Papers - Ogura, Akihiro

Synthetic Studies of Polycyclic Polyprenylated Acylphloroglucinols: Asymmetric Construction of a Cyclohexanone Moiety

Nanataki, S; Aoki, D; Onozawa, H; Akiya, T; Okuyama, G; Abo, K; Yoshida, K; Ogura, A; Takao, KI

Synlett 36 ( 10 ) 1375 - 1378 2025.03

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

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As a common intermediate for polycyclic polyprenylated acylphloroglucinols (PPAPs), we successfully synthesized a cyclohexanone moiety that contains two adjacent stereocenters, one of which is a quaternary carbon. Our synthetic strategy relied on an asymmetric Claisen rearrangement using Oppolzer's camphorsultam and a regioselective Dieckmann condensation.

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Synthesis of Tetrahydro‐β‐carbolines via Cascade Sigmatropic Rearrangements

Oka, D; Ohtsuka, T; Takao, KI; Ogura, A

Advanced Synthesis & Catalysis 367 ( 3 )  2024.11

Research paper (scientific journal), Joint Work, Accepted,  ISSN  1615-4150

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We have developed a synthesis for tetrahydro-β-carbolines involving cascade sigmatropic rearrangements. The substrates were conveniently prepared from parent anilines via a [2,3]-sigmatropic rearrangement and cyanomethylation. Silver-mediated decyanation afforded the corresponding iminium cation, which underwent a cascade consisting of an aza-Cope rearrangement, an aza-oxa-Cope rearrangement, an aromatization, and a Pictet-Spengler reaction, and tetrahydro-β-carbolines were obtained as the single product. The reaction involved seven bond scissions and four bond formations and was triggered by a single reagent.

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Antiproliferative activities through accelerating autophagic flux by basidalin and its analogs in human cancer cells.

Matagawa T, Sasazawa Y, Agui K, Fujimaki M, Kawano S, Ogura A, Takao KI, Igarashi M, Simizu S

Bioorganic & medicinal chemistry letters (Bioorganic and Medicinal Chemistry Letters)  104   129713 - 129713 2024.03

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

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Basidalin, isolated from the basidiomycete Leucoagaricus naucina, has previously demonstrated antibacterial and antitumor properties against murine cancer cells in vivo, but its effects on human cancer cells remain unknown. In this study, we found that basidalin possesses antiproliferative activity against human cancer cell lines. To elucidate the antiproliferative mechanism of basidalin, we focused on autophagy. Treatment with basidalin led to an increase in LC3-II expression level, and accelerated autophagic flux through an mTOR-independent pathway. Moreover, according to the structure-activity relationship analysis-including newly synthesized basidalin analogs-the formyl group, not the amino group, contributes to the antiproliferative activities of basidalin against human cancer cells. Additionally, the antiproliferative activity of basidalin analogs was strongly correlated with autophagy-inducing activity, indicating that basidalin exhibits antiproliferative activity through autophagy induction. These data suggest that basidalin, characterized by its ability to upregulate autophagic flux, emerges as a novel anticancer drug.

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Synthesis of Indoles via Sigmatropic Rearrangements and Olefin Isomerization

Tomoki Uchida, Ryosuke Saito, Ken‐ichi Takao, Akihiro Ogura

Advanced Synthesis & Catalysis (Advanced Synthesis and Catalysis)  366 ( 3 ) 465 - 472 2024.02

Research paper (scientific journal), Joint Work, Accepted,  ISSN  1615-4150

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Indoles are important heterocycles in pharmaceuticals and agrochemicals, and their atom-economical synthesis is needed. Herein, we describe the synthesis of indoles using sigmatropic rearrangements. The N-allylaniline was oxidized by environmentally benign hydrogen peroxide, and spontaneous [2,3]-Meisenheimer rearrangement gave N-allyloxyaniline. Subsequent treatment with a ruthenium catalyst afforded N-vinyloxyaniline, which underwent [3,3]-sigmatropic rearrangement to give indoles, expelling water as the only byproduct. The whole sequence is free of quantitative salt byproducts, thereby avoiding aqueous work up and cutting off the inorganic waste.

