Article
Chemistry, Organic
Shinya Tabata, Mai Minoshima, Akihiro Kobayashi, Takamitsu Hosoya, Suguru Yoshida
Summary: Migrative thioamination of aryne intermediates using o-iodoaryl triflates and sulfilimines leads to the formation of highly functionalized o-thioaminated diaryl sulfides. The ring expansion of cyclic sulfilimines enables the synthesis of eight- and nine-membered organosulfur compounds from dibenzothiophene- and thianthrene-type sulfilimines, respectively.
Article
Chemistry, Multidisciplinary
Thomas M. Haas, Stefan Wiesler, Tobias Duerr-Mayer, Alexander Ripp, Paraskevi Fouka, Danye Qiu, Henning J. Jessen
Summary: Condensed phosphates are important molecules in biochemistry with various applications. Research into their reactivity and potential as arynophiles for oligophosphorylation reactions is essential for developing new functionalization methods. The aryne phosphate reaction enables efficient synthesis of a broad spectrum of arylated products, demonstrating great synthetic potential in diverse areas.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Organic
Y. N. Sambasiva Rao, Palash Ghosh, Prathama S. Mainkar, Srivari Chandrasekhar
Summary: An efficient and metal-free strategy has been developed for the synthesis of spiro-fused indanolactones/lactams via the reaction of arynes with alpha-chloroacetyl lactones/lactams. This strategy allows for the access to spiroindanone derivatives through aryne insertion/spirocyclization.
Article
Chemistry, Multidisciplinary
Marcel Buerger, Nadine Ehrhardt, Thomas Barber, Liam T. Ball, Jan C. Namyslo, Peter G. Jones, Daniel B. Werz
Summary: A phosphine-catalyzed oligomerization of arynes using selenocyanates has been developed to access alpha, omega-bisfunctionalized oligo(ortho-arylenes). The use of JohnPhos as a bulky phosphine catalyst is crucial for this reaction to occur. Various optimized conditions have been established to predominantly form dimers, but also higher oligomers, up to octamers, depending on the electronic properties of the electrophilic reaction partner. Mechanistic studies show that the cascade reaction starts with cyanide attack and rules out aryne insertion into n-mers leading to (n+1)-mers.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Chemistry, Inorganic & Nuclear
Hong Wang, Changli Zhang, Zhiyong Jiang, Li Xu, Zhipeng Liu
Summary: In this study, phenothiazine-fused boron complexes were identified as promising scaffolds for ratiometric fluorescent hypochlorite probes. The synthesized complexes demonstrated ultrafast and ratiometric absorption/fluorescence changes for hypochlorite. Additionally, an endoplasmic reticulum-targeting probe was developed and showed excellent real-time imaging ability for both endogenous and exogenous hypochlorite in living cells.
DALTON TRANSACTIONS
(2023)
Review
Chemistry, Multidisciplinary
Jiarong Shi, Lianggui Li, Yang Li
Summary: Arynes are highly active organic intermediates used in the rapid synthesis of substituted arenes, with o-silylaryl triflates being the most frequently employed precursors. The resurgence in aryne chemistry over the past 20 years is largely attributed to the widespread use of Kobayashi's method, which involves fluoride-induced removal of the TMS group with concomitant departure of its ortho OTf group. This review provides an overview of the history, achievements, and applications of Kobayashi's method in the synthesis of natural products, bioactive molecules, and polycyclic aromatic hydrocarbons.
Article
Multidisciplinary Sciences
Jason V. Chari, Katie A. Spence, Robert B. Susick, Neil K. Garg
Summary: The study presents a versatile platform for on-the-complex annulation reactions using transient aryne intermediates to access pi-extended polypyridyl complexes, providing an effective strategy for annulating organometallic complexes and accessing complex metal-ligand scaffolds.
NATURE COMMUNICATIONS
(2021)
Article
Chemistry, Organic
Jiajing Tan, Xiaoying Feng, Rong Fan, Zhe Zhuang, Yifeng Guo
Summary: Organosulfur compounds are widely present in various fields and their efficient assembly through S(IV) intermediates has become a focus in organic synthesis. This account systematically reviews the efforts made by our research group in aryne-induced, sulfonium-zwitterion based synthetic methodologies, including sigmatropic rearrangements, ring opening of cyclic sulfides, and selective S-arylation of thiooxindoles. These protocols offer mild conditions, avoid the use of transition metals, and enable the access to diverse organosulfur compounds.
