MISC - 好光　健彦

Red-Light-Promoted Radical Cascade Reaction to Access Tetralins and Dialins Enabled by Zinc(II)porphyrin, A Light-Flexible Catalyst 査読

Yusuke Okanishi, Otoki Takemoto, Sanpou Kawahara, Satoshi Hayashi, Toshikatsu Takanami, Takehiko Yoshimitsu

Organic Letters   2024年4月

　詳細を見る

担当区分：最終著者,　責任著者   記述言語：英語   掲載種別：速報，短報，研究ノート等（学術雑誌）   出版者・発行元：American Chemical Society (ACS)  

DOI： 10.1021/acs.orglett.4c01112

researchmap

Osteopontin promotes age-related adipose tissue remodeling through senescence-associated macrophage dysfunction 査読 国際共著 国際誌

Daigo Sawaki, Yanyan Zhang, Amel Mohamadi, Maria Pini, Zaineb Mezdari, Larissa Lipskaia, Suzain Naushad, Lucille Lamendour, Dogus Murat Altintas, Marielle Breau, Hao Liang, Maissa Halfaoui, Thaïs Delmont, Mathieu Surenaud, Déborah Rousseau, Takehiko Yoshimitsu, Fawzia Louache, Serge Adnot, Corneliu Henegar, Philippe Gual, Gabor Czibik, Geneviève Derumeaux

JCI Insight   8 ( 8 )   2023年4月

　詳細を見る

記述言語：英語   掲載種別：速報，短報，研究ノート等（学術雑誌）   出版者・発行元：American Society for Clinical Investigation  

DOI： 10.1172/jci.insight.145811

researchmap

Radical-Based Route to Functionalized Tetralin: Formal Total Synthesis of (±)-Hamigeran B 国際誌

Yusuke Okanishi, Tohru Ishikawa, Takuya Jinnouchi, Satoshi Hayashi, Toshikatsu Takanami, Hiroshi Aoyama, Takehiko Yoshimitsu

The Journal of Organic Chemistry   88 ( 2 )   1085 - 1092   2023年1月

　詳細を見る

出版者・発行元：American Chemical Society (ACS)  

DOI： 10.1021/acs.joc.2c02552

researchmap

Organic redox cascade cyclization of 2-alkynylquinones by ascorbic acid in combination with a copper catalyst and its application to formal synthesis of liphagal 国際共著 国際誌

Taejoo Jeong, Yusuke Okanishi, Sora Yotsui, In Su Kim, Takehiko Yoshimitsu

New Journal of Chemistry   47 ( 7 )   3425 - 3429   2023年

　詳細を見る

出版者・発行元：Royal Society of Chemistry (RSC)  

The combination of a quinone-ascorbic acid organic redox reaction and a concomitant copper catalysis in situ enables new approach to hydroxybenzofurans with structural variations.

DOI： 10.1039/d2nj05724g

researchmap

A Virtual Screening Platform Identifies Chloroethylagelastatin A as a Potential Ribosomal Inhibitor 査読 国際共著

T. R. Caulfield, K. E. Hayes, Y. Qiu, M. Coban, J. Seok Oh, A. L. Lane, T. Yoshimitsu, L. Hazlehurst, J. A. Copland, H. W. Tun

10   1047   2020年10月

　詳細を見る

記述言語：英語   掲載種別：速報，短報，研究ノート等（学術雑誌）  

DOI： 10.3390/biom10101407

DOI： 10.3390/biom10101407

A Virtual Screening Platform Identifies Chloroethylagelastatin A as a Potential Ribosomal Inhibitor 査読 国際共著 国際誌

Thomas R. Caulfield, Karen E. Hayes, Yushi Qiu, Mathew Coban, Joon Seok Oh, Amy L. Lane, Takehiko Yoshimitsu, Lori Hazlehurst, John A. Copland, Han W. Tun

Biomolecules   10 ( 10 )   1407 - 1407   2020年10月

　詳細を見る

記述言語：英語   掲載種別：速報，短報，研究ノート等（学術雑誌）   出版者・発行元：MDPI AG  

Chloroethylagelastatin A (CEAA) is an analogue of agelastatin A (AA), a natural alkaloid derived from a marine sponge. It is under development for therapeutic use against brain tumors as it has excellent central nervous system (CNS) penetration and pre-clinical therapeutic activity against brain tumors. Recently, AA was shown to inhibit protein synthesis by binding to the ribosomal A-site. In this study, we developed a novel virtual screening platform to perform a comprehensive screening of various AA analogues showing that AA analogues with proven therapeutic activity including CEAA have significant ribosomal binding capacity whereas therapeutically inactive analogues show poor ribosomal binding and revealing structural fingerprint features essential for drug-ribosome interactions. In particular, CEAA was found to have greater ribosomal binding capacity than AA. Biological tests showed that CEAA binds the ribosome and contributes to protein synthesis inhibition. Our findings suggest that CEAA may possess ribosomal inhibitor activity and that our virtual screening platform may be a useful tool in discovery and development of novel ribosomal inhibitors.

DOI： 10.3390/biom10101407

researchmap

Total Synthesis of (±)-Liphagal via Organic-Redox-Driven Palladium-Catalyzed Hydroxybenzofuran Formation 査読

Eriko Tao, Masaki Inoue, Taejoo Jeong, In Su Kim, Takehiko Yoshimitsu

The Journal of Organic Chemistry   85 ( 14 )   9064 - 9070   2020年7月

　詳細を見る

担当区分：最終著者,　責任著者   記述言語：英語   掲載種別：速報，短報，研究ノート等（学術雑誌）   出版者・発行元：American Chemical Society (ACS)  

DOI： 10.1021/acs.joc.0c00965

researchmap

Chemical Syntheses and Biological Studies of Agelastatin A, a Bioactive Marine Heterocycle Gifted from Nature 招待 査読

Takehiko Yoshimitsu

HETEROCYCLES   100 ( 11 )   1735 - 1735   2020年5月

　詳細を見る

担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：記事・総説・解説・論説等（学術雑誌）   出版者・発行元：The Japan Institute of Heterocyclic Chemistry  