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Open system massive synthesis of narrow-band blue and green fluorescent graphene quantum dots and their application in water sensing

Ochi, Y; Otani, A; Katakami, R; Ogura, A; Takao, K; Iso, Y; Isobe, T

Journal of Materials Chemistry C (Journal of Materials Chemistry C)  12 ( 18 ) 6548 - 6558 2024

Research paper (scientific journal), Joint Work, Accepted,  ISSN  2050-7526

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Graphene quantum dots (GQDs) are environmentally friendly fluorescent carbon-based nanomaterials. However, there is no report on the massive synthesis of GQDs with narrow-band fluorescence and a high photoluminescence quantum yield (PLQY) using a simple liquid-phase method under atmospheric conditions. In this study, GQDs were successfully synthesized in ∼100% product yield by heating phloroglucinol (PG) with Na3PO4·12H2O in 1,2-pentanediol at 180 °C for 6 h in an open system with air flow, followed by dialysis purification. The high product yield was attributed to the addition of Na3PO4·12H2O as a base catalyst, which promoted the dehydration-condensation reaction between PG molecules. The dispersion of PG derived GQDs (PG-GQDs) in ethanol resulted in blue fluorescence with a full width at half maximum of 32 nm and a PLQY of 54%. Further purification of PG-GQDs by silica gel column chromatography improved the PLQY to 75%. Fourier-transform infrared spectroscopy, 1H nuclear magnetic resonance spectroscopy, and X-ray photoelectron spectroscopy confirmed that dehydration-condensation reactions occurred not only between PGs but also between GQDs and 1,2-pentanediol. The binding of 1,2-pentanediol to the edges of GQDs suppressed the stacking of GQDs and prevented concentration quenching, resulting in a high PLQY. PG-GQDs exhibited negative fluorescence solvatochromism, i.e., the fluorescence wavelength blue-shifted with increasing solvent polarity. Dispersion of PG-GQDs in N-methyl-2-pyrrolidone (MP) resulted in green fluorescence with a PLQY of 96%. Dispersion of PG-GQDs in water resulted in blue fluorescence and a low PLQY of 6% at pH 7, while the PLQY was more than 50% at pH ≥ 11. Using these properties, the sensing of water (pH 13) in MP was investigated. The results showed that as the water content was increased from 0% to 100%, the fluorescence color gradually changed from green to blue and the fluorescence wavelength continuously shifted from 514 nm to 466 nm, indicating their applicability in water sensing.

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Open system synthesis of narrow-bandwidth red-fluorescent carbon quantum dots with a function of multi-metal ion sensing

Rika Katakami, Kohei Sato, Akihiro Ogura, Ken-ichi Takao, Yoshiki Iso, Tetsuhiko Isobe

Journal of Materials Chemistry C (Journal of Materials Chemistry C)  11 ( 12 ) 4143 - 4152 2023

Research paper (scientific journal), Joint Work, Accepted,  ISSN  2050-7526

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Carbon quantum dots (CQDs) are environmentally friendly phosphors. However, there have been few reports on red-emitting CQDs with narrow-bandwidths, all of which were synthesized via solvothermal methods using autoclaves. Here, red-emitting CQDs were synthesized from 4,6-diaminoresorcinol dihydrochloride (DAR), which is an aromatic compound with electron-donating hydroxy and amino groups. The synthesis involved heating at 180 °C for 6 h in a high-boiling-point 1,2-pentanediol solvent in an open system without using autoclaves and catalysts. The DAR-derived-CQDs in ethanol exhibited red photoluminescence with a 0.14 eV full width at half-maximum that was comparable to that of narrow-bandwidth blue-fluorescent phloroglucinol (PG)-derived-CQDs. The red emission was attributed to a weakened quantum-size effect and electron-donating NH2 groups. The hydroxy groups of PG-derived-CQDs interacted with Al3+ and Fe3+ ions, resulting in fluorescence quenching. DAR-derived-CQDs have hydroxy and amino groups, which facilitate the fluorescence quenching for Al3+, Fe3+, Cu2+, and Pb2+ ions.

