Papers - Ogura, Akihiro

Enantioselective Total Synthesis of (-)-Misramine

Keisuke Yoshida, Yuta Fujino, Yusei Takamatsu, Kohei Matsui, Akihiro Ogura, Yuri Fukami, Shinji Kitagaki, Ken Ichi Takao

Organic Letters (American Chemical Society ({ACS}))  20 ( 16 ) 5044 - 5047 2018.08

Research paper (scientific journal), Joint Work, Accepted,  ISSN  15237060

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© 2018 American Chemical Society. The enantioselective total synthesis of an unusual pentacyclic proaporphine alkaloid, (-)-misramine, was achieved. The synthetic strategy relied on an enantioselective intramolecular Friedel-Crafts-type 1,4-addition using an asymmetric organocatalyst to construct a spiroindane skeleton containing an all-carbon quaternary stereocenter and a double reductive amination of the keto-aldehyde to form a piperidine ring toward the end of the synthesis. This work is the first example of asymmetric synthesis of a proaporphine alkaloid.

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Total Synthesis of Clavilactones

Ken-ichi Takao, Kento Mori, Kenya Kasuga, Ryuki Nanamiya, Ayumi Namba, Yuuki Fukushima, Ryuichi Nemoto, Takuma Mogi, Hiroyuki Yasui, Akihiro Ogura, Keisuke Yoshida, Kin-ichi Tadano

JOURNAL OF ORGANIC CHEMISTRY (American Chemical Society ({ACS}))  83 ( 13 ) 7060 - 7075 2018.01

Research paper (scientific journal), Joint Work, Accepted,  ISSN  00223263

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A viable strategy for screening the effects of glycan heterogeneity on target organ adhesion and biodistribution in live mice

Akihiro Ogura, Sayaka Urano, Tsuyoshi Tahara, Satoshi Nozaki, Regina Sibgatullina, Kenward Vong, Takehiro Suzuki, Naoshi Dohmae, Almira Kurbangalieva, Yasuyoshi Watanabe, Katsunori Tanaka

Chemical Communications (Royal Society of Chemistry ({RSC}))  54 ( 63 ) 8693 - 8696 2018

Research paper (scientific journal), Joint Work, Lead author, Accepted,  ISSN  13597345

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Synthesis and evaluation of biological activities of vibsanin A analogs

Wataru Matsuki, So Miyazaki, Keisuke Yoshida, Akihiro Ogura, Yukiko Sasazawa, Ien-ichi Takao, Siro Simizu

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS (PERGAMON-ELSEVIER SCIENCE LTD)  27 ( 19 ) 4536 - 4539 2017.08

Research paper (scientific journal), Joint Work, Accepted,  ISSN  0960-894X

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Vibsanin A is an 11-membered vibsane diterpenoid and is reported to induce myeloid cell differentiation via activation of protein kinase C (PKC) without tumor-promoting activity. Therefore, vibsanin A is thought to be an attractive compound for acute myeloid leukemia (AML) therapy. In this study, we synthesized vibsanin A analogs and compared the activity of these compounds for PKC activation and myeloid cell differentiation. We found that the hydroxymethyl group in vibsanin A is an important substituent to induce differentiation of AML cells. Collectively, our results showed the biochemical features of vibsanin A and provided new insights into the development of new antileukemic drugs. (C) 2017 Elsevier Ltd. All rights reserved.

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Total Synthesis and Structural Revision of ClavilactoneD

Takao, Ken-ichi, Nemoto, Ryuichi, Mori, Kento, Namba, Ayumi, Yoshida, Keisuke, Ogura, Akihiro

CHEMISTRY-A EUROPEAN JOURNAL (WILEY-V C H VERLAG GMBH)  23 ( 16 ) 3828 - 3831 2017.03

Research paper (scientific journal), Joint Work, Last author, Accepted,  ISSN  0947-6539

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A structural revision of clavilactoneD, a potent inhibitor of protein tyrosine kinases, was achieved by total syntheses of two newly proposed structures. The syntheses relied on ring-opening/ring-closing metathesis, which transformed a cyclobutenecarboxylate into a -butenolide. The syntheses confirmed that the correct structure of clavilactoneD has an amino group at C-3 instead of a hydroxy group at C-2 in the originally proposed structure.