Article
Chemistry, Multidisciplinary
Nandikolla Krishna Chaitanya, Y. N. Sambasiva Rao, Venkata Surya Kumar Choutipalli, Prathama S. Mainkar, Venkatesan Subramanian, Srivari Chandrasekhar
Summary: Cyclic and acyclic vinyl-substituted β-keto/enol carbonyl substrates react with arynes to yield differentially substituted naphthyl carbocycles. The ring size of the cyclic β-keto/enol esters plays a significant role in product formation.
CHEMICAL COMMUNICATIONS
(2022)
Article
Chemistry, Organic
Yaling Xu, Jieyi Gao, Caihong Wang, Yunfei Ma, Jun Zhou, Ge Wu
Summary: The copper-catalyzed oxidative aminophosphorothiolation of maleimides with secondary alkylamines and diethylphosphorodithioate has been established, providing a concise pathway to access structurally diverse beta-amino vinyl phosphorodithioates. The utility of this protocol is further highlighted in late-stage vinylphosphorothiolation of amine-containing drug fragments.
ORGANIC CHEMISTRY FRONTIERS
(2021)
Article
Chemistry, Multidisciplinary
Supriya Halder, Sourav Mandal, Abhishek Kundu, Baishanal Mandal, Debashis Adhikari
Summary: Here, we describe the highly reducing nature of the anion of benzo[b]phenothiazine upon excitation by visible light. This molecule shows extreme reducing power and can promote reductive cleavage reactions at a low potential. This property has been demonstrated by the successful synthesis of isoindolinone and oxindole molecules through the reductive cleavage of aryl chloride substrates.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Multidisciplinary
Eva Kran, Christian Muck-Lichtenfeld, Constantin G. Daniliuc, Armido Studer
Summary: In this study, the reaction of in situ generated arynes with stannylated imines to provide ortho-stannyl-aniline derivatives was reported, with good yields and regioselectivities. The product anilines are valuable starting materials for follow-up chemistry due to the rich chemistry offered by the trimethylstannyl moiety.
CHEMISTRY-A EUROPEAN JOURNAL
(2021)
Article
Chemistry, Multidisciplinary
Katie A. Spence, Jason Chari, Mattia Di Niro, Robert B. Susick, Narcisse Ukwitegetse, Peter Djurovich, Mark E. Thompson, Neil K. Garg
Summary: This paper reports a method for accessing pi-extended polycyclic aromatic hydrocarbons (PAHs) through the annulation of heterocyclic building blocks. The utility of this method in the synthesis and study of organic materials is demonstrated.
Article
Chemistry, Organic
Avisikta Sinha, Mangalampalli Ravikanth
Summary: Novel nonaromatic stable phenothiazine-embedded porphyrinoids were successfully synthesized, exhibiting distinct absorption bands in the visible-near-infrared region and electron-rich nature, with a twisted conformation in the macrocycle as observed in the crystal structure.
Article
Chemistry, Multidisciplinary
Thomas Sephton, Anastasios Charitou, Cristina Trujillo, Jonathan M. Large, Sam Butterworth, Michael F. Greaney
Summary: This study found that benzyne can be used to activate anilines and set up aryl transfer reactions in a single step, establishing a metal-free route to valuable biaryl products.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Biochemistry & Molecular Biology
Satoshi Inouye, Mitsuhiro Nakamura, Takamitsu Hosoya
Summary: This study successfully demonstrates the enzymatic conversion of dCTZ to CTZ using NAD(P)H:FMN oxidoreductase, providing a new synthetic pathway for CTZ. Furthermore, the concentration of dCTZ can be determined by measuring the luminescence activity using CTZ-utilizing luciferases coupled with the FRase-NADH reaction.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Chemistry, Multidisciplinary
Rika Idogawa, Akihiro Kobayashi, Youngchan Kim, Ken Shimomori, Takamitsu Hosoya, Suguru Yoshida
Summary: An efficient method for sequential C-F transformations of o-hydrosilyl-substituted benzotrifluorides was developed, allowing for the synthesis of a wide variety of organofluorine compounds through successive reactions. Key to the success was the hydride reduction of o-fluorosilyl-substituted difluoromethylenes, enabling further C-F transformations.