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Red-light-mediated Barton decarboxylation reaction and one-pot wavelength-selective transformations

Hiroki Yamamoto, Kohei Yamaoka, Ann Shinohara, Kouhei Shibata, Ken-ichi Takao, Akihiro Ogura

Chemical Science (Chemical Science)  14 ( 40 ) 11243 - 11250 2023

Research paper (scientific journal), Joint Work, Accepted,  ISSN  2041-6520

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In organic chemistry, selecting mild conditions for transformations and saving energy are increasingly important for achieving sustainable development goals. Herein, we describe a red-light-mediated Barton decarboxylation using readily available red-light-emitting diodes as the energy source and zinc tetraphenylporphyrin as the catalyst, avoiding explosive or hazardous reagents or external heating. Mechanistic studies suggest that the reaction probably proceeds via Dexter energy transfer between the activated catalyst and the Barton ester. Furthermore, a one-pot wavelength-selective reaction within the visible light range is developed in combination with a blue-light-mediated photoredox reaction, demonstrating the compatibility of two photochemical transformations based on mechanistic differences. This one-pot process expands the limits of the decarboxylative Giese reaction beyond polarity matching.

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In vivo imaging of fluorescent albumin modified with pyruvylated-human-type complex oligosaccharide reveals sialylation-like biodistribution and kinetics

Ryoichiro Fukuhara, Akihiro Ogura, Sho Yoshinaga, Takamasa Fukunaga, Takashi Kinoshita, Wataru Sumiyoshi, Yujiro Higuchi, Katsunori Tanaka, Kaoru Takegawa

Bioorganic & Medicinal Chemistry (Elsevier BV)  70   116943 - 116943 2022.09

Research paper (scientific journal), Joint Work, Accepted,  ISSN  0968-0896

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Both pyruvylation and sialylation onto the terminus of oligosaccharides of N-glycoproteins seem to be structurally and functionally similar with a property of conferring negative charge. However, detailed molecular characteristics of pyruvylation and sialylation in vivo were elusive. Here, to investigate an effect of terminal pyruvylation to N-glycan on in vivo biodistribution and kinetics, we prepared human serum albumin (HSA) modified with pyruvylated N-glycan (PvG), conjugated with HiLyte Fluor 750 (FL750-PvGHSA). In vivo imaging by using FL750-PvGHSA revealed that terminally pyruvylated N-glycoalbumin was excreted like sialylated N-glycoalbumin, suggesting that pyruvylation mimics sialylation in in vivo biodistribution and kinetics of N-glycoproteins. Terminal pyruvylation onto N-glycans can be a potential tool for a novel glycoengineering strategy.

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Asymmetric Synthesis of Cyclopentene Compounds Containing All-Carbon Quaternary Stereocenters by (3 + 2) Cycloaddition and Its Application in the Formal Synthesis of (R)-(−)-Puraquinonic Acid

Miho Oga, Yusei Takamatsu, Akihiro Ogura, Ken-ichi Takao

The Journal of Organic Chemistry (American Chemical Society ({ACS}))  87 ( 13 ) 8788 - 8795 2022.07

Research paper (scientific journal), Joint Work, Accepted,  ISSN  0022-3263

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A highly stereoselective (3 + 2) cycloaddition for the asymmetric synthesis of versatile cyclopentene compounds containing all-carbon quaternary stereocenters was developed. The phosphine-catalyzed reactions of alkynoates with α-alkylated electron-deficient alkenes bearing Oppolzer's camphorsultam showed high to excellent diastereoselectivities and perfect regioselectivities. The usefulness of this reaction was demonstrated in the concise formal synthesis of (R)-(-)-puraquinonic acid.

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Elucidation of structure-activity relationship of humulanolides and identification of humulanolide analog as a novel HSP90 inhibitor.