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In Vivo Gold Complex Catalysis within Live Mice

Kazuki Tsubokura, Kenward K. H. Vong, Ambara R. Pradipta, Akihiro Ogura, Sayaka Urano, Tsuyoshi Tahara, Satoshi Nozaki, Hirotaka Onoe, Yoichi Nakao, Regina Sibgatullina, Almira Kurbangalieva, Yasuyoshi Watanabe, Katsunori Tanaka

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION (WILEY-V C H VERLAG GMBH)  56 ( 13 ) 3579 - 3584 2017.03

Research paper (scientific journal), Joint Work, Accepted,  ISSN  1433-7851

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Metal complex catalysis within biological systems is largely limited to cell and bacterial systems. In this work, a glycoalbumin-Au-III complex was designed and developed that enables organ-specific, localized propargyl ester amidation with nearby proteins within live mice. The targeted reactivity can be imaged through the use of Cy7.5- and TAMRA-linked propargyl ester based fluorescent probes. This targeting system could enable the exploitation of other metal catalysis strategies for biomedical and clinical applications.

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Sequential Double "Clicks" toward Structurally Well-Defined Heterogeneous N-Glycoclusters: The Importance of Cluster Heterogeneity on Pattern Recognition In Vivo

Liliya Latypova, Regina Sibgatullina, Akihiro Ogura, Katsumasa Fujiki, Alsu Khabibrakhmanova, Tsuyoshi Tahara, Satoshi Nozaki, Sayaka Urano, Kazuki Tsubokura, Hirotaka Onoe, Yasuyoshi Watanabe, Almira Kurbangalieva, Katsunori Tanaka

ADVANCED SCIENCE (WILEY)  4 ( 2 ) 1600394 - 1600394 2017.02

Research paper (scientific journal), Joint Work, Accepted,  ISSN  2198-3844

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Exploring the glycan interaction in vivo: Future prospects of neo-glycoproteins for diagnostics

Akihiro Ogura, Almira Kurbangalieva, Katsunori Tanaka

GLYCOBIOLOGY (OXFORD UNIV PRESS INC)  26 ( 8 ) 804 - 812 2016.08

Accepted,  ISSN  0959-6658

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Herein the biodistributions and in vivo kinetics of chemically prepared neoglycoproteins are reviewed. Chemical methods can be used to conjugate various mono- and oligosaccharides onto a protein surface. The kinetics and organ-specific accumulation profiles of these glycoconjugates, which are introduced through intravenous injections, have been analyzed using conventional dissection studies as well as noninvasive methods such as single photon emission computed tomography, positron emission tomography and fluorescence imaging. These studies suggest that glycan-dependent protein distribution kinetics may be useful for pharmacological and diagnostic applications.

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Glycan multivalency effects toward albumin enable N-glycan-dependent tumor targeting

Ogura, Akihiro, Tahara, Tsuyoshi, Nozaki, Satoshi, Onoe, Hirotaka, Kurbangalieva, Almira, Watanabe, Yasuyoshi, Tanaka, Katsunori

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS (PERGAMON-ELSEVIER SCIENCE LTD)  26 ( 9 ) 2251 - 2254 2016.05

Research paper (scientific journal), Joint Work, Lead author, Accepted,  ISSN  0960-894X

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Multivalent interactions play an essential role in molecular recognition in living systems. These effects were employed to target tumor cells using albumin clusters bearing similar to 10 molecules of asparagine-linked glycans (N-glycans). Noninvasive near-infrared fluorescence imaging clearly revealed A431 tumors implanted in BALB/cA-nu/nu mice after 1 h in an N-glycan structure-dependent manner, thereby demonstrating the efficient use of glycan multivalency effects for tumor targeting in vivo. (C) 2016 Elsevier Ltd. All rights reserved.

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Visualizing Trimming Dependence of Biodistribution and Kinetics with Homo- and Heterogeneous N-Glycoclusters on Fluorescent Albumin

Ogura, Akihiro, Tahara, Tsuyoshi, Nozaki, Satoshi, Morimoto, Koji, Kizuka, Yasuhiko, Kitazume, Shinobu, Hara, Mitsuko, Kojima, Soichi, Onoe, Hirotaka, Kurbangalieva, Almira, Taniguchi, Naoyuki, Watanabe, Yasuyoshi, Tanaka, Katsunori

SCIENTIFIC REPORTS (NATURE PUBLISHING GROUP)  6   273 - 279 2016.02

Research paper (scientific journal), Joint Work, Lead author, Accepted,  ISSN  2045-2322