CHEMICAL COMMUNICATIONS
(2022)
Article
Chemistry, Multidisciplinary
Jumpei Taguchi, Kota Kimura, Kazunobu Igawa, Katsuhiko Tomooka, Takamitsu Hosoya
Summary: The generation of 3-azidoarynes from o-iodoaryl triflate-type precursors was achieved using a silylmethyl Grignard reagent as the activator. The azido group controls the regioselectivity of the reaction and can be further transformed into different nitrogen-containing compounds.
Article
Pharmacology & Pharmacy
Takayoshi Nakaoka, Ken-ichi Kaneko, Satsuki Irie, Aya Mawatari, Ami Igesaka, Yuta Uetake, Hidenori Ochiai, Takashi Niwa, Emi Yamano, Yasuhiro Wada, Masaaki Tanaka, Kohei Kotani, Hideki Kawahata, Joji Kawabe, Yukio Miki, Hisashi Doi, Takamitsu Hosoya, Maeda Kazuya, Hiroyuki Kusuhara, Yuichi Sugiyama, Yasuyoshi Watanabe
Summary: Uptake and efflux transporters play crucial roles in drug disposition. PET imaging is a useful tool for directly assessing drug transporter activity. A synthetic method for [18F]PTV, a PET probe for hepatobiliary transport, was developed. Rifampicin pretreatment significantly inhibited hepatic concentration and biliary excretion of the probe and decreased hepatic uptake clearance and canalicular efflux clearance. These results demonstrate the usefulness of [18F]PTV for investigating hepatobiliary transporters in humans.
DRUG METABOLISM AND PHARMACOKINETICS
(2022)
Article
Chemistry, Medicinal
Yuka Miyazaki, Masaki Kikuchi, Koji Umezawa, Aurelie Descamps, Daichi Nakamura, Gaku Furuie, Tomoe Sumida, Kanako Saito, Ninako Kimura, Takashi Niwa, Yuto Sumida, Takashi Umehara, Takamitsu Hosoya, Isao Kii
Summary: The study investigates DYRK1A's folding intermediate-selective inhibition and introduces a novel small molecule inhibitor termed dp-FINDY, expanding chemical options for kinase inhibitor design.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Organic
Hinano Takemura, Gaku Orimoto, Akihiro Kobayashi, Takamitsu Hosoya, Suguru Yoshida
Summary: This study discloses assembling methods using 2-azidoacrylamides with a nucleophilic amino group. Divergent transformations of the amine-type trivalent platform resulted in a wide range of 2-azidoacrylamides involving a fluorosulfonyl group. Consecutive click conjugations, including triazole formation, thiol-ene-type 1,4-addition, and SuFEx reactions, efficiently assembled easily available simple modules.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Satoshi Inouye, Mitsuhiro Nakamura, Takamitsu Hosoya
Summary: This study investigated the degradation process of CTZ-OOH in aequorin and found that CTM was the major product after acid treatment, with no significant luminescence. 4HPPA and 4HPAA were identified as the counterparts of CTM in CTZ-OOH using mass spectrometry. The luminescence reaction of aequorin with Ca2+ showed similar amounts of 4HPPA and 4HPAA, suggesting that CTM is formed through dioxetanone anion rather than hydrolysis from CTMD.
PHOTOCHEMISTRY AND PHOTOBIOLOGY
(2022)
Article
Physics, Multidisciplinary
Tomonori Fukuchi, Takashi Niwa, Takamitsu Hosoya, Yasuyoshi Watanabe
Summary: In studying the chemical origin of life, researchers found that under certain conditions, the probability of producing glycine through C-14 beta-decay can reach 81%. Even with a lower dissociation energy, there is still an expected probability of producing approximately 32% glycine.