DOI： 10.3987/rev-20-929

researchmap

天然物合成における窒素フリーラジカル種の戦略的活用：アゲラスタチンAの全合成 査読

好光 健彦

有機合成化学協会誌   77 ( 5 )   472 - 481   2019年5月

　詳細を見る

記述言語：日本語   掲載種別：記事・総説・解説・論説等（学術雑誌）  

researchmap

Ru(II)-Catalyzed C–H Aminocarbonylation of N-(Hetero)aryl-7-azaindoles with Isocyanates

Jeong, T, Lee, S.-H, Chun, R, Han, S, Han, S.-H, Jeon, Y.-U, Park, J, Yoshimitsu, T, Mishra, N. K, Kim, I.-S

J. Org. Chem.   83 ( 8 )   4641 - 4649   2018年4月

　詳細を見る

記述言語：英語  

DOI： 10.1021/acs.joc.8b00388

Scopus

researchmap

Visceral Adipose Tissue Drives Cardiac Aging Through Modulation of Fibroblast Senescence by Osteopontin Production 国際共著 国際誌

Sawaki, D, Czibik, G, Pini, M, Ternacle, J, Suffee, N, Mercedes, R, Marcelin, G, Surenaud, M, Marcos, E, Gual, P, Clement, K, Hue, S, Adnot, S, Hatem, S. N, Tsuchimochi, I, Yoshimitsu, T, Henegar, C, Derumeaux, G

Circulation   138 ( 8 )   809 - 822   2018年

　詳細を見る

記述言語：英語  

DOI： 10.1161/CIRCULATIONAHA.117.031358

PubMed

researchmap

Total Synthesis of (-)-Agelastatin A: An SH2’ Radical Azidation Strategy

Tsuchimochi, I, Kitamura, Y, Aoyama, H, Akai, S, Nakai, K, Yoshimitsu, T

Chemical Communications   2018年

　詳細を見る

DOI： 10.1039/C8CC05697H

researchmap

2-aminoethoxydiphenyl borate provides an anti-oxidative effect and mediates cardioprotection during ischemia reperfusion in mice

Hirofumi Morihara, Masanori Obana, Shota Tanaka, Ikki Kawakatsu, Daisuke Tsuchiyama, Shota Mori, Hiroshi Suizu, Akiko Ishida, Rumi Kimura, Izuru Tsuchimochi, Makiko Maeda, Takehiko Yoshimitsu, Yasushi Fujio, Hiroyuki Nakayama

PLoS ONE   12 ( 12 )   650 - 659   2017年12月

　詳細を見る

記述言語：英語   出版者・発行元：Public Library of Science  

Excessive levels of reactive oxygen species (ROS) and impaired Ca2+ homeostasis play central roles in the development of multiple cardiac pathologies, including cell death during ischemia-reperfusion (I/R) injury. In several organs, treatment with 2-aminoethoxydiphenyl borate (2-APB) was shown to have protective effects, generally believed to be due to Ca2+ channel inhibition. However, the mechanism of 2-APB-induced cardioprotection has not been fully investigated. Herein we investigated the protective effects of 2-APB treatment against cardiac pathogenesis and deciphered the underlying mechanisms. In neonatal rat cardiomyocytes, treatment with 2-APB was shown to prevent hydrogen peroxide (H2O2) -induced cell death by inhibiting the increase in intracellular Ca2+ levels. However, no 2-APB-sensitive channel blocker inhibited H2O2-induced cell death and a direct reaction between 2-APB and H2O2 was detected by 1H-NMR, suggesting that 2-APB chemically scavenges extracellular ROS and provides cytoprotection. In a mouse I/R model, treatment with 2-APB led to a considerable reduction in the infarct size after I/R, which was accompanied by the reduction in ROS levels and neutrophil infiltration, indicating that the anti-oxidative properties of 2-APB plays an important role in the prevention of I/R injury in vivo as well. Taken together, present results indicate that 2-APB treatment induces cardioprotection and prevents ROS-induced cardiomyocyte death, at least partially, by the direct scavenging of extracellular ROS. Therefore, administration of 2-APB may represent a promising therapeutic strategy for the treatment of ROS-related cardiac pathology including I/R injury.

DOI： 10.1371/journal.pone.0189948

Scopus

PubMed

researchmap

Regioselective Rearrangement of 4,4-Disubstituted 2-Hydroxycyclohexa-2,5-Dienones under Deoxyfluorination Conditions

Keita Takubo, Ahmed A. B. Mohamed, Takafumi Ide, Kazuyuki Saito, Takashi Ikawa, Takehiko Yoshimitsu, Shuji Akai

JOURNAL OF ORGANIC CHEMISTRY   82 ( 24 )   13141 - 13151   2017年12月

　詳細を見る

記述言語：英語   出版者・発行元：AMER CHEMICAL SOC  

The dienone-phenol rearrangement is a useful tool for the synthesis of highly substituted phenols. In our previous study of the rearrangement of 4,4-disubstituted 2-hydroxycyclohexa-2,5-dienone under deoxyfluorination conditions, bond migration proceeded with very poor regioselectivity. In this paper, an acid-mediated rearrangement, of O-perfluoroalkylsulfonyl difluorides with regioselective migration toward the beta'-carbon is reported. This method allowed the synthesis of a fluorinated analog of allocolchicinoids with improved total yield. Successful application to other substrates was also demonstrated.

DOI： 10.1021/acs.joc.7b02208

Web of Science

researchmap

Compounds, compositions, and methods of agelastatin alkaloids: patent evaluation of WO2015042239 (A1) 国際共著 国際誌

Takehiko Yoshimitsu, Han W. Tun

EXPERT OPINION ON THERAPEUTIC PATENTS   27 ( 2 )   113 - 119   2017年2月

　詳細を見る

記述言語：英語   出版者・発行元：TAYLOR & FRANCIS LTD  

Agelastatins are a family of tetracyclic alkaloids isolated from marine sponges. The patent examined in this publication covers the chemical synthesis of agelastatins A to F and eight analogues and their therapeutic use against hematologic malignancies. The claim on the chemical synthesis features a novel biomimetic cyclization of a tricyclic precursor, which streamlines scalable access to agelastatins and their analogues. This new synthetic approach can potentially expedite the research on these compounds for therapeutic use against cancers by making them more easily available. The claim on the therapeutic use against hematologic malignancies is based on the in vitro cytotoxicity against a limited number of cell lines and can be further strengthened by in vivo therapeutic evaluations focusing on specific hematologic malignancies. The comparative evaluation of the cytotoxicities of the natural alkaloids described in the application greatly enhances the understanding of their structure-activity relationships (SARs) relevant to the development of novel medicinal leads. Overall, the patent application is strong and has the potential to advance the rapidly expanding agelastatin research.