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A series of N-glycans, each sequentially trimmed from biantennary sialoglycans, were homo-or heterogeneously clustered efficiently on fluorescent albumin using a method that combined strain-promoted alkyne-azide cyclization and 6p-azaelectrocyclization. Noninvasive in vivo kinetics and dissection analysis revealed, for the first time, a glycan-dependent shift from urinary to gall bladder excretion mediated by sequential trimming of non-reducing end sialic acids. N-glycoalbumins that were trimmed further, in particular, GlcNAc-and hybrid biantennary-terminated congeners, were selectively taken up by sinusoidal endothelial and stellate cells in the liver, which are critical for diagnosis and treatment of liver fibrillation. Our glycocluster strategy can not only reveal the previously unexplored extracellular functions of N-glycan trimming, but will be classified as the newly emerging glycoprobes for diagnostic and therapeutic applications.

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In vivo imaging of advanced glycation end products (AGEs) of albumin: first observations of significantly reduced clearance and liver deposition properties in mice

Tsutsui, Ayumi, Ogura, Akihiro, Tahara, Tsuyoshi, Nozaki, Satoshi, Urano, Sayaka, Hara, Mitsuko, Kojima, Soichi, Kurbangalieva, Almira, Onoe, Hirotaka, Watanabe, Yasuyoshi, Taniguchi, Naoyuki, Tanaka, Katsunori

ORGANIC & BIOMOLECULAR CHEMISTRY (ROYAL SOC CHEMISTRY)  14 ( 24 ) 5755 - 5760 2016

Research paper (scientific journal), Joint Work, Lead author, Accepted,  ISSN  1477-0520

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Advanced glycation end products (AGEs) are associated with various diseases, especially during aging and the development of diabetes and uremia. To better understand these biological processes, investigation of the in vivo kinetics of AGEs, i.e., analysis of trafficking and clearance properties, was carried out by molecular imaging. Following the preparation of Cy7.5-labeled AGE-albumin and intravenous injection in BALB/cA-nu/nu mice, noninvasive fluorescence kinetics analysis was performed. In vivo imaging and fluorescence microscopy analysis revealed that non-enzymatic AGEs were smoothly captured by scavenger cells in the liver, i.e., Kupffer and other sinusoidal cells, but were unable to be properly cleared from the body. Overall, these results highlight an important link between AGEs and various disorders associated with them, which may serve as a platform for future research to better understand the processes and mechanisms of these disorders.

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Azaelectrocyclization on cell surface: convenient and general approach to chemical biology research

Ogura, Akihiro, Tanaka, Katsunori

TETRAHEDRON (PERGAMON-ELSEVIER SCIENCE LTD)  71 ( 26-27 ) 4518 - 4521 2015.07

Research paper (scientific journal), Joint Work, Lead author, Accepted,  ISSN  0040-4020

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Convenient and general method for live cell surface labeling was established. Azide-containing fluorescences were initially conjugated with the unsaturated ester aldehyde containing the dibenzocyclooctyne (DIBO), by the strain-promoted click reaction. The resulting probes were then treated with the live cells in one-pot process, efficiently labeling the surface lysines by azaelectrocyclization under the mild conditions. (C) 2015 Elsevier Ltd. All rights reserved.

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Microfluidic Mixing of Polyamine with Acrolein Enables the Detection of the [4+4] Polymerization of Intermediary Unsaturated Imines: The Properties of a Cytotoxic 1,5-Diazacyclooctane Hydrogel

Pradipta, Ambara R., Tsutsui, Ayumi, Ogura, Akihiro, Hanashima, Shinya, Yamaguchi, Yoshiki, Kurbangalieva, Almira, Tanaka, Katsunori

SYNLETT (GEORG THIEME VERLAG KG)  25 ( 17 ) 2442 - 2446 2014.10

Research paper (scientific journal), Joint Work, Accepted,  ISSN  0936-5214

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The [4+4] polymerization of an unsaturated imine, generated from the condensation of a polyamine and excess acrolein, was investigated. The polyamine was added by micropipet to acrolein, immediately yielding a mixture of the immiscible polymeric material. Microfluidic mixing was used to gradually form the soluble diazacyclooctane polymers. The polymerization reaction ultimately gave an insoluble cationic hydrogel that adhered strongly to anionic compounds on cell surfaces, including sialoglycan, and displayed a high cytotoxicity.

