Synthesis of Carboranes Containing an Azulene Framework and in Vitro Evaluation as Boron CarriersClick to copy article linkArticle link copied!
Abstract
3-(o-Carboranylhydroxymethyl)-7-isopropylazulene sodium carboxylate (1) and 3-(o-carboranylmethyl)-7-isopropylazulene sodium sulfonate (2) were synthesized from the palladium-catalyzed addition reaction of 1-carboranyltributylstannnane (4) to azulene aldehydes (3 and 9). Although the water solubility of 1 was of the order of 10-6 M, that of 2 was of the order of 10-3 M and was enough for clinical use. The cytotoxicity of 1 (IC50) toward B-16 melanoma cells was of the order of 10-5 M, whereas that of 2 was of the order of 10-4 M. This value was close to that of BPA (∼9 × 10-3 M) which is utilized for clinical use. The boron uptake by B-16 cells was 0.17 μg of B/106 cells for 1 and 0.25 μg of B/106 cells for 2. It is clear that compound 2 accumulates in B-16 melanoma cells with a significantly high level although it is highly water soluble and its cytotoxicity is significantly low.
*
In papers with more than one author, the asterisk indicates the name of the author to whom inquiries about the paper should be addressed.
✗
Abstract published in Advance ACS Abstracts, August 1, 1997.
Cited By
Smart citations by scite.ai include citation statements extracted from the full text of the citing article. The number of the statements may be higher than the number of citations provided by ACS Publications if one paper cites another multiple times or lower if scite has not yet processed some of the citing articles.
This article is cited by 36 publications.
- Daniel Eppel, Nils Oberhof, Martin C. Dietl, Patrick Cieslik, Matthias Rudolph, Lukas Eberle, Petra Krämer, Fabian Stuck, Frank Rominger, Andreas Dreuw, A. Stephen K. Hashmi. Gold(III) Meets Azulene: A Class of [(tBuC∧N∧C)AuIII(azulenyl)] Pincer Complexes. Organometallics 2021, 40
(23)
, 3865-3870. https://doi.org/10.1021/acs.organomet.1c00535
- Tamiris B. Grimaldi, Davi F. Back, and Gilson Zeni . Potassium tert-Butoxide Promoted Annulation of 2-Alkynylphenyl Propargyl Ethers: Selective Synthesis of Benzofuran and 12H-Benzoannulene Derivatives. The Journal of Organic Chemistry 2013, 78
(21)
, 11017-11031. https://doi.org/10.1021/jo4020062
- Matthias Scholz and Evamarie Hey-Hawkins . Carbaboranes as Pharmacophores: Properties, Synthesis, and Application Strategies. Chemical Reviews 2011, 111
(11)
, 7035-7062. https://doi.org/10.1021/cr200038x
- Toshihisa Shibasaki, Takeo Ooishi, Nobuhiko Yamanouchi, Toshihiro Murafuji, Kei Kurotobi and Yoshikazu Sugihara . A New Efficient Route to 2-Substituted Azulenes Based on Sulfonyl Group Directed Lithiation. The Journal of Organic Chemistry 2008, 73
(20)
, 7971-7977. https://doi.org/10.1021/jo801166f
- Hiroyuki Nakamura,, Takaya Kamakura, and, Shinya Onagi. 1,2-Bis(diphenylphosphino)carborane As a Dual Mode Ligand for Both the Sonogashira Coupling and Hydride-Transfer Steps in Palladium-Catalyzed One-Pot Synthesis of Allenes from Aryl Iodides. Organic Letters 2006, 8
(10)
, 2095-2098. https://doi.org/10.1021/ol060538v
- Igor B. Sivaev,, Alexandr B. Bruskin,, Vladimir V. Nesterov,, Mikhail Yu. Antipin,, Vladimir I. Bregadze, and, Stefan Sjöberg. Synthesis of Schiff Bases Derived from the Ammoniaundecahydro-closo-dodecaborate(1−) Anion, [B12H11NHCHR]-, and Their Reduction into Monosubstituted Amines [B12H11NH2CH2R]-: A New Route to Water Soluble Agents for BNCT. Inorganic Chemistry 1999, 38
(25)
, 5887-5893. https://doi.org/10.1021/ic990013h
- Albert H. Soloway,, Werner Tjarks,, Beverly A. Barnum,, Feng-Guang Rong,, Rolf F. Barth,, Iwona M. Codogni, and, J. Gerald Wilson. The Chemistry of Neutron Capture Therapy. Chemical Reviews 1998, 98
(4)
, 1515-1562. https://doi.org/10.1021/cr941195u