DOI： 10.1080/13543776.2017.1273902

Web of Science

researchmap

Radical Cyclization Strategies in Total Syntheses of Bioactive Fused Cyclic Natural Products

Takehiko Yoshimitsu

JOURNAL OF SYNTHETIC ORGANIC CHEMISTRY JAPAN   74 ( 4 )   350 - 359   2016年4月

　詳細を見る

記述言語：日本語   掲載種別：書評論文，書評，文献紹介等   出版者・発行元：SOC SYNTHETIC ORGANIC CHEM JPN  

The present article discusses our recent endeavors on natural product syntheses wherein radical reactions are strategically employed to access fused carbocycles. Particular emphasis is placed on the radical cyclizations that made it possible to establish the unique bond connectivity and functionalities of the target natural products. The radical chemistry-based approaches to platencin and clavilactone B are discussed here to show the utility of titanocene (III)-mediated epoxy enone cyclization, decarboxylative radical cyclization of an alkynyl carboxylic acid derivative with lead (IV) in 1,4-dioxane, and samarium (II)-mediated radical cyclization-fragmentation of an unsaturated keto ester, all of which serve as versatile means to elaborate the natural products.

Web of Science

researchmap

Diversity Oriented Synthesis of Allocolchicinoids with Fluoro and/or Oxygen Substituent(s) on the C-Ring from a Single Common Intermediate

Keita Takubo, Kazunori Furutsu, Takafumi Ide, Hiroyuki Nemoto, Yuko Ueda, Kazutake Tsujikawa, Takashi Ikawa, Takehiko Yoshimitsu, Shuji Akai

EUROPEAN JOURNAL OF ORGANIC CHEMISTRY   2016 ( 8 )   1562 - 1576   2016年3月

　詳細を見る

記述言語：英語   出版者・発行元：WILEY-V C H VERLAG GMBH  

Allocolchicinoids, with a distinct polyoxygenated dibenzocycloheptane skeleton, attract much attention as potential candidate anticancer drugs. In this study, eight C-ring fluorinated analogues of allocolchicinoids, seven C-ring oxygen-substituted analogues, and known compounds N-acetylcolchinol and NSC 51046 were synthesized as racemates from a single common intermediate by using either the deoxyfluorination/migration domino reaction or acid-promoted migration as the key step. Among the products obtained, some of the fluorinated derivatives strongly inhibited the growth of prostate DU145 and pancreas Panc 1 cancer cell lines with efficacy comparable to or better than those of N-acetylcolchinol and NSC 51046. They were also less toxic against a non-cancerous cell line than the known compounds were.

DOI： 10.1002/ejoc.201501624

Web of Science

researchmap

生物活性縮環天然物の全合成におけるラジカル環化戦略

好光健彦

有機合成化学協会誌   74   350 - 359   2016年

　詳細を見る

DOI： 10.5059/yukigoseikyokaishi.74.350

researchmap

解説「Grob型環開裂」

有機合成化学協会誌   74   379 - 379   2016年

　詳細を見る

researchmap

Total Synthesis of Clavilactone B: A Radical Cyclization− Fragmentation Strategy

H. Suizu, D. Shigeoka, H. Aoyama, T. Yoshimitsu

Org. Lett.   17 ( 1 )   126 - 129   2015年1月

　詳細を見る

記述言語：英語  

DOI： 10.1021/ol503356m

Web of Science

researchmap

A commentary on‘Classic Addition Reaction Gets A Makeover’ in Science & Technology, News of The Week in Chemical & Engineering News

Takehiko Yoshimitsu

Chemical & Engineering News   93 ( 3 )   2015年

　詳細を見る

researchmap

Enantiospecific Synthesis and Cytotoxicity Evaluation of Ligudentatol: A Programmed Aromatization Approach to the 2,3,4-Trisubstituted Phenolic Motif via Visible-Light-Mediated Group Transfer Radical Cyclization

Gamal A. I. Moustafa, Hiroshi Suizu, Hiroshi Aoyama, Masayoshi Arai, Shuji Akai, Takehiko Yoshimitsu

CHEMISTRY-AN ASIAN JOURNAL   9 ( 6 )   1506 - 1510   2014年6月

　詳細を見る

記述言語：英語   出版者・発行元：WILEY-V C H VERLAG GMBH  

A facile enantiospecific approach to (+)-ligudentatol (1) and (-)-ligudentatol (ent-1) is reported. The approach features the construction of a trisubstituted phenolic motif fused to a chiral aliphatic ring by a sequence of visible-light-mediated radical seleno transfer cyclization, bromination, concomitant selenoxide elimination-dehydrobromination, and demethoxycarbonylation, namely, a programmed aromatization. Biological evaluation of the enantiomers of ligudentatol obtained by the present route revealed for the first time their cytotoxicity towards various cancer cell lines.

DOI： 10.1002/asia.201400110

Web of Science

researchmap

Endeavors to Access Molecular Complexity: Strategic Use of Free Radicals in Natural Product Synthesis

Takehiko Yoshimitsu

CHEMICAL RECORD   14 ( 2 )   268 - 279   2014年4月

　詳細を見る

記述言語：英語   出版者・発行元：WILEY-V C H VERLAG GMBH  

Free radicals, which in the past were considered unruly chemical species, have become manageable and indispensable for synthetic organic chemistry. The unique nature of free radicals has allowed practitioners in organic synthesis to design flexible approaches to produce various materials ranging from small molecules to polymers. The present Personal Account describes the author's endeavors to create molecular complexity by the strategic use of free radicals, with an emphasis on the synthesis of bioactive natural products.

