore antibiotic, and a potent antitumor marine natural product, scytophycin C, a 22-membered macrolide with structural and stereochemical complexity, are discussed.
  • M Miyashita, K Tanino
    JOURNAL OF SYNTHETIC ORGANIC CHEMISTRY JAPAN 62 (11) 1080 - 1094 0037-9980 2004/11 [Refereed][Not invited]
     
    There have been found in nature a variety of polypropionate-derived natural products exhibiting potent pharmacological properties as well as biological activities, as exemplified by various antibiotics that have played clinically important roles. In order to synthesize these natural products stereo selectively and to open a completely chemical avenue to these compounds and their analogues, stereospecific construction methodologies for acyclic organic molecules bearing contiguous asymmetric carbon atoms are of critical importance. In this article, the development of new types of acyclic stereocontrol and their application to natural product synthesis are described, in which stereoselective total syntheses of zincophorin, the ionophore antibiotic, and a potent antitumor marine natural product, scytophycin C, a 22-membered macrolide with structural and stereochemical complexity, are discussed.
  • M Miyashita, M Sasaki, Hattori, I, M Sakai, K Tanino
    SCIENCE 305 (5683) 495 - 499 0036-8075 2004/07 [Refereed][Not invited]
     
    Norzoanthamine, an alkaloid isolated from Zoanthus sp., can suppress the loss of bone weight and strength in ovariectomized mice. Norzoanthamine derivatives can also strongly inhibit the growth of P-388 murine leukemia cell lines and human platelet aggregation. However, norzoanthamine's densely functionalized complex stereostructure and scarce availability from natural sources have proved a synthetic challenge. We report the stereoselective total synthesis of norzoanthamine in 41 steps, with an overall yield of 3.5% ( an average of 92% yield each step).
  • M Sasaki, M Hatta, K Tanino, M Miyashita
    TETRAHEDRON LETTERS 45 (9) 1911 - 1913 0040-4039 2004/02 [Refereed][Not invited]
     
    Regio- and stereospecific alkyl and alkynyl substitution reactions of epoxy selenides with organoaluminum reagents have been developed, which proceed via episelenonium ion intermediates to give the C2 alkyl substitution products with double inversion of the configuration and the C1 alkynyl substitution products with migration of the arylseleno group in high yields, respectively. (C) 2004 Elsevier Ltd. All rights reserved.
  • K Komatsu, K Tanino, M Miyashita
    ANGEWANDTE CHEMIE-INTERNATIONAL EDITION 43 (33) 4341 - 4345 1433-7851 2004 [Refereed][Not invited]
  • Yoshihide Tomata, Minoru Sasaki, Keiji Tanino, Masaaki Miyashita
    Tetrahedron Letters 44 (50) 8975 - 8977 0040-4039 2003/12/08 [Refereed][Not invited]
     
    The first C2 selective halide substitution reactions of 2,3-epoxy alcohols have been realized by the use of the (CH3O)3B-MX (X=I, Br, Cl) system, which proceed through novel endo-mode epoxide-opening of intramolecular boron chelates to afford the corresponding C2 halohydrin derivatives with high regio- and stereoselectivity. © 2003 Elsevier Ltd. All rights reserved.
  • R Nakamura, K Tanino, M Miyashita
    ORGANIC LETTERS 5 (20) 3583 - 3586 1523-7060 2003/10 [Refereed][Not invited]
     
    Stereoselective syntheses of the C(l)-C(18) segment (segment A) and the C(19)-C(31) segment (segment B) are described in the preceding paper. This paper reports the key coupling reaction of both segments, 22-membered lactonization, and the crucial terminal amidation reaction culminating in the total synthesis of scytophycin C.
  • R Nakamura, K Tanino, M Miyashita
    ORGANIC LETTERS 5 (20) 3579 - 3582 1523-7060 2003/10 [Refereed][Not invited]
     
    Stereoselective total synthesis of scytophycin C, a marine 22-membered macrolide displaying potent activity against a variety of human carcinoma cell lines, has been reported in which the polypropionate structure bearing contiguous asymmetric centers was stereospecifically constructed by using new acyclic stereocontrol. This paper describes stereoselective syntheses of the C(l)-C(18) segment (Segment A) including a trans-disubstituted dihydropyran ring and the C(19)-C(31) segment (Segment 13) having eight stereogenic centers.
  • M Sasaki, K Tanino, A Hirai, M Miyashita
    ORGANIC LETTERS 5 (10) 1789 - 1791 1523-7060 2003/05 [Refereed][Not invited]
     
    [GRAPHICS] Highly efficient C2 selective substitution reactions of 2,3-epoxy alcohols with nucleophiles were developed by using NaN3-(CH3O)(3)B, NaSPh(CH3O)(3)B, or NaCN-(C2H5O)(3)B system. The reaction proceeds through novel endo-mode epoxide opening of an intramolecular boron chelate, which was suggested from both experimental and quantum mechanic studies.
  • K Tanino, K Onuki, K Asano, M Miyashita, T Nakamura, Y Takahashi, Kuwajima, I
    JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 125 (6) 1498 - 1500 0002-7863 2003/02 [Refereed][Not invited]
  • A Hirai, T Tonooka, K Tanino, M Miyashita
    CHIRALITY 15 (1) 108 - 109 0899-0042 2003/01 [Refereed][Not invited]
     
    A new synthetic methodology for aldoses and aldonitols was developed in which two stereospecific epoxide-opening reactions with double inversion of the configuration, i.e., the ring-opening reaction of epoxy sulfides with phenylboronic acid and the stereospecific interconversion of trans- and cis-epoxy sulfides, were designed as the key steps. The synthetic potential of the new methodology was exemplified by the highly stereoselective synthesis of two pentose-derived sugars, arabitol and adonitol (ribitol). (C) 2002 Wiley-Liss, Inc.
  • A Hirai, T Tonooka, K Tanino, M Miyashita
    CHIRALITY 15 (1) 108 - 109 0899-0042 2003/01 [Refereed][Not invited]
     
    A new synthetic methodology for aldoses and aldonitols was developed in which two stereospecific epoxide-opening reactions with double inversion of the configuration, i.e., the ring-opening reaction of epoxy sulfides with phenylboronic acid and the stereospecific interconversion of trans- and cis-epoxy sulfides, were designed as the key steps. The synthetic potential of the new methodology was exemplified by the highly stereoselective synthesis of two pentose-derived sugars, arabitol and adonitol (ribitol). (C) 2002 Wiley-Liss, Inc.
  • K Tanino, F Kondo, T Shimizu, M Miyashita
    ORGANIC LETTERS 4 (13) 2217 - 2219 1523-7060 2002/06 [Refereed][Not invited]
     