- Hiroyuki Nakamura,, Kouichi Aoyagi, and, Yoshinori Yamamoto. Tetrabutylammonium Fluoride Promoted Novel Reactions of o-Carborane: Inter- and Intramolecular Additions to Aldehydes and Ketones and Annulation via Enals and Enones. Journal of the American Chemical Society 1998, 120
(6)
, 1167-1171. https://doi.org/10.1021/ja973832e
- Finn Schulz, Bettina Lutz, Daniel Rück, Derman Batman, Wolfgang Frey, Sabine Laschat. Tailoring liquid crystalline self-assembly and de Vries behavior of azulenes
via
lateral and core substitution. Soft Matter 2023, 19
(13)
, 2397-2406. https://doi.org/10.1039/D3SM00205E
- Taku Shoji, Naoko Sakata, Ryuta Sekiguchi, Shunji Ito. Bis(3-methylthio-1-azulenyl)phenylmethyl Cations and Dications Connected by a 1,4-Phenylene Spacer: Synthesis and Their Electrochemical Properties. Organics 2022, 3
(4)
, 507-519. https://doi.org/10.3390/org3040034
- Roberto do Carmo Pinheiro, Luiz Eduardo Welter, Bernardo A. Iglesias, Davi F. Back, Luiza Souza Marques, Cristina Wayne Nogueira, Gilson Zeni. Base‐Catalyzed Sequential 5‐
exo
‐dig/7‐
endo
‐dig Cyclization of (2‐Alkynylphenyl) Benzyl Ethers: Scope, Mechanism Studies, and Photophysical Properties. European Journal of Organic Chemistry 2022, 2022
(39)
https://doi.org/10.1002/ejoc.202200984
- Taku Shoji, Shunji Ito, Masafumi Yasunami. Synthesis of Azulene Derivatives from 2H-Cyclohepta[b]furan-2-ones as Starting Materials: Their Reactivity and Properties. International Journal of Molecular Sciences 2021, 22
(19)
, 10686. https://doi.org/10.3390/ijms221910686
- Ahmed H. M. Elwahy, Klaus Hafner. Alkynylazulenes as Building Blocks for Highly Unsaturated Scaffolds. Asian Journal of Organic Chemistry 2021, 10
(8)
, 2010-2083. https://doi.org/10.1002/ajoc.202100301
- Finn Schulz, Philipp Ehni, Bianca Wank, Alina Bauer, Wolfgang Frey, Sabine Laschat. Alkoxy-bromo-azulenes displaying ambient temperature smectic E-phases. Liquid Crystals 2021, 48
(6)
, 832-843. https://doi.org/10.1080/02678292.2020.1821919
- Vanessa Claus, Michael Schukin, Siegfried Harrer, Matthias Rudolph, Frank Rominger, Abdullah M. Asiri, Jin Xie, A. Stephen K. Hashmi. Direkter Zugang zu Azulenen über eine Gold‐katalysierte Dimerisierung von Diarylalkinen. Angewandte Chemie 2018, 130
(39)
, 13148-13152. https://doi.org/10.1002/ange.201805918
- Vanessa Claus, Michael Schukin, Siegfried Harrer, Matthias Rudolph, Frank Rominger, Abdullah M. Asiri, Jin Xie, A. Stephen K. Hashmi. Gold‐Catalyzed Dimerization of Diarylalkynes: Direct Access to Azulenes. Angewandte Chemie International Edition 2018, 57
(39)
, 12966-12970. https://doi.org/10.1002/anie.201805918
- Taku Shoji, Shunji Ito. Azulene‐Based Donor–Acceptor Systems: Synthesis, Optical, and Electrochemical Properties. Chemistry – A European Journal 2017, 23
(66)
, 16696-16709. https://doi.org/10.1002/chem.201702806
- Taku Shoji, Daichi Nagai, Miwa Tanaka, Takanori Araki, Akira Ohta, Ryuta Sekiguchi, Shunji Ito, Shigeki Mori, Tetsuo Okujima. Synthesis of 2‐Aminofurans by Sequential [2+2] Cycloaddition–Nucleophilic Addition of 2‐Propyn‐1‐ols with Tetracyanoethylene and Amine‐Induced Transformation into 6‐Aminopentafulvenes. Chemistry – A European Journal 2017, 23
(21)
, 5126-5136. https://doi.org/10.1002/chem.201700121
- Muddamarri Hanumantha Rao, Krishnamurthi Muralidharan. closo-Dodecaborate (B12H12)2− salts with nitrogen based cations and their energetic properties. Polyhedron 2016, 115 , 105-110. https://doi.org/10.1016/j.poly.2016.03.062
- Rafaela Gai, Roberto do Carmo Pinheiro, José S. S. Neto, Bernardo A. Iglesias, Thiago V. Acunha, Davi F. Back, Gilson Zeni. The intramolecular 5-exo, 7-endo-dig transition metal-free cyclization sequence of (2-alkynylphenyl) benzyl ethers: synthesis of seven-membered fused benzo[b]furans. Green Chemistry 2016, 18
(24)
, 6648-6658. https://doi.org/10.1039/C6GC02423H
