KEIO RESEARCHERS INFORMATION SYSTEM

Career 【 Display / hide 】

Career 【 Display / hide 】

• 2005.04

  -

  2006.03

  harvard University, Departmernt of Chemistry and Chemical Biology, Postdoctoral Fellow

• 2006.04

  -

  2010.03

  The University of Tokyo, Graduate School of Pharmaceutical Sciences, Assistant Professor

• 2010.04

  -

  2010.12

  Institute of Microbial Chemistry, Laboratory of Synthetic Organic Chemnistry, Researcher

• 2010.04

  -

  2017.03

  Rikkyo University, Department of Science, Adjunct Lecturer

• 2011.01

  -

  2013.03

  Insttitute of Microbial Chemistry, Laboratory of Synthetic Organic Chemistry, Senior Researcher

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Academic Background 【 Display / hide 】

Academic Background 【 Display / hide 】

• 1996.04

  -

  2000.03

  The University of Tokyo, Department of Pharmaceutical Sciences

  University, Graduated

• 2000.04

  -

  2002.03

  The University of Tokyo, Graduate School of Pharmaceutical Sciences

  Graduate School, Completed, Master's course

• 2002.04

  -

  2005.03

  The University of Tokyo, Graduate School of Pharmaceutical Sciences

  Graduate School, Completed, Doctoral course

Academic Degrees 【 Display / hide 】

Academic Degrees 【 Display / hide 】

• The University of Tokyo, The University of Tokyo, Coursework, 2005.03

Licenses and Qualifications 【 Display / hide 】

Licenses and Qualifications 【 Display / hide 】

• Pharmacist, 2000.09

• senior [first class] radiation protection supervisor, 2012.04

Research Areas 【 Display / hide 】

Research Areas 【 Display / hide 】

• Nanotechnology/Materials / Structural organic chemistry and physical organic chemistry

• Life Science / Bioorganic chemistry

Books 【 Display / hide 】

Books 【 Display / hide 】

• Interplay of diamides and rare earth metals: Specific molecular spaces and catalytic activity

  Kumagai N., Shibasaki M., Designed Molecular Space in Material Science and Catalysis, 2018.01

  　View Summary

  A catalytic system comprising functionalized small diamides and rare earth metals (REs) exerts intriguing catalytic properties that are dictated by dynamic construction of flexible molecular spaces. The dynamic interaction of diamides and REs is characterized by broad applicability to distinct reaction systems as well as notable switchable catalysis. Structural modification of the diamide allows for enhanced intermolecular interactions to afford a self-assembled solid-phase catalyst with a specific molecular space that engages in heterogeneous asymmetric catalysis with a continuous-flow platform.

• Chiral Bimetallic Lewis Acids

  Shibasaki M., Kumagai N., Topics in Organometallic Chemistry, 2018

  　View Summary

  Here, we review the utility of chiral bimetallic (multimetallic) Lewis acidic complexes in catalytic asymmetric transformations. Bimetallic complexes are endowed with dual catalytic functions that synergistically activate multiple substrates and functionalities. This cooperative activation mode is particularly effective for activating low reactivity substrates in a highly stereoselective manner without the aid of stoichiometric activating reagents. The privileged bimetallic catalysts presented here highlight the importance of catalyst design in the development of widely applicable catalytic systems.

Papers 【 Display / hide 】

Papers 【 Display / hide 】

• Quinoline-Directed Folding in Anilide–Quinoline Hybrids: Length-Controlled Three-Dimensional Conformational Diversity

  Xu W., Takeda A., Kumagai N.

  Jacs Au 6 ( 6 ) 3527 - 3535 2026.06

  　View Summary

  Quinoline-based aromatic oligoamide foldamers composed of anilide (A) and quinoline (Q) units, in which amide-bond formation at the quinoline 8-position provides access to cyclic and acyclic architectures, exhibit distinct folding behaviors. The cyclic series A(n)Q(n) (n = 2–6) was obtained by one-pot cyclooligomerization or by stepwise assembly followed by intramolecular amidation. Structural analyses revealed a pronounced ring-size dependence of conformation and symmetry, ranging from symmetric macrocycles to unsymmetric, partially helical folds. In particular, the hexamer A6Q6 exhibits an unusual two-state conformational equilibrium in solution and was isolated in the solid state as both a partially helical unsymmetric conformer and a highly symmetric S<inf>6</inf> cubic conformer featuring a hydrophobic internal cavity. In parallel, the corresponding acyclic oligomers NH<inf>2</inf>-A(n)Q(n)-CO<inf>2</inf>H (n = 3–6) adopt well-defined helical structures in the solid state and retain compact folded conformations in solution, as supported by NMR, H/D-exchange, and NOE analyses. The helical fold generates a confined cavity comparable in size to that of a 12-membered ring. These findings establish anilide–quinoline hybrids as a versatile platform for size-programmed macrocycles, stable aromatic helices, and functional foldamer architectures.