    A [5 + 2] cycloaddition reaction of a new five-carbon unit was developed on the basis of a dicobalt hexacarbonyl propargyl cation species. Under the influence of EtAlCl2, [5-benzoyloxy-2-(triisopropylsiioxy)-1-penten-3-yne)]dicobalt hexacarbonyl reacted with enol triisopropylsilyl ethers to yield seven-membered dicobalt acetylene complexes in good yield. The reactions with cyclic enol silyl ethers as well as acyclic enol siiyl ethers exhibited remarkably high diastereoselectivity. The cycloadducts can be easily converted into various kinds of cycloheptanone derivatives.
  • M Sakai, M Sasaki, K Tanino, M Miyashita
    TETRAHEDRON LETTERS 43 (9) 1705 - 1708 0040-4039 2002/02 [Refereed][Not invited]
     
    Stereoselective synthesis of the ABC ring system of norzoanthamine having five asymmetric centers including two quaternary carbon atoms has been successfully accomplished by an intramolecular Diels-Alder reaction. A key intermediate for the Diets-Alder reaction was efficiently and stereoselectively synthesized by a tandem conjugate addition-aldol strategy and subsequent photosensitized oxidation of a furan derivative. (C) 2002 Elsevier Science Ltd. All rights reserved.
  • Hirai A, Tonooka T, Wakatsuki K, Tanino K, Miyashita M
    Angewandte Chemie-International Edition 41 (5) 819 - + 2002 [Refereed][Not invited]
  • A Hirai, A Matsui, K Komatsu, K Tanino, M Miyashita
    CHEMICAL COMMUNICATIONS (17) 1970 - 1971 1359-7345 2002 [Refereed][Not invited]
     
    A highly regio- and stereoselective alpha-methylation reaction of gamma, delta-epoxy-alpha, beta-unsaturated esters was achieved by using a Me2Zn-CuCN reagent.
  • M Sasaki, K Tanino, M Miyashita
    JOURNAL OF ORGANIC CHEMISTRY 66 (16) 5388 - 5394 0022-3263 2001/08 [Refereed][Not invited]
     
    A regioselective and stereospecific substitution reaction of 1-(phenylthio)-2,3-epoxyalkanes was achieved by using organoaluminum. reagents as a nucleophile. Under the influence of trimethyl- or triethylaluminum, a 1-(phenylthio)-2,3-epoxyalkane underwent substitution at the C2 position to give a product with retention of the configuration. The reaction proceeds through an episulfonium ion intermediate, which gives rise to the C2-substitution products with double inversion of the configuration. Introduction of an alkynyl group was also accomplished by the reaction with dimethyl[2-(trimethylsilyl)ethynyl]aluminum in dichloromethane.
  • K Tanino
    JOURNAL OF SYNTHETIC ORGANIC CHEMISTRY JAPAN 59 (6) 549 - 559 0037-9980 2001/06 [Refereed][Not invited]
     
    New synthetic methods for functionalized carbocyclic compounds were developed on the basis of [3+2] and [5+2] cycloaddition reactions by using carbocation species. Under the influence of a Lewis acid, 3-(methylthio)-2-siloxyallyl acetates reacted with various kinds of olefins to afford the corresponding cyclopentanones in good yields. The sterically more hindered regioisomer was predominantly formed in every case, and surprisingly high stereoselectivity was also observed in certain cases. An efficient synthetic method for (-)-coriolin has been developed on the basis of the [3+2] cycloaddition reaction. On the other hand, 5-acetozy-2-[(trimethylsilyl)methyl]-1-penten-3-yne-dicobalthexacarbonyl underwent [5+2] cycloaddition reactions with enol triisopropylsilyl ethers to give seven-membered compounds. The reactions with cyclic enol silyl ethers as well as acyclic enol silyl ethers exhibited remarkably high diastereoselectivity.
  • M Sasaki, K Tanino, M Miyashita
    ORGANIC LETTERS 3 (11) 1765 - 1767 1523-7060 2001/05 [Refereed][Not invited]
     
    Unprecedented nucleophilic substitution reactions of 2,3-epoxy-1-alkanols with alkyl and alkynylaluminum ate complexes have been studied and demonstrated to occur at the C2 position with extremely high stereoselectivity, i.e., with exactly reversed regioselectivity to that obtained in the substitution reactions by normal organoaluminum reagents, resulting in the formation of the C2-alkyl and C2-alkynyl substitution products in excellent yields.
  • K Tanino, Y Honda, M Miyashita
    TETRAHEDRON LETTERS 41 (48) 9281 - 9285 0040-4039 2000/11 [Refereed][Not invited]
     
    Intramolecular substitution reactions of 1-(alkynylsiloxy)-2,3-epoxyalkanes under acidic or basic conditions were investigated. In the presence of t-butyllithium, cyclic allenylsilanes, which can be easily converted to the corresponding allenes, were obtained in good yields. The regioselectivity was highly dependent on the configuration of the epoxide moiety, which was rationalized by assuming chair-like transition state models of the 6-endo type cyclization reactions. (C) 2000 Elsevier Science Ltd. All rights reserved.
  • T Shimizu, K Tanino, Kuwajima, I
    TETRAHEDRON LETTERS 41 (30) 5715 - 5718 0040-4039 2000/07 [Refereed][Not invited]
     
    Intramolecular hetero Diels-Alder reactions of alpha-(alkynylsiloxy)aldimine derivatives were developed, alpha-(Alkynylsiloxy)aldehydes, which were prepared from 1,2-alkanediols in two steps, were converted into the corresponding biscarbamates or N-arylimines. In the presence of BF3. OEt2, the biscarbamates afforded oxazine derivatives in high diastereo selectivity. On the other hand, quinoline derivatives were obtained in good yields by treating the N-arylimines with trifluoromethanesulfonic acid. (C) 2000 Elsevier Science Ltd. All rights reserved.
  • K Tanino, T Shimizu, M Miyama, Kuwajima, I
    JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 122 (25) 6116 - 6117 0002-7863 2000/06 [Refereed][Not invited]
  • Y Egami, M Takayanagi, K Tanino, Kuwajima, I
    HETEROCYCLES 52 (2) 583 - 586 0385-5414 2000/02 [Refereed][Not invited]
     