DOI： 10.1002/tcr.201300024

Web of Science

researchmap

A new route to platencin via decarboxylative radical cyclization

Gamal A. I. Moustafa, Yuki Saku, Hiroshi Aoyama, Takehiko Yoshimitsu

CHEMICAL COMMUNICATIONS   50 ( 99 )   15706 - 15709   2014年

　詳細を見る

記述言語：英語   出版者・発行元：ROYAL SOC CHEMISTRY  

A new approach to platencin, a potent antibiotic isolated from Streptomyces platensis, has been established. The highly congested tricyclic core of the natural product was successfully constructed by decarboxylative radical cyclization of an alkynyl silyl ester with Pb(OAc)(4) in the presence of pyridine in refluxing 1,4-dioxane. The key decarboxylation, which likely takes place via lead(IV) esterification followed by carbon-centered radical generation and subsequent capture of the radical with a triple bond, allows the rapid construction of the twisted polycyclic system.

DOI： 10.1039/c4cc07316a

Web of Science

researchmap

An integrated approach to the discovery of potent agelastatin A analogues for brain tumors: chemical synthesis and biological, physicochemical and CNS pharmacokinetic analyses 国際共著 国際誌

Zhimin Li, Daisuke Shigeoka, Thomas R. Caulfield, Takashi Kawachi, Yushi Qiu, Takuma Kamon, Masayoshi Arai, Han W. Tun, Takehiko Yoshimitsu

MEDCHEMCOMM   4 ( 7 )   1093 - 1098   2013年7月

　詳細を見る

記述言語：英語   出版者・発行元：ROYAL SOC CHEMISTRY  

(-)-Agelastatin A (AA), isolated from the coral sea axinellid sponge Agelas dendromorpha, has shown a high antineoplastic activity. We have synthesized eighteen AA analogues and analyzed their cytotoxicities towards three cancer cell lines. By the structure-activity relationship (SAR) study, we identified three novel analogues with higher or comparable cytotoxic activities to AA. They were subjected to chemoinformatic analysis, which revealed physicochemical properties favoring excellent central nervous system (CNS) penetration. CNS pharmacokinetic analysis in murine models validated the chemoinformatic prediction and revealed that these analogues indeed had better CNS penetration than AA. These novel potent AA analogues deserve further evaluation for therapeutic use against cancers, particularly primary and secondary brain tumors.

DOI： 10.1039/c3md00094j

Web of Science

researchmap

Formal synthesis of (-)-agelastatin A: an iron(II)-mediated cyclization strategy

Daisuke Shigeoka, Takuma Kamon, Takehiko Yoshimitsu

BEILSTEIN JOURNAL OF ORGANIC CHEMISTRY   9   860 - 865   2013年5月

　詳細を見る

記述言語：英語   出版者・発行元：BEILSTEIN-INSTITUT  

An iron(II)-mediated aminohalogenation of a cyclopentenyl N-tosyloxycarbamate provided new access to the key intermediate for the synthesis of (-)-agelastatin A (AA, 1), a potent antiproliferative alkaloid. The present synthetic endeavour offered an insight into the mechanism underlying the iron(II)-mediated aminohalogenation of N-tosyloxycarbamate, in which the radical properties of the N-iron intermediates in the redox states were operative.

DOI： 10.3762/bjoc.9.99

Web of Science

researchmap

Structure-activity relationships of hybrid annonaceous acetogenins: Powerful growth inhibitory effects of their connecting groups between heterocycle and hydrophobic carbon chain bearing THF ring on human cancer cell lines

Naoto Kojima, Tetsuya Fushimi, Takahiro Tatsukawa, Takehiko Yoshimitsu, Tetsuaki Tanaka, Takao Yamori, Shingo Dan, Hiroki Iwasaki, Masayuki Yamashita

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY   63   833 - 839   2013年5月

　詳細を見る

記述言語：英語   出版者・発行元：ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER  

Five novel hybrid molecules of annonaceous acetogenins and insecticides targeting mitochondrial complex I were synthesized and their growth inhibitory activities against 39 human cancer cell lines were investigated. It was revealed that the connecting group between the N-methylpyrazole part and the hydrophobic alkyl chain bearing the THF ring influenced their biological activities significantly. Amide-connected analog 2, in particular, showed selective and very potent activity (<10 nM) against some cancer cell lines. (C) 2013 Elsevier Masson SAS. All rights reserved.

DOI： 10.1016/j.ejmech.2013.03.009

Web of Science

researchmap

Potent Growth Inhibitory Activity of (±)-Platencin towards Multi-Drug-Resistant and Extensively Drug-Resistant Mycobacterium tuberculosis

Moustafa, G. A. I, Nojima, S, Yamano, Y, Aono, A, Arai, M, Mitarai, S, Tanaka, T, Yoshimitsu, T

Med. Chem. Commun.   4 ( 4 )   720 - 723   2013年4月

　詳細を見る

記述言語：英語  

DOI： 10.1039/c3md00016h

Web of Science

researchmap

Dichlorination of olefins with NCS/Ph3P

Yasumasa Kamada, Yuta Kitamura, Tetsuaki Tanaka, Takehiko Yoshimitsu

ORGANIC & BIOMOLECULAR CHEMISTRY   11 ( 10 )   1598 - 1601   2013年

　詳細を見る

記述言語：英語   出版者・発行元：ROYAL SOC CHEMISTRY  

A 2 : 1 mixture of NCS and Ph3P successfully promoted the anti-dichlorination of olefins to provide corresponding dichlorides, serving as a molecular chlorine surrogate generated in situ.

DOI： 10.1039/c3ob27345h

Web of Science

researchmap

Double C-H Functionalization in Sequential Order: Direct Synthesis of Polycyclic Compounds by a Palladium-Catalyzed C-H Alkenylation-Arylation Cascade

Hiroaki Ohno, Mutsumi Iuchi, Naoto Kojima, Takehiko Yoshimitsu, Nobutaka Fujii, Tetsuaki Tanaka

CHEMISTRY-A EUROPEAN JOURNAL   18 ( 17 )   5352 - 5360   2012年4月

　詳細を見る

記述言語：英語   出版者・発行元：WILEY-V C H VERLAG GMBH  

Palladium-catalyzed cascade C?H alkenylation and arylation provides convenient access to polycyclic aromatic compounds. Treatment of 3-bromoaniline derivatives bearing a bromocinnamyl group on the nitrogen atom with a catalytic amount of [Pd(OAc)2] and PCy3 center dot HBF4 in the presence of Cs2CO3 in dioxane affords naphthalene-fused indole derivatives in good yields. This double cyclization reaction is also applicable to heterocyclic substrates, giving fused indoles containing a heteroaromatic ring such as dibenzofuran, dibenzothiophene, carbazole, indole, or benzofuran through heterocyclic C-H arylation. When using a 2,6-unsubstituted aniline derivative, the first C-H arylation preferentially proceeds at the more hindered position of the aniline ring.