Junya Saegusa, Yoshiyuki Osada, Kazuki Miura, Yukiko Sasazawa, Akihiro Ogura, Ken-Ichi Takao, Siro Simizu

Bioorganic & medicinal chemistry letters (Bioorganic and Medicinal Chemistry Letters)  60   128589 - 128589 2022.03

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

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Humulanolides are natural products isolated from Asteriscus, and the isolation and total synthesis of many types of humulanolides have been reported. In this study, we evaluated anti-proliferative activity of twelve humulanolides against various human cancer cell lines and found that humulanolide analog E, which was newly designed and synthesized, exhibited the highest anti-proliferative activity. Structure-activity relationship analysis revealed that α,β-unsaturated carbonyl moieties in humulanolides play an important role for anti-proliferative activity. To identify molecular targets of humulanolide analog E, we investigated various cell-based and in vitro assays. Treatment with humulanolide analog E against human fibrosarcoma HT1080 cells increased the expression level of HSP70 protein and decreased the levels of AKT and CDK4, which are HSP90 client proteins. Moreover, humulanolide analog E inhibited refolding of denatured luciferase protein via suppression of HSP90 activity in vitro. These results suggest that humulanolide analog E possesses the anti-proliferative activity against human cancer cells by inhibiting HSP90 functions.

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Diaryliodonium Salt-Based Synthesis of N-Alkoxyindolines and Further Insights into the Ishikawa Indole Synthesis

Kouhei Shibata, Ken-ichi Takao, Akihiro Ogura

The Journal of Organic Chemistry (American Chemical Society ({ACS}))  86 ( 15 ) 10067 - 10087 2021.08

Research paper (scientific journal), Joint Work, Accepted,  ISSN  0022-3263

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A diaryliodonium salt-based strategy enabled the first systematic synthesis of rarely accessible N-alkoxyindolines. Mechanistic analyses suggested that the reaction likely involves reductive elimination of iodobenzene from iodaoxazepine via a four-membered transition state, followed by Meisenheimer rearrangement. Substrates with N-carbamate protection afforded indole in a manner similar to that of the Ishikawa indole synthesis. Preinstallation of a stannyl group as an iodonium salt precursor greatly expanded the substrate scope, and further mechanistic insights are discussed.

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Asymmetric Diels–Alder reaction between furans and propiolates

Ogura A., Ito T., Moriya K., Horigome H., Takao K.

Tetrahedron Letters (Elsevier {BV})  72   153075 - 153075 2021.05

Research paper (scientific journal), Joint Work, Lead author, Corresponding author, Accepted,  ISSN  00404039

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We report the first asymmetric Diels–Alder reaction between furan and propiolates. Propiolate, a dienophile, was equipped with an Evans’ auxiliary and a sulfonyl group to control and facilitate diastereoselective cycloaddition. Treatment with furan as a diene and aluminium Lewis acid afforded a 7-oxabicyclo[2.2.1]heptadiene skeleton diastereoselectively. The origin of diastereoselectivity can be explained by chelation of aluminium center to carbonyl groups and oxygen of furan. Friedel–Crafts-type products were obtained when pyrrole was used as diene.

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Glycothermally Synthesized Carbon Dots with Narrow-Bandwidth and Color-Tunable Solvatochromic Fluorescence for Wide-Color-Gamut Displays

Taishu Yoshinaga, Momoka Shinoda, Yoshiki Iso, Tetsuhiko Isobe, Akihiro Ogura, Ken-ichi Takao

ACS Omega (American Chemical Society ({ACS}))  6 ( 2 ) 1741 - 1750 2021.01

Research paper (scientific journal), Joint Work, Accepted,  ISSN  2470-1343

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Fluorescent carbon dots (CDs) represent a promising eco-friendly next-generation phosphor. However, most CDs exhibit broad photoluminescence (PL) spectra [full width at half-maximum (fwhm) over 60 nm]; few works on CDs with sharp PL spectra (fwhm less than 40 nm) have been reported. In addition, their syntheses and color tuning require harsh conditions of high temperatures, long reaction times, and high pressures with catalysts. Here, we successfully prepared narrow-bandwidth emissive CDs (fwhm of 27-40 nm) from phloroglucinol in a glycol solvent of 1,2-pentanediol at temperatures as low as 180 °C for a reaction duration of as short as 6 h under ambient conditions without any catalysts via an open reaction system in which dehydration and condensation reactions among phloroglucinol molecules were enhanced. We shifted the emission peak from 463 to 511 nm by selecting seven kinds of solvents with different polarities, that is, emission colors could be tuned from blue to green by taking advantage of fluorescence solvatochromism. The CD-dispersed polymer films showed a similar solvatochromic behavior and sharp PL spectra, verifying the feasibility of applying the CDs to displays with a wide color gamut.