    Regiocontrol in ring opening reactions of 2-alkyl-4,4-dimethyl-1,3-dioxolane with allyltrimethylsilane was investigated. In the reactions promoted by TiCl4, the ratio of the isomers can be changed from 91:9 to 1:99 simply by adopting different experimental procedures based on the sequence of adding the substrates.
  • M Sasaki, M Miyazawa, K Tanino, M Miyashita
    TETRAHEDRON LETTERS 40 (52) 9267 - 9270 0040-4039 1999/12 [Refereed][Not invited]
     
    A stereoselective alkynylation reaction of trans-1-phenylthio-2,3-epoxyalkanes with alkynylaluminums which proceeds via episulfonium ions, that is, with double inversion of con figuration, has been developed. (C) 1999 Elsevier Science Ltd. All rights reserved.
  • N Watanabe, K Tanino, Kuwajima, I
    TETRAHEDRON LETTERS 40 (46) 8133 - 8136 0040-4039 1999/11 [Refereed][Not invited]
     
    A convenient annulation method for the synthesis of bicyclic enones from cycloalkanones was developed. In the presence of a Pd(0) catalyst, enol triflates derived from ethyl 2-oxocycloalkanecarboxylates were treated with 3-(ethoxycarbonyl)propylzinc iodide to afford the corresponding diesters via a cross-coupling reaction. The diesters were easily transformed into Delta(1,6)-bicyclo[4.n.0]alken-2-ones through Dieckmann condensation followed by decarboxylation. The annulation method was also applicable for the synthesis of the corresponding cycloheptenone derivative. (C) 1999 Elsevier Science Ltd. All rights reserved.
  • K Masuya, K Tanino, Kuwajima, I
    SYNLETT (5) 647 - 649 0936-5214 1999/05 [Refereed][Not invited]
     
    A new synthetic method for medium and large-sized carbocycles has been developed. An acyclic compound having an olefin moiety and a 3-(methylthio)allyl acetate moiety at each of the terminal positions was designed as a cyclization precursor. The corresponding allyl cation intermediate, which was generated by treatment with EtAlCl2, underwent cyclization via an intramolecular addition reaction. The ring size of the product, which depends on the reaction site of the allyl cation, can be controlled by changing the nucleophilicity of the terminal olefin moiety.
  • H Mizuno, K Domon, K Masuya, K Tanino, Kuwajima, I
    JOURNAL OF ORGANIC CHEMISTRY 64 (8) 2648 - 2656 0022-3263 1999/04 [Refereed][Not invited]
     
    An efficient synthetic method for (-)-coriolin has been developed on the basis of a [3+2] cycloaddition reaction of a 1-( methylthio)-2-siloxyallyl cationic species and vinylsulfides. An enantiomerically pure C-ring unit was prepared through optical resolution of five-membered allyl ester 6b using a lipase. The first [3+2] cycloaddition reaction of C-ring unit (S)-7 gave bicyclic ketones 8 and 9, which were easily converted into vinyl sulfide 11. Stereoselective construction of the A-ring was achieved by the second [3+2] cycloaddition reaction of the BC-ring unit. New methods for introduction of the oxygen functional groups to the triquinane skeleton were also developed for the last stages of the total synthesis. Thus, the C7 hydroxyl group was introduced by epoxidation of dienol silyl ether 17, and stereocontrolled construction of the spiro epoxide moiety was accomplished on the basis of a Darzens-type reaction.
  • K Tanino, T Shimizu, M Kuwahara, Kuwajima, I
    JOURNAL OF ORGANIC CHEMISTRY 63 (8) 2422 - 2423 0022-3263 1998/04 [Refereed][Not invited]
  • K Masuya, K Domon, K Tanino, Kuwajima, I
    JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 120 (8) 1724 - 1731 0002-7863 1998/03 [Refereed][Not invited]
     
    A new synthetic method for functionalized cyclopentanones was developed on the basis of a [3+2] cycloaddition reaction of a 1-(methylthio)-2-siloxyallyl cationic species and olefins. Allyl acetates 1a and 1b. which are the precursors of the allyl cationic species, are easily prepared in three or four steps from commercially available compounds. Under the influence of EtAlCl2 or AlCl3, 1a or 1b reacted with various kinds of olefins such as enol ethers, vinyl sulfides, styrenes, and trialkylolefins to afford the corresponding cyclopentanones in good yields. It is noteworthy that the sterically more hindered regioisomer was predominantly formed in every case. Furthermore, the reactions of 1b with vinyl sulfides exhibited surprisingly high stereoselectivity, which can be rationalized by the six-membered transition state models involving an orbital interaction between the sulfur atom of the vinyl sulfide and the alpha-carbon of the allyl cation.
  • K Tanino, N Yoshitani, F Moriyama, Kuwajima, I
    JOURNAL OF ORGANIC CHEMISTRY 62 (13) 4206 - 4207 0022-3263 1997/06 [Refereed][Not invited]
  • T Nakamura, T Matsui, K Tanino, Kuwajima, I
    JOURNAL OF ORGANIC CHEMISTRY 62 (10) 3032 - 3033 0022-3263 1997/05 [Refereed][Not invited]
  • K Domon, K Masuya, K Tanino, Kuwajima, I
    TETRAHEDRON LETTERS 38 (3) 465 - 468 0040-4039 1997/01 [Refereed][Not invited]
     
    Formal total synthesis of coriolin has been accomplished on the basis of a [3+2] cycloaddition reaction of a vinylsulfide with 3-(methylthio)-2-siloxyallyl cation. A five-membered vinylsulfide as a C ring unit was prepared in five steps from commercially available compounds. The first [3+2] cycloaddition reaction gave the BC ring intermediate, which was then converted into a bicyclic vinylsulfide in three steps. The construction of the A ring by the second [3+2] cycloaddition reaction followed by two-step-conversion afforded the tricyclic enone (30% overall yield from isobutyronitrile) which has previously been synthesized and converted into coriolin. Copyright (C) 1996 Elsevier Science Ltd
  • Keiji Tanino, Isao Kuwajima
    Phosphorus, Sulfur and Silicon and Related Elements 120-121 369 - 370 1042-6507 1997 [Refereed][Not invited]
     
    Highly stereoselective C-C bond forming reactions were developed on the basis of nucleophilic addition of alkenylsulfides to aldehydes, imines, and α,β-unsaturated carbonyl compounds.
  • Sugai M, Tanino K, Kuwajima I
    Synlett (5) 461 - & 1997 [Refereed][Not invited]
  • Kuwajima, I, K Tanino
    JOURNAL OF SYNTHETIC ORGANIC CHEMISTRY JAPAN 54 (11) 929 - 940 0037-9980 1996/11 [Not refereed][Not invited]
     