DOI： 10.1002/chem.201103819

Web of Science

researchmap

Pharmacokinetics of Agelastatin A in the central nervous system 国際共著 国際誌

Zhimin Li, Takuma Kamon, David A. Personett, Thomas Caulfield, John A. Copland, Takehiko Yoshimitsu, Han W. Tun

MEDCHEMCOMM   3 ( 2 )   233 - 237   2012年2月

　詳細を見る

記述言語：英語   出版者・発行元：ROYAL SOC CHEMISTRY  

Agelastatin A (AA) is an anti-neoplastic agent with anti-osteopontin (OPN) activity. Brain tumors often express OPN significantly. A comprehensive chemoinformatic analysis followed by in vivo pharmacokinetic evaluations in mice is performed. CNS penetration of AA is about 10%. AA should be further tested for activity against brain tumors.

DOI： 10.1039/c1md00240f

Web of Science

researchmap

Stereoselective α-Quaternization of 3-Methoxycycloalk-2-enones via 1,4-Diastereoinduction of Alkoxy Dienolates

Moustafa, G. A. I, Kamada, Y, Tanaka, T, Yoshimitsu, T

J. Org. Chem.   77 ( 2 )   1202 - 1207   2012年1月

　詳細を見る

記述言語：英語  

DOI： 10.1021/jo2022789

Web of Science

researchmap

Intramolecular iron(II)-catalyzed aminobromination of allyl N-tosyloxycarbamates

Takuma Kamon, Daisuke Shigeoka, Tetsuaki Tanaka, Takehiko Yoshimitsu

ORGANIC & BIOMOLECULAR CHEMISTRY   10 ( 12 )   2363 - 2365   2012年

　詳細を見る

記述言語：英語   出版者・発行元：ROYAL SOC CHEMISTRY  

Allyl N-tosyloxycarbamates are found to be catalytically transformed into beta-brominated oxazolidinones with FeBr2/n-Bu4NBr in t-BuOH.

DOI： 10.1039/c2ob07190h

Web of Science

researchmap

Stereoconvergent route to chiral cyclohexenone building blocks: formal synthesis of (-)-dysidiolide

Gamal A. I. Moustafa, Yasumasa Kamada, Tetsuaki Tanaka, Takehiko Yoshimitsu

ORGANIC & BIOMOLECULAR CHEMISTRY   10 ( 43 )   8609 - 8615   2012年

　詳細を見る

記述言語：英語   出版者・発行元：ROYAL SOC CHEMISTRY  

A stereoconvergent access to chiral carbocyclic building blocks is reported. 6-(3'-Hydroxy-4'-methylpent-4'-enyl)-3-methoxy cyclohex-2-enone (1) that consists of four stereoisomers, i.e., racemic ca. 1:1 diastereomers, is converted to enantiomerically pure carbocycles through a combination of regioselective catalytic asymmetric reduction and alkylative remote stereoinduction. The present stereoconvergent strategy has allowed the formal synthesis of bioactive (-)-dysidiolide.

DOI： 10.1039/c2ob26532j

Web of Science

researchmap

Design and synthesis of C35-fluorinated solamins and their growth inhibitory activities against human cancer cell lines

Naoto Kojima, Yuki Suga, Hiromi Hayashi, Takao Yamori, Takehiko Yoshimitsu, Tetsuaki Tanaka

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS   21 ( 19 )   5745 - 5749   2011年10月

　詳細を見る

記述言語：英語   出版者・発行元：PERGAMON-ELSEVIER SCIENCE LTD  

The convergent synthesis of C35-fluorinated analogues of solamin, a mono-THF Annonaceous acetogenin, has been achieved by the Sonogashira coupling of the THF ring fragment and the fluorinated gamma-lactone fragment. It was revealed that the number of fluorine atoms on the gamma-lactone moiety affects the growth inhibitory activities against human cancer cell lines. (C) 2011 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.bmcl.2011.08.011

Web of Science

researchmap

Total Synthesis of (±)-Platencin

Yoshimitsu, T, Nojima, S, Hashimoto, M, Tanaka, T

Org. Lett.   13 ( 14 )   3698 - 3701   2011年7月

　詳細を見る

記述言語：英語  

DOI： 10.1021/ol2013439

Web of Science

researchmap

Total Synthesis of (±)-Kainic Acid: A Photochemical C–H Carbamoylation Approach

Kamon, T, Irifune, Y, Tanaka, T, Yoshimitsu, T

Org. Lett.   13 ( 10 )   2674 - 2677   2011年5月

　詳細を見る

記述言語：英語  

DOI： 10.1021/ol200772f

Web of Science

researchmap

Asymmetric Total Synthesis of (+)-Danicalipin A

Takehiko Yoshimitsu, Ryo Nakatani, Akihiro Kobayashi, Tetsuaki Tanaka

ORGANIC LETTERS   13 ( 5 )   908 - 911   2011年3月

　詳細を見る

記述言語：英語   出版者・発行元：AMER CHEMICAL SOC  

A convergent asymmetric total synthesis of (+)-danicalipin A is accomplished, in which two chlorinated fragments are stereoselectively joined by 1,3-dipolar coupling, leading to the confirmation of the absolute configuration of the natural product.