JOURNAL OF THE PHYSICAL SOCIETY OF JAPAN
(2022)
Article
Chemistry, Organic
Akira Nagai, Akihiro Kobayashi, Yuki Sakata, Yasunori Minami, Keisuke Uchida, Takamitsu Hosoya, Suguru Yoshida
Summary: A new method for synthesizing multifunctionalized arenes from simple phenols using aryne intermediates is described. The aryne precursors were prepared from phenols through various transformations, and the highly functionalized aryne intermediates were used to synthesize multisubstituted arenes.
SYNTHESIS-STUTTGART
(2022)
Article
Chemistry, Multidisciplinary
Akihiro Kobayashi, Tsubasa Matsuzawa, Takamitsu Hosoya, Suguru Yoshida
Summary: The interrupted Pummerer reaction of alkynyl sulfoxides with phenols is reported, leading to the efficient synthesis of various benz[b]furans through the unexplored electrophilic activation of the electron-deficient alkynyl sulfinyl group. Utilizing readily available alkynes, thiosulfonates, and phenols, we successfully prepared functionalized benz[b]furans.
Article
Chemistry, Multidisciplinary
Zhouen Zhang, Takashi Niwa, Kenji Watanabe, Takamitsu Hosoya
Summary: In this study, a two-phase radiosynthetic method for the ipso-C-11-cyanation of aryl fluorides was developed, using nickel-mediated C-F bond activation. A practical protocol was established that does not require a glovebox, making it applicable for general PET centers. This method enabled the efficient synthesis of diverse [C-11]aryl nitriles, including pharmaceutical drugs. Stoichiometric reactions and theoretical studies demonstrated the significant promotion effect of lithium chloride on the oxidative addition, facilitating rapid C-11-cyanation.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Takashi Niwa, Tsuyoshi Tahara, Charles E. Chase, Francis G. Fang, Takayoshi Nakaoka, Satsuki Irie, Emi Hayashinaka, Yasuhiro Wada, Hidefumi Mukai, Kenkichi Masutomi, Yasuyoshi Watanabe, Yilong Cui, Takamitsu Hosoya
Summary: This study reports the successful 11C-radiolabeling of eribulin, an approved anticancer drug, which enables the quantitative measurement of eribulin migration into tumor tissue. The optimized synthetic method provides a reproducible way to produce [35-11C]eribulin with high radiochemical purity and molar activity. PET imaging using mice shows specific accumulation of [35-11C]eribulin in tumors without significant metabolic changes.
BULLETIN OF THE CHEMICAL SOCIETY OF JAPAN
(2023)
Article
Psychiatry
Manon Dubol, Jana Immenschuh, My Jonasson, Kayo Takahashi, Takashi Niwa, Takamitsu Hosoya, Sara Roslin, Johan Wikstrom, Gunnar Antoni, Yasuyoshi Watanabe, Mark Lubberink, Anat Biegon, Inger Sundstrom-Poromaa, Erika Comasco
Summary: The study investigated the availability of aromatase in healthy women before and after nicotine exposure. The findings suggest that nicotine acutely decreases aromatase availability in the thalamic area, indicating a potential mechanism mediating the effects of nicotine on human behavior.
COMPREHENSIVE PSYCHIATRY
(2023)
Article
Chemistry, Organic
Shinya Tabata, Mai Minoshima, Akihiro Kobayashi, Takamitsu Hosoya, Suguru Yoshida
Summary: Migrative thioamination of aryne intermediates using o-iodoaryl triflates and sulfilimines leads to the formation of highly functionalized o-thioaminated diaryl sulfides. The ring expansion of cyclic sulfilimines enables the synthesis of eight- and nine-membered organosulfur compounds from dibenzothiophene- and thianthrene-type sulfilimines, respectively.
Article
Chemistry, Organic
Jumpei Taguchi, Takumi Okuyama, Satomi Tomita, Takashi Niwa, Takamitsu Hosoya
Summary: An efficient method for producing 3-triazenylarynes from ortho-iodoaryl triflate-type precursors has been developed. The resulting arynes exhibit high regioselectivity in reactions with various arynophiles due to the presence of the triazenyl group. The 3-triazenylaryne precursors can be used as intermediates for the synthesis of diverse multisubstituted aromatic compounds through the transformation of the remaining triazenyl group in the aryne adducts and triazenyl group-directed ortho-C-H functionalization.