    By utilizing the characteristic features of vinylsulfides, 2-(alkylthio)allyl silyl ethers were designed as efficient ene substrates, and their use led to exploration of general carbonyl and imine ene reactions. By using 3-(alkylthio)-2-siloxyallyl acetates, a useful [3 + 2]cyclopentane annulation methodology was developed. Further, a tandem C-C bond formation/cleavage methodology was also designed.
  • Y Takahashi, K Tanino, Kuwajima, I
    TETRAHEDRON LETTERS 37 (33) 5943 - 5946 0040-4039 1996/08 [Refereed][Not invited]
     
    A new method for methylenecyclopentane annulation via formal [3+2] cycloaddition reaction was developed. Under the influence of Lewis acids, enol ethers and vinylsulfides were treated with 1-(alkylthio)-2-(trimethylsilylmethyl)ally esters 1a or 1b to afford methylenecyclopentanes in good yields. The reaction proceeds with almost complete regioselectivity as well as high stereoselectivity. Copyright (C) 1996 Elsevier Science Ltd
  • KMK Domon, K Tanino, Kuwajima, I
    SYNLETT (2) 157 - 158 0936-5214 1996/02 [Refereed][Not invited]
     
    A new synthetic method for cyclopentanone derivatives via formal [3+2] cycloaddition reaction of 2-oxyallyl cation and an alkene was developed. Under the influence of EtAlCl(2) or AlCl3, 3-acetoxy-1-(methylthio)-2-(triisopropylsiloxy)-1-propene or 1-acetoxy- 3-(methylthio)-2-(triisopropylsiloxy)-2-tridecene reacted with various kinds of alkenes to afford 2-(methylthio)cyclopentanone derivatives in good yield. The reaction was highly regioselective to yield the sterically more hindered regioisomer, which indicates that the initial C-C bond formation reaction between an alkene and the (1-(methylthio)-2-siloxy)allyl cation intermediate occurs at the gamma-position of sulfur.
  • Isao Kuwajima, Keiji Tanino
    Yuki Gosei Kagaku Kyokaishi/Journal of Synthetic Organic Chemistry 54 (11) 929 - 940 0037-9980 1996 [Refereed][Not invited]
     
    By utilizing the characteristic features of vinylsulfides, 2-(alkylthio)allyl silyl ethers were designed as efficient ene substrates, and their use led to exploration of general carbonyl and imine ene reactions. By using 3-(alkylthio)-2-siloxyallyl acetates, a useful [3+2]cyclopentane annulation methodology was developed. Further, a tandem C-C bond formation/cleavage methodology was also designed.
  • Sato K, Koga T, Masuya K, Tanino K, Kuwajima I
    Synlett (8) 751 - & 1996 [Refereed][Not invited]
  • M TAKAYANAGI, K TANINO, KUWAJIMA, I
    SYNLETT (2) 173 - 174 0936-5214 1995/02 [Refereed][Not invited]
     
    A highly stereoselective conjugate addition reaction with a,a-unsaturated aldehydes was developed by using alkenylsulfide as a nucleophile. Under the influence of TiCl3((OPr)-Pr-i), (1S*,2S*)-1-butyl-2-[(1Z)-1-(methylthio)propenyl]-1-(triethylsiloxy)cyclopentane reacted with enals to give 11,12-dimethyl-10-(methylthio)-14-(triethylsiloxy)-9,13-tetradecadien-5-one derivatives in >99% anti selectivity. The high regio- and stereoselection can be explained by assuming the chair-like six-membered cyclic transition state involving the orbital interaction between the sulfur and a carbonyl carbon.
  • K MASUYA, K TANINO, KUWAJIMA, I
    TETRAHEDRON LETTERS 35 (43) 7965 - 7968 0040-4039 1994/10 [Refereed][Not invited]
     
    In the presence of Me(2)AlCl, reactions of the title compounds with a variety of aldehydes proceeded with high efficacy of chirality transfer to give the corresponding optically pure ene adducts, which could be converted to the gamma-lactones, eg., rove beetle pheromone.
  • Y TOHYAMA, K TANINO, KUWAJIMA, I
    JOURNAL OF ORGANIC CHEMISTRY 59 (3) 518 - 519 0022-3263 1994/02 [Refereed][Not invited]
     
    A stereoselective ene reaction of aldimines with 2-(alkylthio)allyl silyl ethers was developed. Under the influence of Lewis acids, N-acylimine or geminal biscarbamates reacted with a (Z)-2-(methylthio)allyl silyl ether to afford syn adducts in >94% selectivity.
  • M TAKAYANAGI, N UMAMORI, K TANINO, KUWAJIMA, I
    JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 115 (26) 12635 - 12636 0002-7863 1993/12 [Refereed][Not invited]
  • M TAKAHASHI, K TANINO, KUWAJIMA, I
    CHEMISTRY LETTERS (10) 1655 - 1658 0366-7022 1993/10 [Refereed][Not invited]
     
    N-Acylated 4-piperidone was prepared in good overall yield through an initial formation of the imine from the reaction of alpha'-aminomethylated enol silyl ether with an aldehyde followed by cyclization effected with an acid anhydride. The latter cyclization reaction seems to proceed preferentially through a boat-like transition state to give the piperidone having exo substituent.
  • H SHODA, T NAKAMURA, K TANINO, KUWAJIMA, I
    TETRAHEDRON LETTERS 34 (39) 6281 - 6284 0040-4039 1993/09 [Refereed][Not invited]
     
    Use of organoaluminum reagents induces ene-like reactions of enol silyl ethers with aldehydes, and enols having bulky silyl groups selectively afforded syn adducts.
  • S KAMEI, Y SAKAI, Y OHASHI, A ADACHI, K TANINO, KUWAJIMA, I
    ACTA CRYSTALLOGRAPHICA SECTION C-CRYSTAL STRUCTURE COMMUNICATIONS 49 1509 - 1511 0108-2701 1993/08 [Refereed][Not invited]
     