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In vivo kinetics and biodistribution analysis of neoglycoproteins: effects of chemically introduced glycans on proteins

Akihiro Ogura, Almira Kurbangalieva, Katsunori Tanaka

GLYCOCONJUGATE JOURNAL (SPRINGER)  31 ( 4 ) 273 - 279 2014.05

Accepted,  ISSN  0282-0080

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Biodistribution and in vivo kinetics analysis of chemically prepared neoglycoproteins are reviewed. Various mono- and oligosaccharides were conjugated onto the protein surface by use of chemical methods. Their kinetic and organ-specific accumulation have extensively been studied after intravenous injection and analyzed by conventional dissection studies, as well as noninvasive methods, such as SPECT, PET, or fluorescence imaging. These studies clearly show the glycan-structure dependency on protein kinetics, which will provide promising possibilities for pharmacological and diagnostic applications.

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Total Synthesis of (-)-Anisatin

Ogura, Akihiro, Yamada, Kohei, Yokoshima, Satoshi, Fukuyama, Tohru

ORGANIC LETTERS (AMER CHEMICAL SOC)  14 ( 6 ) 1632 - 1635 2012.03

Research paper (scientific journal), Joint Work, Lead author, Accepted,  ISSN  1523-7060

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A novel synthetic route to (-)-anisatin has been developed. Our synthesis features a rhodium-catalyzed 1,4-addition of an arylboronic acid, an intramolecular Diels Alder reaction of an ortho-quinone monoketal, a stereoselective [2,3]-Wittig rearrangement, and construction of the oxabicyclo [3.3.1] skeleton via cleavage of an epoxide by a primary amide.

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Total Synthesis of Anisatin

Yamada Kohei, Ogura Akihiro, Yokoshima Satoshi, Fukuyama Tohru

Symposium on the Chemistry of Natural Products, symposium papers (Symposium on the chemistry of natural products)   ( 52 ) 127 - 132 2010.09

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Anisatin (1), isolated as a toxic component of Japanese Star Anise, is a sesquiterpene characterized by eight contifuous stereogenic centers, oxabicyclo[3.3.1] skeleton, and spiro β-lactone. Its challenging structure, as well as the stron bioactivity as a GABA antagonist, has attracted many synthetic organic chemists. Despite numerous synthetic studies reported to date, only one total synthesis has been achieved. Inspired by its challenging structure, we also initiated our own research program directed toward a total synthesis of thi sinteresting molecule. Our synthesis commenced with the synthesis of phenol 7 from the known mono-protected catechol in seven steps. Oxidation of 7 with iodobenzene diacetate yielded orthoquinone monoketal, which upon heating underwent intramolecular Diels-Alder reaction to privide tetracyclic compound 14. After a three-step conversion, the resulting ether 16 was treated with methyllithium in the presence of HMPA, which induced diastereoselective [2,3]-sigmatropic rearrangement. Thus, the quaternary carbon was constructed with complete stereoselectivity. Selective cleavage of the trisubstituted souble bond of 17 by careful ozonolysis, followed by treatment with potassium carbonate provided 19. After a six-step conversion, iodide 22 was subjected to halogen-lithium exchange, which caused intramolecular addition to ketone to provide bicylco[4.3.0] skeleton. The enol ether moiety of 23 was oxidized to α-hydroxylactone, and the allyl alcohol moiety was converted to epoxide to provide 27. Upon ammonolysis of the lactone moiety, intramolecular S_N2 reaction to epoxide took place to give, after acid treatment, the desired lactone 29. Removal of the primary hydroxy group and protection of the resultin g tertiary alcohol afforded 31. The vinyl group of 31 was converted to carboxylic acid, followed by deprotection of the primary hydroxy group. Crucial lactonization was performed with MNBA to yield desired β-lactone successfully. A three-step sequence involving dihydroxylation of the trisubstituted olefin afforded 1. Having achieved total synthesis of racemic anisatin, we turned our attention to asymmetric synthesis. Phenol 35 and epoxyalcohol 36 were condensed by Mitsunobu reaction. Resulting ether 37 was subjected to halogen-lithium exchange. Bis(diethylaluminium)sulfate facilitated intramolecular S_N2 reaction to afford 38. HPLC analysis revealed that 38 was enantiomerically pure. Further synthetic studies toward asymmetric synthesis are currently under way.

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