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Red-Light-Mediated Barton–McCombie Reaction

Akihiro Ogura, Naoki Ichii, Kouhei Shibata, Ken-ichi Takao

Bulletin of the Chemical Society of Japan (The Chemical Society of Japan)  93 ( 7 ) 936 - 941 2020.07

Research paper (scientific journal), Joint Work, Lead author, Corresponding author, Accepted,  ISSN  00092673

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Stereoselective Synthesis of the Tricyclic Core of (-)-Callophycoic Acid A

Akihiro Sakama, Rika Kameshima, Yuko Motohashi, Wataru Sumida, Yuta Unno, Keisuke Yoshida, Akihiro Ogura, Ken Ichi Takao

Journal of Organic Chemistry (American Chemical Society ({ACS}))  85 ( 5 ) 3245 - 3264 2020.03

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

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Identification of vibsanin A analog as a novel HSP90 inhibitor

Kazuki Miura, Wataru Matsuki, Akihiro Ogura, Ken-ichi Takao, Siro Simizu

Bioorganic & Medicinal Chemistry (Elsevier {BV})  28 ( 2 ) 115253 - 115253 2020.01

Research paper (scientific journal), Joint Work, Accepted,  ISSN  09680896

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Identification of topoisomerases as molecular targets of cytosporolide C and its analog

Keisuke Otake, Kana Yamada, Kazuki Miura, Yukiko Sasazawa, So Miyazaki, Yuki Niwa, Akihiro Ogura, Ken-ichi Takao, Siro Simizu

Bioorganic & Medicinal Chemistry (Elsevier {BV})  27 ( 15 ) 3334 - 3338 2019.08

Research paper (scientific journal), Joint Work, Accepted,  ISSN  09680896

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Total Syntheses of (+)‐Aquatolide and Related Humulanolides

Ken-ichi Takao, Hirotaka Kai, Ai Yamada, Yuuki Fukushima, Daisuke Komatsu, Akihiro Ogura, Keisuke Yoshida

Angewandte Chemie (Wiley)  131 ( 29 ) 9956 - 9960 2019.07

ISSN  1521-3757

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Total Syntheses of (+)-Aquatolide and Related Humulanolides

Ken-ichi Takao, Hirotaka Kai, Ai Yamada, Yuuki Fukushima, Daisuke Komatsu, Akihiro Ogura, Keisuke Yoshida

Angewandte Chemie International Edition (Wiley)  58 ( 29 ) 9851 - 9855 2019.06

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

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Herein, the total syntheses of (+)-aquatolide, a humulane-derived sesquiterpenoid lactone, and five other related humulanolides are described. The key reactions in these syntheses are a cascade metathesis reaction of cyclobutenecar-boxylate to construct a γ-butenolide with an unsaturated aldehyde side chain, an intramolecular Nozaki-Hiyama-Takai-Kishi reaction to form an all-trans-humulene lactone skeleton, and a biosynthesis-inspired [2 + 2] photocycloaddition to provide a bridged 5/5/4/8-ring system. A cycloaddition giving a 5/4/4/7-ring system was also found. In addition, biological studies were conducted using the synthesized samples.

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Studies toward the Synthesis of Perforatumone: Synthesis of the 7-Oxabicyclo[4.2.1]nonane-8,9-dione Core

Ken-ichi Takao, Tatsuki Nakajima, Keita Takiguchi, Keisuke Yoshida, Akihiro Ogura

HETEROCYCLES (Japan Institute of Heterocyclic Chemistry)  99 ( 1 ) 661 - 668 2019

Research paper (scientific journal), Joint Work, Last author, Accepted,  ISSN  03855414

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