    The crystal structure of (1S,3S)-3-acetyl-5-methoxy-3-methylthio-1,2,3,4-tetrahydronaphthalene-1,8-diyl dibenzoate contains two independent molecules. These molecules have a similar conformation except for the dihedral angles between the aromatic ring and the benzoyloxy group linked to it, which differ by a relative rotation of -160-degrees. The absolute configurations of the two chiral centres C8 and C10 are established as S and S.
  • A ADACHI, K MASUYA, K TANINO, KUWAJIMA, I
    JOURNAL OF ORGANIC CHEMISTRY 58 (16) 4189 - 4190 0022-3263 1993/07 [Refereed][Not invited]
     
    A highly enantioselective synthesis of anthracycline precursors (1a and 10) was accomplished through a chirality-transfer ene reaction.
  • T NAKAMURA, K TANINO, KUWAJIMA, I
    TETRAHEDRON LETTERS 34 (3) 477 - 480 0040-4039 1993/01 [Refereed][Not invited]
     
    Under the chelation conditions the title compounds reacted with alpha-benzyloxyaldehyde to afford syn diol exclusively. Further, three contiguous diastercomeric centers were constructed with high stereoselectivity by using (E) or (Z)-crotyl silyl ether. This methodology was applied to the stereoselective synthesis of brassinolide side chain.
  • K TANINO, M TAKAHASHI, K MURAYAMA, KUWAJIMA, I
    JOURNAL OF ORGANIC CHEMISTRY 57 (26) 7009 - 7010 0022-3263 1992/12 [Refereed][Not invited]
     
    N-(Trimethylsilyl)formaldimine-AlCl3 complex 2b was generated by treating (trimethylsilyl)methyl azide with AlCl3. The reaction of 2b with various kinds of enol triisopropylsilyl ethers afforded alpha'-aminomethylated enol silyl ethers in good yields.
  • T NAKAMURA, K TANINO, KUWAJIMA, I
    CHEMISTRY LETTERS (8) 1425 - 1428 0366-7022 1992/08 [Refereed][Not invited]
     
    In the presence of Lewis acid 2-(alkylthio)crotyl silyl ethers(1) react with aldehydes to give anti or syn adducts with high selectivity, depending on the geometry of 1. Further, on using TiCl4. E-adducts are produced, whereas Z selectivity is observed in the other Lewis acid promoted reactions.
  • K TANINO, H SHODA, T NAKAMURA, KUWAJIMA, I
    TETRAHEDRON LETTERS 33 (10) 1337 - 1340 0040-4039 1992/03 [Refereed][Not invited]
     
    A highly enantio-selective ene reaction was developed on the bases of chirality transfer. Under the influence of Me2AlCl, the reactions of various aldehydes with (S)-3-(tert-butyldimethylsiloxy)-2-(ethylthio)-1-butene which was easily prepared from (S)-ethyl lactate afforded the optically active adducts in high ee.
  • K TANINO, T NAKAMURA, KUWAJIMA, I
    TETRAHEDRON LETTERS 31 (15) 2165 - 2168 0040-4039 1990 [Refereed][Not invited]
  • T MATSUDA, K TANINO, KUWAJIMA, I
    TETRAHEDRON LETTERS 30 (32) 4267 - 4270 0040-4039 1989 [Refereed][Not invited]
  • K TANINO, K SATO, KUWAJIMA, I
    TETRAHEDRON LETTERS 30 (47) 6551 - 6554 0040-4039 1989 [Refereed][Not invited]
  • K TANINO, T KATOH, KUWAJIMA, I
    TETRAHEDRON LETTERS 29 (15) 1815 - 1818 0040-4039 1988 [Refereed][Not invited]
  • T KATOH, K TANINO, KUWAJIMA, I
    TETRAHEDRON LETTERS 29 (15) 1819 - 1822 0040-4039 1988 [Refereed][Not invited]
  • K TANINO, Y HATANAKA, KUWAJIMA, I
    CHEMISTRY LETTERS (2) 385 - 388 0366-7022 1987 [Refereed][Not invited]

Books etc

  • 天然物全合成の最新動向
    シーエムシー出版 2009
  • 天然物化学 植物編
    アイピーシー 2007
  • 第5版実験化学講座 16有機化合物の合成IV
    丸善 2005

MISC

  • Takahashi Motomasa, Tomata Yoshihide, Tokura Hiroshi, Uehara Kento, Narabu Takashi, Miyashita Masaaki, Tanino Keiji  天然有機化合物討論会講演要旨集  (52)  139  -144  2010/09/01  [Not refereed][Not invited]
     
    Solanoeclepin A (1), isolated from a large quantity of potatoes as the most active hatching agent of potato cyst nematodes in 1986, possesses a unique heptacyclic structure containing all ring sizes from three to seven with various oxygen functional groups. The first asymmetric total synthesis of Solanoeclepin A was achieved on the basis of (1) the intramolucular Diels-Alder reaction of a 3-methoxyfuran derivative, and (2) an intramolecular cyclization reaction of an epoxy nitrile. Epoxy nitrile 6 was synthesized from optically active nitrile 7 through semi-pinacol rearrangement of epoxy alcohol 12 mediated by TMSOTf. Treatment of epoxy nitrile 6 with LDA followed by TBSCl and HMPA afforded the cyclization product 10 having a the tricyclo[5.2.1.0^<1.6>]decane skeleton in high yield. Elaboration of the cyclopropane side chain was effected by using the enantioselective cyclopropanation reaction reported by Charette. A methoxyfuran moiety and an enone side chain was introduced to the right-hand segment 22, and the product 26 was subjected to the crucial intramolecular Diels-Alder reaction promoted by Me_2AlCl. The product having the heptacyclic skeleton of Solanoeclepin A was obtained in 62% yield. Oxidation of the 7-membered ring and elaboration of other functional groups gave rise to synthetic Solanoeclepin A (total 52 steps, 0.11% overall yield).