  • Access to Document (DOI)

• TriQuinazoline and Related Quinoline/Quinazoline Cyclic Trimers: Unified Synthesis, Planar Discotic Architecture, and Proton Dynamics in an Atomic-Scale Cavity

  Sakurai T., Tsutsumi R., Kumagai N.

  Chemistry of Materials 38 ( 5 ) 2453 - 2463 2026.03

  ISSN  08974756

  　View Summary

  Heteroatom-doped graphitic materials, particularly those bearing nitrogen, have attracted considerable attention because of their unique physicochemical properties, which are unattainable in pristine carbon frameworks. To rigorously investigate the effects of doping and to enable fine-tuning of their functions at the atomic scale, bottom-up synthesis of well-defined molecular surrogates provides a powerful approach. Herein, we report the design, synthesis, and physicochemical characterization of a series of quinoline/quinazoline cyclic trimers, TriQuinoline (TQ, Q3), Q2Qz1, Q1Qz2, and TriQuinazoline (TQz, Qz3), featuring an atomic-sized central cavity surrounded by three pyridinic nitrogens that mirrors the local topology of nitrogen-doped graphene defects. A modular synthetic strategy enabled facile access to all of the quinazoline-containing congeners. Systematic X-ray analysis and computational studies revealed increasing molecular planarity with increasing quinazoline incorporation, arising from stepwise elimination of destabilizing CH···HC contacts and the emergence of favorable CH···N interactions. Spectroscopic and theoretical studies demonstrated that quinazoline substitution progressively decreases the proton affinity at the central cavity owing to the electron-withdrawing nature of the quinazoline units, which markedly accelerates proton exchange. Even with these electronic modifications, supramolecular association with polycyclic aromatics, such as coronene and [12]cycloparaphenylene ([12]CPP), substantially remained preserved upon quinazoline incorporation. These findings highlight the cooperative interplay of structural planarity and heteroatom substitution in dictating the properties of discotic heteroaromatics, offering a versatile platform for material design.

  • Access to Document (DOI)

• Insights into coordination and (semi-)rigidity in the molecular design of bicyclic heterocycle frameworks

  Kobayashi T., Sakurai T., Kumagai N.

  Chemistry Letters 55 ( 2 )  2026.02

  ISSN  03667022

  　View Summary

  Macrocyclic compounds, exhibiting unique properties arising from their large-ring frameworks, have captivated the attention of organic chemists over the last few decades. These molecules serve specific functions across disciplines, including synthetic chemistry, materials science, and biology. Representative molecules in this category, including crown ethers, calix[n]arenes, and porphyrinoids composed of ether/phenol/pyrrole subunits, exhibit unparalleled structural and functional diversity. In contrast, macrocycles exploiting quinoline/quinazoline as key building blocks to construct specific macrocyclic architectures have received limited attention and are much less explored. In this Highlight Review, we summarize our recent advances in oligo-quinoline/quinazoline macrocycles. Emphasis is focused on synthetic strategies, structural features, and emerging applications in organometallic, supramolecular, and photophysical chemistry. We anticipate that these collective results will guide new molecular designs within the broader family of heterocycle-based macrocycles.

  • Access to Document (DOI)

• Revisiting C4N4 Fluorophore: Theoretical Elucidation of the Origin of Fluorescent Properties of 2,5-Diaminopyrimidines and Strategic Applications to Pd Detection

  Kohei M., Kondo I., Kawamura G., Harabuchi Y., Maeda S., Kumagai N.

  Chemistry A European Journal  2026

  ISSN  09476539

  　View Summary

  Compact organic fluorophores are attractive scaffolds for probe design, yet their emission is often compromised by efficient nonradiative decay. Here, we introduce 2,5-diaminopyrimidine-based C4N4 as an intrinsically emissive, exceptionally small platform, which remains bright without extended π-conjugation. Systematic substitution at 4,6-positions with alkyl, alkenyl, and alkynyl groups reveals robust emission for alkyl and alkynyl derivatives, and a striking bimodality for alkenyls. TDDFT combined with ES/SC-AFIR mapped the S<inf>1</inf>→S<inf>0</inf> internal-conversion landscape, providing a rationale for substituent-dependent relaxation behavior. Manipulation at the 5-position allowed for independent trigger-responsive emission behavior. This orthogonal design, where the 4,6-substituted C4N4 core serves as the fluorophore and the 5-position operates as ON/OFF gate, enabled the development of turn-on probes for Pd²⁺.

  • Access to Document (DOI)

• Catalyst-Controlled Chemoselective Transformation of Cyanopyridines over Cyanoarenes Enabled by a DATB–Phenothiazine Hybrid Photocatalyst

  Kinase Y., Tsutsumi R., Kumagai N.

  Synlett  2026

  ISSN  09365214

  　View Summary

  A catalyst-dependent chemoselective photoredox reaction of cyanopyridines and cyanoarenes with N-aryl tertiary amines is described. In competitive reactions under visible-light irradiation, a conventional iridium photocatalyst preferentially promoted coupling of the cyanoarene component, whereas phenothiazine-based catalyst systems, including a DATB–phenothiazine hybrid, favored formation of cyanopyridine-derived products. The cyanopyridine-selective product distribution was observed across several combinations of amines, cyanopyridines, and competing cyanoarenes. These results show that the identity of the photocatalyst can govern the relative substrate preference of closely related cyano(hetero)arene acceptors in photoredox catalysis.