DOI： 10.1021/ol1029518

Web of Science

researchmap

Convergent synthesis of fluorescence-labeled probes of Annonaceous acetogenins and visualization of their cell distribution

Naoto Kojima, Takekuni Morioka, Daisuke Urabe, Masahiro Yano, Yuki Suga, Naoyoshi Maezaki, Ayako Ohashi-Kobayashi, Yasuyuki Fujimoto, Masatomo Maeda, Takao Yamori, Takehiko Yoshimitsu, Tetsuaki Tanaka

BIOORGANIC & MEDICINAL CHEMISTRY   18 ( 24 )   8630 - 8641   2010年12月

　詳細を見る

記述言語：英語   出版者・発行元：PERGAMON-ELSEVIER SCIENCE LTD  

The convergent synthesis of fluorescence-labeled solamin, an antitumor Annonaceous acetogenin, was accomplished by two asymmetric alkynylations of 2,5-diformyl tetrahydrofuran with an alkyne tagged with fluorescent groups and another alkyne with an alpha,beta-unsaturated gamma-lactone. Assay for the growth inhibitory activity against human cancer cell lines revealed that the probe with the fluorescent groups at the end of the hydrocarbon chain may have the same mode of action as natural acetogenins. The merged fluorescence of dansyl-labeled solamin and MitoTracker Red suggests that Annonaceous acetogenins localize in the mitochondria. (C) 2010 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.bmc.2010.10.004

Web of Science

researchmap

Asymmetric Total Synthesis of (+)-Hexachlorosulfolipid, a Cytotoxin Isolated from Adriatic Mussels

Takehiko Yoshimitsu, Naoya Fukumoto, Ryo Nakatani, Naoto Kojima, Tetsuaki Tanaka

JOURNAL OF ORGANIC CHEMISTRY   75 ( 16 )   5425 - 5437   2010年8月

　詳細を見る

記述言語：英語   出版者・発行元：AMER CHEMICAL SOC  

The enantioselective total synthesis of (+)-hexachlorosulfolipid, a cytotoxin found in the Adriatic mussel Mytilus galloprovincialis, is described. The unique chlorinated hydrocarbon motif of the lipid is successfully furnished by a series of dichlorination reactions of chiral epoxides with chlorophosphonium reagent generated in situ from Ph(3)P/NCS. The present total synthesis has allowed the confirmation of the absolute configuration of the natural cytotoxic (+)-hexachlorosulfolipid originally proposed by Fattorusso, Ciminiello, and co-workers.

DOI： 10.1021/jo100534d

Web of Science

researchmap

Studies of the Asymmetric Total Synthesis of Clavilactone D by the 'Lariat' Cyclization Strategy

Takehiko Yoshimitsu, Shoji Nojima, Masashi Hashimoto, Koji Tsukamoto, Tetsuaki Tanaka

SYNTHESIS-STUTTGART   17 ( 17 )   2963 - 2969   2009年9月

　詳細を見る

記述言語：英語   出版者・発行元：GEORG THIEME VERLAG KG  

A route to the core structure of clavilactone D, a new member of the tyrosine kinase inhibitors, is reported. The route employs sequential cyclization initiated by iodo etherification followed by Friedel-Crafts cyclization to furnish a polycyclic lactone fused with an aromatic ring, which is readily transformed into the proposed clavilactone scaffold.

DOI： 10.1055/s-0029-1216909

Web of Science

researchmap

Total Synthesis of the β-Catenin Inhibitor, (－)-Agelastatin A: A Second-Generation Approach Based on Radical Aminobromination

T.Yoshimitsu, T. Ino, N. Futamura, T. Kamon, T. Tanaka

Org. Lett.   11 ( 15 )   3402 - 3405   2009年8月

　詳細を見る

記述言語：英語  

DOI： 10.1021/ol9012684

Web of Science

researchmap

SYNTHESIS OF CHAETOMELLIC ANHYDRIDE A, A POTENT INHIBITOR OF RAS PROTEIN FARNESYLTRANSFERASE

Takehiko Yoshimitsu, Yoshimasa Arano, Tomohiro Kaji, Tatsunori Ino, Hiroto Nagaoka, Tetsuaki Tanaka

HETEROCYCLES   77 ( 1 )   179 - 186   2009年1月

　詳細を見る

記述言語：英語   出版者・発行元：PERGAMON-ELSEVIER SCIENCE LTD  

Chaetomellic anhydride A, a potent inhibitor of Ras protein farnesyltransferase, was synthesized in 61% yield over four steps from methyl propionate. The synthesis features palladium-catalyzed carboxylation reaction under Cacchi conditions, efficiently incorporating carbon monoxide generated in situ from acetic formic anhydride into beta-carbomethoxyalkenyl triflate, and giving rise to the maleic anhydride motif of chaetomellic anhydride A. Noteworthy is the remarkable reactivity of the carboxylation reaction that takes place at room temperature despite the fact that common palladium-catalyzed carboxylations generally require rather harsh conditions. The scope of the method is also presented.

DOI： 10.3987/COM-08-S(F)16

Web of Science

researchmap

Enantiocontrolled Synthesis of Polychlorinated Hydrocarbon Motifs: A Nucleophilic Multiple Chlorination Process Revisited

Takehiko Yoshimitsu, Naoya Fukumoto, Tetsuaki Tanaka

JOURNAL OF ORGANIC CHEMISTRY   74 ( 2 )   696 - 702   2009年1月

　詳細を見る

記述言語：英語   出版者・発行元：AMER CHEMICAL SOC  

Polychlorinated hydrocarbon motifs have been synthesized in enantiomerically pure forms by means of nucleophilic multiple chlorinations of chiral epoxides, which stereospecifically incorporate halogen atoms into oxygenated molecular scaffolds. The present study demonstrates the scope of the N-chlorosuccinimide (NCS)/organophosphine reagent system that forms multiple sp(3)C-Cl bonds in a regularly repeating pattern, with proper stereochemical configurations and evaluates its applicability to various epoxides having elaborate structures. It is noteworthy that tetrachlorinated motifs are produced in one step from bisepoxides by using NCS/Ph(3)P. Furthermore, Ph(2)PCl used in combination with NCS has been found to serve as a potentially useful alternative to NCS/Ph(3)P, especially for promoting dichlorination reactions of alkenyl-substituted epoxides.

DOI： 10.1021/jo802093d

Web of Science

researchmap

Total Synthesis of (-)-Agelastatin A

Takehiko Yoshimitsu, Tatsunori Ino, Tetsuaki Tanaka

ORGANIC LETTERS   10 ( 23 )   5457 - 5460   2008年12月

　詳細を見る

記述言語：英語   出版者・発行元：AMER CHEMICAL SOC  

A new route to (-)-agelastatin A is reported. The requisite nitrogen functionalities of the agelastatin core have been installed by intramolecular aziridination of an azidoformate and subsequent regioselective azidation, leading to net trans-diamination of the double bond. The present synthesis also demonstrates two new protocols for the preparation of an imidazolidinone hemiaminal motif from an oxazolidinone intermediate which comprise sequential N-tert-butoxycarbonylation, urea formation, hydrolysis, and oxidative cyclization, and direct aminolysis and subsequent oxidative cyclization.