Awards & Honors

  • 2013 The Chemical Society of Japan Award for Creative Work
     
    受賞者: 谷野 圭持
  • 2011 Nagoya Silver Medal
     
    受賞者: TANINO Keiji
  • 2007 The Society of Synthetic Organic Chemistry, Japan Mukaiyama Award
  • 2000 The Society of Synthetic Organic Chemistry, Japan Incentive Award in Synthetic Organic Chemistry

Research Grants & Projects

  • 文部科学省:科学研究費補助金(基盤研究(B))
    Date (from‐to) : 2018 -2020 
    Author : 谷野 圭持
  • 文部科学省:科学研究費補助金(新学術領域研究(研究領域提案型))
    Date (from‐to) : 2015 -2019 
    Author : 谷野 圭持
  • 文部科学省:科学研究費補助金(基盤研究(B))
    Date (from‐to) : 2015 -2017 
    Author : 谷野 圭持
  • 文部科学省:科学研究費補助金(基盤研究(B))
    Date (from‐to) : 2012 -2014 
    Author : 谷野 圭持
  • 文部科学省:科学研究費補助金(新学術領域研究(研究領域提案型))
    Date (from‐to) : 2009 -2012 
    Author : 谷野 圭持
     
    多官能性天然有機化合物の全合成においては,工程数の短縮が成功の鍵を握ることから、環骨格形成において複数の炭素-炭素結合を一挙に形成する反応集積化手法の開発を目指した。まず、単子菌類から単離されたセスキテルペンであるフランエーテルBを合成標的とし、シロキシアレンとアセチレンジコバルト錯体の[5+2]型付加環化反応を開発した。この効率的7員環構築法とエノールシリルエーテルの分子内アルキル化反応を組み合わせて、ヒドロアズレン骨格を構築した。次に、硝酸アンモニウムセリウムを用いてコバルト錯体部位の無水マレイン酸への変換と渡環エーテル部の形成を一挙に行なった。最後に、無水マレイン酸部を還元的にフラン環に変換し、フランエーテルBの全合成を達成した。次に、サンゴ類から抽出されるクラジエリンテルペノイドを合成標的とし、それらに含まれる11-オキサビシクロ[6.2.1]ウンデカン骨格をアセチレンジコバルト錯体とフランの[6+4]型付加環化反応により構築した。得られたコバルト錯体に酢酸中でヨウ素と酢酸銅(II)を作用させると、渡環酸素の転位を伴う特異なヨウ素化反応が進行し、11-オキサビシクロ[5.3.1]ウンデカン骨格を有するアリル酢酸エステルが生成することを見出した。光学分割を経て合成した光学活性エノンから、有機銅試薬の共役付加反応および分子内環化反応を経て6員環を構築した。共役付加によりイ...
  • 文部科学省:科学研究費補助金(基盤研究(B))
    Date (from‐to) : 2009 -2011 
    Author : 谷野 圭持
     
    ソラノエクレピンAの関連化合物であり、ダイズシストセンチュウ孵化促進物質であるグリシノエクレピンAについて、不斉全合成に成功した。本合成の特長は、1)独自に開発したシクロペンテンアヌレーション法によるビシクロ[4.3.0]ノナン骨格の立体選択的構築、2)ヒドロホウ素化反応・鈴木-宮浦カップリングによる側鎖の立体選択的導入、3)7-オキサビシクロ[2.2.0]ヘプタン骨格を有する橋頭位アニオンを用いるA環導入、にある。グリシノエクレピンAの全合成は既に3例が報告されているが、上記の方法論を開発することで従来法をしのぐ効率的な全合成が達成でき、Chemistry Letters誌に発表した論文はEditors Choiceに選定された。一方、前年度に明らかとなったソラノエクレピンAの全合成における問題点は、1)分子内Diels-Alder反応における面制御、2)混み合った環境にあるC19位水酸基の立体選択的還元、3)複数の酸素官能基の選択的変換、であった。これらの諸問題について、1)C19位水酸基の保護基と反応溶媒の検討、2)還元剤としてのDBALの採用、3)TMS基の特性を利用した水酸基の区別、の解決法を見出した結果、ソラノエクレピンAの世界初の全合成を達成した。本合成品を用いて、ジャガイモシストセンチュウの孵化活性試験を行ない、極めて低濃度の水溶液中で顕著な孵化促進活性を示す...
  • Ministry of Education, Culture, Sports, Science and Technology:Grants-in-Aid for Scientific Research(基盤研究(B))
    Date (from‐to) : 2007 -2009 
    Author : Masaaki MIYASHITA, 谷野 圭持, 南雲 紳史, Keiji TANINO, Shinji NAGUMO
     
    Recently, there have been discovered an extremely small quantity of natural products with novel chemical structures and distinctive biological properties which have drawn much attention inside and outside the country, particularly, in relation to development of a new type of medicines. This research mainly aimed at chemical synthesis of the zoanthamine alkaloids that have exhibited potent biological and pharmacological activities. As a result, we achieved the first chemical syntheses of zoanthamine with powerful analgesic effects, and zoanthenol with potent antiplatelet activities on human ...
  • 文部科学省:科学研究費補助金(特定領域研究)
    Date (from‐to) : 2004 -2008 
    Author : 福山 透, 小林 資正, 佐々木 誠, 谷野 圭持, 菅 敏幸
     
    平成20年6月に、取りまとめの公開シンポジウムをタワーホール船堀(東京)にて実施した。このとき代表的な研究成果を中心に公開し、成果を社会に対して発信した。これらの研究成果は、生命現象の化学的解明に飛躍的な進展や新戦略による創薬にも直結するため、製薬に代表される産業界においても有用であり、公開シンポジウムでは企業の研究者も幅広く参加した。また、本特定領域研究では、各研究項目の計画研究班員と公募班員の間での緊密な共同研究体制を構築することを重要課題として掲げた。これまで、公開シンポジウムやHPにより研究者の相互の理解を深め、有機的連携と緊密な共同研究体制を構築した。現在までに、30組以上の領域内共同研究が進行中であり、成果があがりつつある。また、最終報告も平成21年3月に作成した。この最終報告書にはおのずと解決された問題と、さらに解決されなかった問題(既存の学術誌等には投稿できない)が例示されることとなるため、この方面の研究者にとって研究課題が容易に見つけ出せるバイブル的な存在になるように留意し整理した。また、班員、研究協力者、班友の業績を中心としたテキスト「天然物の全合成 : 2001〜2008」の編纂を行った。現在最終校正の段階にあり、平成21年中に発売可能な状態にある。本特定領域ではすでに50を超える生理活性天然物(生体機能分子)の全合成を達成している。それらを網羅する本書...
  • 文部科学省:科学研究費補助金(特定領域研究)
    Date (from‐to) : 2004 -2007 
    Author : 谷野 圭持, 宮下 正昭, 吉村 文彦
     