  • Access to Document (DOI)

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Papers, etc., Registered in KOARA 【 Display / hide 】

Papers, etc., Registered in KOARA 【 Display / hide 】

• Porphyrin 2.0 : chemistry of warped-porphyrin

  Kumagai, Naoya

  科学研究費補助金研究成果報告書 2023

• Strategic molecular design aiming at streamlined chemical transformations

  Kumagai, Naoya

  科学研究費補助金研究成果報告書 2022

• Medicinal chemistry based on exotic water-soluble aromatic molecule TriQuinoline

  Kumagai, Naoya

  福澤諭吉記念慶應義塾学事振興基金事業報告集 (福澤基金運営委員会)  2022

Reviews, Commentaries, etc. 【 Display / hide 】

Reviews, Commentaries, etc. 【 Display / hide 】

• Author Correction: TriQuinoline (Nature Communications, (2019), 10, 1, (3820), 10.1038/s41467-019-11818-1)

  Adachi S., Shibasaki M., Kumagai N.

  Nature Communications (Nature Communications)  11 ( 1 )  2020.12

  　View Summary

  An amendment to this paper has been published and can be accessed via a link at the top of the paper.

  • Access to Document (DOI)

Presentations 【 Display / hide 】

Presentations 【 Display / hide 】

• Revisiting C4N4: 蛍光発光メカニズムの計算化学的解明と重金属検出プローブへの応用

  公平実希、川村剛、原渕祐、前田理、熊谷直哉

  [Domestic presentation]  日本化学会第105春季年会, 

  2025.03

  , 

  Oral presentation (general)

• 新奇ハニカム型大環状キノリンオリゴマーの合成

  田代奨吾，Wei Xu，熊谷直哉

  [Domestic presentation]  日本化学会第105春季年会, 

  2025.03

  , 

  Oral presentation (general)

• カチオン性置換基を有するTriQuinoline（TQ）誘導体による改良型G4リガンド創製

  狩俣太雅、山崎洋子、Wei Xu、熊谷直哉

  [Domestic presentation]  日本薬学会第145年会, 

  2025.03

  , 

  Oral presentation (general)

• 非平面型ポルフィリノイドoxa-TEtraQuinolineの合成と金属捕捉挙動

  小林透威、熊谷直哉

  [Domestic presentation]  日本薬学会第145年会, 

  2025.03

  , 

  Oral presentation (general)

• 大環状3量体分子[HyD-Py]3の合成とカゴ型化合物への応用

  鶴岡航太朗、野崎雅人、工藤駿、熊谷直哉

  [Domestic presentation]  日本化学会第105春季年会, 

  2025.03

  , 

  Oral presentation (general)

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Research Projects of Competitive Funds, etc. 【 Display / hide 】

Research Projects of Competitive Funds, etc. 【 Display / hide 】

• Functional Molecular Sophistication Driven by Starategic Molecular Design

  2026.04

  -

  2029.03

  基盤研究(B), Principal investigator

• 軽元素分子触媒戦略によるアミド生産技術の刷新

  2024.12

  -

  2027.03

  科学技術振興機構（JST）, 研究成果最適展開支援プログラム（A-STEP）産学共同 ステージⅠ（育成フェーズ）, Joint research, Principal investigator

• Expeditious Sophistication of Seed Molecular Entities Aided by Theory and Machine Learning

  2023.04

  -

  2026.03

  学術変革領域研究(B), Principal investigator

• Diversification of Molecular Functions via Unique Molecular Design

  2023.04

  -

  2026.03

  基盤研究(B), Principal investigator

• Porphyrin 2.0: Chemistry of Warped-Porphyrin

  2022.06

  -

  2024.03

  MEXT,JSPS, Grant-in-Aid for Scientific Research, 挑戦的研究（萌芽）, Principal investigator

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Awards 【 Display / hide 】

Awards 【 Display / hide 】

• Mukaiyama Award

  2023

  Type of Award： International academic award (Japan or overseas)

• Merck Banyu Lectureship Award（MBLA）

  2018

  Type of Award： International academic award (Japan or overseas)

• 三井化学触媒科学奨励賞

  2014

  Type of Award： International academic award (Japan or overseas)

• Thieme Chemistry Journal Award

  2013

  Type of Award： International academic award (Japan or overseas)

• 文部科学大臣表彰若手科学者賞

  2013

  Type of Award： International academic award (Japan or overseas)

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Courses Taught 【 Display / hide 】

Courses Taught 【 Display / hide 】

• STUDY OF MAJOR FIELD (MOLECULAR DESIGN)

  2026

• BACHELOR'S THESIS

  2026

• DRUG SYNTHESIS LABORATORY COURSE

  2026

• ADVANCED MEDICINAL AND ORGANIC CHEMISTRY

  2026

• MEDICINAL CHEMISTRY 2

  2026

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