DOI： 10.1021/ol802225g

Web of Science

researchmap

Synthesis of (±)-Aphanorphine: a New Approach to Tricyclic 3-Benzazepine Scaffold Using Two Radical C-C Bond-Forming Reactions

Yoshimitsu, T, Atsumi, C, Iimori, E, Nagaoka, H, Tanaka, T

Tetrahedron Lett.   49 ( 29-30 )   4473 - 4475   2008年7月

　詳細を見る

記述言語：英語  

DOI： 10.1016/j.tetlet.2008.05.058

Web of Science

researchmap

フリーラジカルが拓くヘテロ分子骨格形成の新手法

好光健彦, 田中徹明

生産と技術   90 ( 1 )   99 - 101   2008年

　詳細を見る

記述言語：日本語   出版者・発行元：生産技術振興協会  

CiNii Article

CiNii Books

researchmap

Radical fixation of functionalized carbon resources: alpha-sp(3)C-H carbamoylation of tertiary amines with aryl isocyanates

Takehiko Yoshimitsu, Kenichi Matsuda, Hiroto Nagaoka, Koji Tsukamoto, Tetsuaki Tanaka

ORGANIC LETTERS   9 ( 24 )   5115 - 5118   2007年11月

　詳細を見る

記述言語：英語   出版者・発行元：AMER CHEMICAL SOC  

A new carbamoylation of tertiary amines is reported. This rare C-H transformation features the direct generation of alpha-aminoalkyl radicals from tertiary amines, followed by the addition of the resultant nucleophilic radicals to isocyanates, enabling unique access to N,N-dlalkylated amino acid derivatives. The authors put forward a mechanistic proposal that is based on the isolation of borinamides produced by capturing nitrogen radical intermediates with Et3B. The present transformation provides a novel one-step process for producing mepivacaine, a clinically important local anesthetic, from readily available materials.

DOI： 10.1021/ol7023295

Web of Science

researchmap

フリーラジカルによるα-ヘテロ原子置換sp3炭素―水素結合の新変換法の発見と進展

好光健彦

ファルマシア‐最前線‐   43 ( 3 )   219 - 223   2007年

　詳細を見る

記述言語：日本語   出版者・発行元：公益社団法人日本薬学会  

CiNii Article

CiNii Books

researchmap

高反応性ラジカル種が誘起する炭素-炭素および炭素-水素結合変換と生物活性物質合成への活用

好光健彦, 長岡博人, 田中徹明

有機合成化学協会誌   65   665 - 676   2007年

　詳細を見る

researchmap

解説「Barton反応」

好光健彦

有機合成化学協会誌   65   727 - 727   2007年

　詳細を見る

researchmap

現代化学 増刊43 最新有機合成化学 ヘテロ原子・遷移金属化合物を用いる合成, 奈良坂紘一,岩澤伸治編, 東京化学同人, B5, 220頁, 4,410円

好光 健彦

ファルマシア   41 ( 8 )   740 - 740   2005年8月

　詳細を見る

記述言語：日本語   出版者・発行元：公益社団法人日本薬学会  

CiNii Article

CiNii Books

researchmap

Radical hydroxyalkylation of C-H bond adjacent to nitrogen of tertiary amides, ureas, and amines

T Yoshimitsu, Y Arano, H Nagaoka

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY   127 ( 33 )   11610 - 11611   2005年8月

　詳細を見る

記述言語：英語   出版者・発行元：AMER CHEMICAL SOC  

DOI： 10.1021/ja053855q

Web of Science

researchmap

Radical alpha-C-H hydroxyalkylation of ethers and acetal

T Yoshimitsu, Y Arano, H Nagaoka

JOURNAL OF ORGANIC CHEMISTRY   70 ( 6 )   2342 - 2345   2005年3月

　詳細を見る

記述言語：英語   出版者・発行元：AMER CHEMICAL SOC  

Ethers and an acetal were found to undergo direct intermolecular addition to aldehydes under the Et3B/air conditions. This study presents a very unique and simple means for the radical alpha-C-H hydroxyalkylation of oxygen-containing compounds.

DOI： 10.1021/jo048248k

Web of Science

researchmap

Studies on the total synthesis of (-)-CP-263,114

T Yoshimitsu, S Sasaki, Y Arano, H Nagaoka

JOURNAL OF ORGANIC CHEMISTRY   69 ( 26 )   9262 - 9268   2004年12月

　詳細を見る

記述言語：英語   掲載種別：書評論文，書評，文献紹介等   出版者・発行元：AMER CHEMICAL SOC  

Alkoxyl radicals have a wide range of applications in organic synthesis due to their remarkable chemical properties in molecular transformation. The present study shows two types of alkoxyl radicals (primary vs tertiary) to selectively undergo dehydrogenation and beta-scission to give rise to key structural elements of (-)-CP-263,114 (1). By alkoxyl radical transformation followed by installation of the C19-C25 (CP numbering) side chain and the bridged bisacetal unit, the functionalized CP precursor 2 was obtained.

DOI： 10.1021/jo048681u

Web of Science

researchmap

Total synthesis of (+)-muconin

T Yoshimitsu, T Makino, H Nagaoka

JOURNAL OF ORGANIC CHEMISTRY   69 ( 6 )   1993 - 1998   2004年3月

　詳細を見る

記述言語：英語   出版者・発行元：AMER CHEMICAL SOC  

(+)-Muconin (1), isolated from the leaves of Rollinia mucosa (Jacq.) Baill. (Annonaceae), is a sequential THF/THP-possessing acetogenin that exhibits potent and selective in vitro cytotoxicity toward pancreatic and breast tumor cell lines. In this study, a new route was established for obtaining (+)-muconin (1) starting with (-)-muricatacin (2), a compound recently synthesized via the novel alpha-C-H hydroxyalkylation and alpha'-C-H oxidation of tetrahydrofuran.