    昨年度は、独自のシクロペンテンアヌレーション法および橋頭位アニオンを用いるA環部導入法を駆使し、ダイズシスト線虫孵化促進物質グリシノエクレピンAの不斉全合成を達成した。今年度はまず、この知見をさらに発展させて天然物グリシノエクレピンBの不斉全合成を目指した。本化合物はグリシノエクレピンAの類縁体であるが、D環上の側鎖にγ-ヒドロキシ-α,β-不飽和カルボン酸部位を有する点が異なる。この部位の立体選択的構築法を検討した結果、光学活性配位子を用いる不斉野崎-檜山-岸カップリング反応を用いることにより、世界初の不斉全合成を達成することができた。一方、昨年度から着手した高次構造天然物アザジラクチンの全合成研究においては、高度に縮環したEFG環部の効率的な合成法を検討した。その結果、Nazarov環化反応によりE環を、分子内ェーテル環化によりF環を、メチルチオ基を水銀塩で活性化する分子内グリコシル化反応によりG環を各々構築し、モデル化合物の効率的合成に成功した。今後は、この知見を既に確立したC8位四級不斉炭素の立体選択的構築法と組み合わせることで、アザジラクチンの全合成が達成する計画である。さらに、海洋産天然物スクレロフィチンAの全合成研究において、以下の画期的な進展があった。従来は、[6+4]型付加環化反応により構築した11-オキサビシクロ[6.2.1]ウンデカン骨格が、脱コバルト錯...
  • Ministry of Education, Culture, Sports, Science and Technology:Grants-in-Aid for Scientific Research(基盤研究(B))
    Date (from‐to) : 2004 -2005 
    Author : Masaaki MIYASHITA, 谷野 圭持
     
    (1)Aymmetric Total Syntheses of Norzoanthamine and ZoanthamineNorzoanthamine can suppress the loss of bone weight and strength in ovariectomized mice and has been considered a promising candidate for an antiosteoporotic drug. On the other hand, zoanthamine has exhibited potent inhibitory activity toward phorbol myristate-induced inflammation in addition to powerful analgesic effects. The distinctive biological properties and novel chemical structures of this family of alkaloids make them extremely attractive targets for chemical synthesis. However, the chemical synthesis of the zoanthamine ...
  • Ministry of Education, Culture, Sports, Science and Technology:Grants-in-Aid for Scientific Research(基盤研究(B))
    Date (from‐to) : 2002 -2004 
    Author : Keiji TANINO
     
    (1)New aspects of [5+2] cycloaddition reactionsIn order to explore the scope and limitations of the [5+2] cycloaddition reaction using the five-carbon unit having an acetylene dicobalt complex moiety and an enol silyl ether moiety, the reactions with various electron rich olefins as well as aromatic compounds were examined. Although aromatic compounds including anisols and aniline derivatives gave no good results, the reaction with a siloxyallene derivative was found to give the desired seven-membered cycloadduct in good yield.(2)Development of the higher-order cycloaddition reactionsA new ...
  • Ministry of Education, Culture, Sports, Science and Technology:Grants-in-Aid for Scientific Research(基盤研究(A))
    Date (from‐to) : 2000 -2002 
    Author : Masaaki MIYASHITA, 谷野 圭持
     
    Development of highly stereoselective synthetic methodologies for acyclic organic molecules having contiguous asymmetric centers is one of the important research projects in modern synthetic organic chemistry in context with the chiral synthesis of biologically and medicinally important compounds. This research project was carried out aiming at the development of highly stereoselective synthetic methodologies for acyclic organic molecules having contiguous asymmetric centers using stereospecific substitution reactions of epoxides as synthetic strategy .when this grant was provided.(1) The C...
  • 文部科学省:科学研究費補助金(奨励研究(A))
    Date (from‐to) : 1998 -1999 
    Author : 谷野 圭持
     
    筆者は昨年度までに、コバルトアセチレン錯体部位を有するtrans-デカリノール誘導体の分子内環化反応およびエポキシアルコールの炭素骨格転位反応を経て新規なインゲナン誘導体を合成することに成功した。この化合物はインゲノールと等しいCD環部を有するのみならず、A環上の1位およびB環上の6位に各々酸素官能基を有する重要中間体である。今年度は、このインゲナン誘導体からインゲノールへの変換を実現するべく、まずA環の官能基化を検討した。すなわち、1位水酸基をケトンへと酸化した後、2位へのexo-メチレン基の導入および水素添加を経て2-メチル体を合成した。さらに、1位ケト基を還元して得たアルコールを脱水反応によりC(1)-C(2)オレフィンとした後、クロム酸を用いたアリル位の酸化反応により3位にケト基を導入した。最後に、DIBALを用いて3位ケト基を立体選択的に還元し、インゲノールのA環に存在するすべての官能基の導入を達成した。一方、これと並行してB環の官能基化についても以下の検討を行った。すなわち、6位水酸基をケトンへと酸化した後、塩基で処理して4位のメトキシ基をβ-脱離させ、共役エノンを得た。このものに塩基性過酸化水素を作用させて立体選択的にC(4)-C(5)エポキシドとした後、Peterson反応により6位ケト基をケテンジチオアセタールへと変換した。最後に、塩化銅で処理してエポキシド...
  • 文部科学省:科学研究費補助金(重点領域研究, 特定領域研究(A))
    Date (from‐to) : 1997 -1999 
    Author : 吉田 潤一, 堀口 良昭, 澤村 正也, 岩澤 伸治, 大嶋 幸一郎, 神戸 宣明, 碇屋 隆雄, 谷野 圭持
     
    本研究では新化学現象・新反応の発見と開拓のために、反応の分子環境としての反応場、反応剤、反応媒体、反応手法などを反応メディアという観点から研究を行ってきた。とくに、電子移動反応場、高分子反応場、結晶反応場、ラジカル反応場、金属錯体反応場、特異条件反応場とそれらの境界領域について重点的に検討を行い、新現象・新反応の発見を目指して検討を行ってきた。その結果、多くの特筆すべき成果を得ることができた。以下に示す。電子移動反応場においては、活性種の生成条件を高度に制御することにより、生成した活性種を蓄え、それを結合生成反応に用いるというカチオンプール法を開拓し、炭素-炭素結合生成反応の新しい方法論を明らかにした。さらに、電解反応場と固体マトリックス反応場の組み合わせにより、高効率・高選択的な分子変換法を明らかにした。また、有機金属反応場、ラジカル反応場、カチオン反応場においては、新活性種や機能性反応場反応の構築などにおいて顕著な成果を上げることができた。媒体の研究においても注目すべき成果が得られた。すなわち、水中におけるラジカル反応において、従来の有機溶媒中の反応にみられない興味深い応性の変化や選択性の変化が観測されることを明らかにした。また、水中におけるイオン反応の促進効果を利用し、ラジカル反応とイオン反応を組み合わせる新しい反応系の開発をも明らかにした。さらに、超臨界流体における金...
  • Ministry of Education, Culture, Sports, Science and Technology:Grants-in-Aid for Scientific Research(基盤研究(B))
    Date (from‐to) : 1996 -1997 
    Author : Isao KUWAJIMA, 谷野 圭持
     
    The following synthetically useful methodologies have been developed by this research project.(1) The substrates such as 3- (alkylthio) -2- (siloxy) - and 3- (alkylthio) -2- (silylmethyl) allyl acetates have been shown as useful three carbon units for [3 + 2] cylopentanone and methylene cyclopentane annulation in the reactions with electron-rich olefins. It has also been proposed the high observed regioselectivity is due to thermodynamic control of this reaction, and excellent stereoselectivity observed in the reaction with vinylsulfides may be due to remarkable effect of sulfur having a la...
  • Development of Selective C-C bond Farming ReactionsTotal Synthesis of Natural Products
    Date (from‐to) : 1997
  • 文部科学省:科学研究費補助金(奨励研究(A))
    Date (from‐to) : 1995 -1995 
    Author : 谷野 圭持
     
    まず、2-(メチルチオ)クロチルシリルエーテルと芳香族鎖状イミンとのエン反応について検討を行った結果、窒素上にアルコキシカルボニル基を導入することでイミンの反応性が著しく向上し、良好な収率で目的とする付加体が得られることを見出した。本反応のジアステレオ選択性は高く、エン基質のZ体はsyn体を、またE体はanti体をそれぞれ選択的に与えた。一方、対応する脂肪族鎖状イミンは合成困難であったが、1,1-ビスカルバマートを等価体として用いることで、高立体選択的にエン反応が進行することを明らかにした。次に、環状イミンとの反応について検討を行い、5-アシロキシピロリドン誘導体をイミン等価体として用いることでピロリジン環上へのジアステレオ選択的な側鎖導入を実現した。さらに、本反応の不斉合成への応用を試み、光学活性な1-フェネチルアミンから誘導される出発原料を用いればジアステレオ面選択的付加が起こることを明らかにした。以上の反応によって得られるエン付加体は、アシル基で保護されたアミノ基およびエノールシリルエーテル部位を合わせ持つことから、含窒素複素環の前駆体として有用であることを示した。すなわち、付加体を酸で処理するとエノールシリルエーテル部位の加水分解および環化が進行し、ピロリジノール誘導体を与えるが、このもののエステル誘導体にルイス酸共存下、種々の求核試剤を作用させることにより、環骨格上...

Educational Activities

Teaching Experience

  • Biochemistry A (IV)
    開講年度 : 2018
    課程区分 : 修士課程
    開講学部 : 総合化学院
    キーワード : カルボカチオン、ルイス酸、エノールシリルエーテル、アリルシラン、求電子付加反応、カルボラジカル、ラジカル還元反応、ラジカル付加反応、ラジカル環化反応
  • Inter-Graduate School Classes(General Subject):Natural and Applied Sciences
    開講年度 : 2018
    課程区分 : 修士課程
    開講学部 : 大学院共通科目
    キーワード : Biochemistry, Organic chemistry, Biosynthesis, Computational chemistry.
  • Advanced Chemistry
    開講年度 : 2018
    課程区分 : 修士課程
    開講学部 : 総合化学院
    キーワード : Biochemistry, Organic chemistry, Biosynthesis, Computational chemistry.
  • Modern Trends in Physical and Material Chemistry II
    開講年度 : 2018
    課程区分 : 修士課程
    開講学部 : 工学院
    キーワード : 有機構造化学,高分子機能科学,有機金属化学,有機物性化学,遺伝情報制御化学,疾病制御化学,有機合成化学,生物物理化学,生合成工学,生命システム工学,生物計測化学,機能性高分子,動物細胞培養工学
  • Modern Trends in Physical and Material Chemistry Ⅰ
    開講年度 : 2018
    課程区分 : 修士課程
    開講学部 : 工学院
    キーワード : 先端物理化学,物質変換化学,光化学,分子理論化学,化学エネルギー変換,分離プロセス工学,プロセス工学,触媒設計,機能解析化学,ナノフォトニクス材料,無機固体化学、ナノ物質化学,界面電子化学,無機物性化学,電子材料化学,機能固体化学,応用材料化学
  • Inter-Graduate School Classes(General Subject):Natural and Applied Sciences
    開講年度 : 2018
    課程区分 : 修士課程
    開講学部 : 大学院共通科目
    キーワード : 基礎有機化学、構造有機化学、反応有機化学、有機金属化学、有機合成化学、高分子化学
  • Special Lecture on Organic Chemistry
    開講年度 : 2018
    課程区分 : 修士課程
    開講学部 : 総合化学院
    キーワード : 基礎有機化学、構造有機化学、反応有機化学、有機金属化学、有機合成化学、高分子化学
  • Modern Trends in Physical and Material Chemistry II
    開講年度 : 2018
    課程区分 : 博士後期課程
    開講学部 : 工学院
    キーワード : 有機合成化学,有機金属化学,有機構造化学,生物有機化学,高分子合成化学,化学生物学,生物化学,分子生物学,生物物理化学,再生医療工学,生体触媒学,生物無機化学,生物計測化学,遺伝情報制御化学,疾病制御化学
  • Modern Trends in Physical and Material Chemistry Ⅰ
    開講年度 : 2018
    課程区分 : 博士後期課程
    開講学部 : 工学院
    キーワード : 先端物理化学,分子理論化学,集合機能化学,物質変換化学,光化学,材料製造工学,プロセス工学,分離生成工学,触媒材料設計,触媒反応設計,化学エネルギー変換,固体物性化学,機能解析化学,先端無機化学,ナノ物質化学,分子組織化学,固体化学,ナノセラミックス,界面電子化学,無機物性化学,無機プロセシング科学,電子材料化学,セラミック材科学,応用材料化学
  • Modern Trends in Chemical Sciences and Engineering II
    開講年度 : 2018
    課程区分 : 博士後期課程
    開講学部 : 総合化学院
    キーワード : Biochemistry, Organic chemistry, Biosynthesis, Computational chemistry.
  • The World of Science and Technology
    開講年度 : 2018
    課程区分 : 学士課程
    開講学部 : 全学教育
    キーワード : 無機物質、有機物質、生体物質、医薬品、環境問題
  • Organic Chemistry Ⅱ
    開講年度 : 2018
    課程区分 : 学士課程
    開講学部 : 理学部
    キーワード : ラジカル、芳香族、求電子置換反応、カルボニル化合物、求核付加反応


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