DOI： 10.1021/jo0303721

Web of Science

researchmap

Synthesis of (-)-muricatacin via alpha- and alpha '-C-H bond functionalization of tetrahydrofuran

T Yoshimitsu, T Makino, H Nagaoka

JOURNAL OF ORGANIC CHEMISTRY   68 ( 19 )   7548 - 7550   2003年9月

　詳細を見る

記述言語：英語   出版者・発行元：AMER CHEMICAL SOC  

(-)-Muricatacin, a potent cytotoxic (4R,5R)-5-hydroxyheptadecan-4-olide, has been synthesized through alpha-C-H hydroxyalkylation and alpha'-C-H oxidation of tetrahydrofaran. This study presents a novel method for C-H bond functionalization as a means for preparing gamma-(hydroxyalkyl)-gamma-butyrolactones.

DOI： 10.1021/jo0301696

Web of Science

researchmap

Hydroxyalkylation of alpha-C-H bonds of tetrahydrofuran with aldehydes in the presence of triethylborane and tert-butyl hydroperoxide

T Yoshimitsu, Y Arano, H Nagaoka

JOURNAL OF ORGANIC CHEMISTRY   68 ( 2 )   625 - 627   2003年1月

　詳細を見る

記述言語：英語   出版者・発行元：AMER CHEMICAL SOC  

The alpha-hydroxyalkylation of tetrahydrofuran with aldehydes via radical C-H abstraction was conducted using triethylborane in the presence of tert-butyl hydroperoxide. This study presents a rare instance of direct intermolecular radical addition of unactivated cyclic ether to aldehydes.

DOI： 10.1021/jo020590e

Web of Science

researchmap

Synthesis of the CD ring system of paclitaxel by atom-transfer radical annulation reaction

T Yoshimitsu, H Nakajima, H Nagaoka

TETRAHEDRON LETTERS   43 ( 47 )   8587 - 8590   2002年11月

　詳細を見る

記述言語：英語   出版者・発行元：PERGAMON-ELSEVIER SCIENCE LTD  

Atom-transfer radical annulation of diene derived from D-glucose under Kharasch conditions provided access to the fully functionalized CD ring system of paclitaxel. (C) 2002 Elsevier Science Ltd. All rights reserved.

DOI： 10.1016/S0040-4039(02)02058-0

Web of Science

researchmap

Asymmetric synthesis of the core structure of (-)-CP-263,114

T Yoshimitsu, S Yanagisawa, H Nagaoka

ORGANIC LETTERS   2 ( 23 )   3751 - 3754   2000年11月

　詳細を見る

記述言語：英語   出版者・発行元：AMER CHEMICAL SOC  

[GRAPHICS]
The enantioselective construction of a fully functionalized core structure of (-)-CP-263,114 (1) containing most of the required functionality for total synthesis, was conducted through sequential radical fragmentation-reductive olefination.

DOI： 10.1021/ol000290o

Web of Science

researchmap

New Route to the Synthesis of the Illudane Skeleton by Michael–Michael-Elimination Reaction

Tokuzaki, K, Kanemitsu, Y, Yoshimitsu, T, Nagaoka, H

Tetrahedron Lett.   41 ( 31 )   5923 - 5926   2000年7月

　詳細を見る

記述言語：英語  

DOI： 10.1016/S0040-4039(00)00974-6

Web of Science

researchmap

New method for the synthesis of alpha-substituted tetrahydrofuran-2-methanols through diastereoselective addition of THF to aldehydes mediated by Et3B in the presence of air

T Yoshimitsu, M Tsunoda, H Nagaoka

CHEMICAL COMMUNICATIONS   ( 17 )   1745 - 1746   1999年9月

　詳細を見る

記述言語：英語   出版者・発行元：ROYAL SOC CHEMISTRY  

The tetrahydrofuranyl radical, generated from THF with Et3B in the presence of air, was found to react with aldehydes threo-selectively to afford alpha-substituted tetrahydrofuran-2-methanols, the common structural motifs of biologically active acetogenin polyketides, in moderate yields.

DOI： 10.1039/A904745J

Web of Science

researchmap

An approach to the synthesis of CP-263,114: complementary routes to the bicyclic ring system via two kinds of fragmentation reaction

T Yoshimitsu, M Yanagiya, H Nagaoka

TETRAHEDRON LETTERS   40 ( 28 )   5215 - 5218   1999年7月

　詳細を見る

記述言語：英語   出版者・発行元：PERGAMON-ELSEVIER SCIENCE LTD  

Two complementary methods for the construction of the ring system of CP-263,114 (1), one relying on the Grob fragmentation reaction and the other on a sequential photolytic alkoxy radical fragmentation-reduction, are described. (C) 1999 Elsevier Science Ltd. All rights reserved.

DOI： 10.1016/S0040-4039(99)00941-7

Web of Science

researchmap

A new synthetic route for construction of the core of zaragozic acids

H Koshimizu, T Baba, T Yoshimitsu, H Nagaoka

TETRAHEDRON LETTERS   40 ( 14 )   2777 - 2780   1999年4月

　詳細を見る

記述言語：英語   出版者・発行元：PERGAMON-ELSEVIER SCIENCE LTD  

A new synthetic route for construction of the core moiety of zaragozic acids from 2,5-furandimethanol (2) is described. This synthesis involves highly stereocontrolled transformation of 2 into 7-oxabicyclo[2.2.1] heptane derivative 13, and the Grob fragmentation-reduction-iodo acetalization reaction (one-pot process) of 13 as a key step to give 16. (C) 1999 Elsevier Science Ltd. All rights reserved.

DOI： 10.1016/S0040-4039(99)00256-7

Web of Science

researchmap

Application of newly developed anti-selective aldol methodology: Synthesis of C6-C13 and C19-C28 fragments of miyakolide

T Yoshimitsu, JJ Song, GQ Wang, S Masamune

JOURNAL OF ORGANIC CHEMISTRY   62 ( 26 )   8978 - 8979   1997年12月

　詳細を見る

記述言語：英語   掲載種別：速報，短報，研究ノート等（学術雑誌）   出版者・発行元：AMER CHEMICAL SOC  

DOI： 10.1021/jo971863m

Web of Science

researchmap