- Taku Shoji, Miwa Tanaka, Takanori Araki, Sho Takagaki, Ryuta Sekiguchi, Shunji Ito. Synthesis of 1-azulenyl ketones by Brønsted acid mediated hydration of 1-azulenylalkynes. RSC Advances 2016, 6
(82)
, 78303-78306. https://doi.org/10.1039/C6RA20010A
- Naoko Takenaga, Koichi Sato, Koh Fukazawa, Miki Maruko. Facile Synthesis of Guaiazulene-Heterocycle Hybrids via Ugi Multicomponent Reactions. HETEROCYCLES 2015, 90
(1)
, 113. https://doi.org/10.3987/COM-14-S(K)27
- Soumen Sarkar, Krishnendu Bera, Umasish Jana. Tandem C-3/C-2 annulation of indole, benzofuran, and benzothiophene with 2-alkynyl benzylalcohol: an efficient approach to the diverse tetracyclic heteroazulene ring systems. Tetrahedron Letters 2014, 55
(45)
, 6188-6192. https://doi.org/10.1016/j.tetlet.2014.09.050
- Koichi Sato, Takumi Ozu, Naoko Takenaga. Solvent-free synthesis of azulene derivatives via Passerini reaction by grinding. Tetrahedron Letters 2013, 54
(7)
, 661-664. https://doi.org/10.1016/j.tetlet.2012.11.148
- Koichi Sato, Erina Yokoo, Naoko Takenaga. FACILE SYNTHESIS OF GUAIAZULENE-HETEROCYCLE HYBRIDS VIA MULTICOMPONENT REACTIONS INVOLVING FORMATION OF ZWITTERIONIC INTERMEDIATES. HETEROCYCLES 2013, 87
(4)
, 807. https://doi.org/10.3987/COM-13-12680
- Chi-Phi Wu, Badugu Devendar, Hui-Chi Su, Ya-Hui Chang, Chien-Kuo Ku. Efficient synthesis and applications of 2-substituted azulene derivatives: towards highly functionalized carbo- and heterocyclic molecules. Tetrahedron Letters 2012, 53
(37)
, 5019-5022. https://doi.org/10.1016/j.tetlet.2012.07.040
- Hiroyuki Nakamura. Liposomal Boron Delivery for Neutron Capture Therapy. 2009, 179-208. https://doi.org/10.1016/S0076-6879(09)65010-2
- Hiroyuki Nakamura, Jong-Dae Lee, Manabu Ueno, Yusuke Miyajima, Hyun Seung Ban. Synthesis of closo-Dodecaboryl Lipids and their Liposomal Formation for Boron Neutron Capture Therapy. NanoBiotechnology 2007, 3
(2)
, 135-145. https://doi.org/10.1007/s12030-008-9000-6
- Alexandra L. Pickering, Christoph Mitterbauer, Nigel D. Browning, Susan M. Kauzlarich, Philip P. Power. Room temperature synthesis of surface-functionalised boron nanoparticles. Chemical Communications 2007, 410
(6)
, 580. https://doi.org/10.1039/b614363f
- Toru Asano, Hiroyuki Nakamura, Yoshimasa Uehara, Yoshinori Yamamoto. Design, Synthesis, and Biological Evaluation of Aminoboronic Acids as Growth‐Factor Receptor Inhibitors of EGFR and VEGFR‐1 Tyrosine Kinases. ChemBioChem 2004, 5
(4)
, 483-490. https://doi.org/10.1002/cbic.200300748
- Hiroyuki Nakamura, Yusuke Miyajima, Toshiaki Takei, Satoshi Kasaoka, Kazuo Maruyama. Synthesis and vesicle formation of a nido-carborane cluster lipid for boron neutron capture therapy. Chem. Commun. 2004, 32
(17)
, 1910-1911. https://doi.org/10.1039/B406141A
- John F Valliant, Katharina J Guenther, Arienne S King, Pierre Morel, Paul Schaffer, Oyebola O Sogbein, Karin A Stephenson. The medicinal chemistry of carboranes. Coordination Chemistry Reviews 2002, 232
(1-2)
, 173-230. https://doi.org/10.1016/S0010-8545(02)00087-5
- Hiroyuki Nakamura, Masaru Fujiwara, Yoshinori Yamamoto. A Practical Method for the Synthesis of Enantiomerically Pure 4-Borono-L-phenylalanine. Bulletin of the Chemical Society of Japan 2000, 73
(1)
, 231-235. https://doi.org/10.1246/bcsj.73.231
- Giovanni Battista Giovenzana, Luigi Lay, Diego Monti, Giovanni Palmisano, Luigi Panza. Synthesis of carboranyl derivatives of alkynyl glycosides as potential BNCT agents. Tetrahedron 1999, 55
(49)
, 14123-14136. https://doi.org/10.1016/S0040-4020(99)00878-9
- Hiroyuki Nakamura, Kouichi Aoyagi, Yoshinori Yamamoto. Synthetic utility of o-carborane: novel protective group for aldehydes and ketones. Journal of Organometallic Chemistry 1999, 574
(1)
, 107-115. https://doi.org/10.1016/S0022-328X(98)00922-X
- Axel Herzog, Carolyn B. Knobler, M. Frederick Hawthorne. Die Anwendung der Barton-Reaktion in der Carboranchemie – Synthese von 2-Hydroxyimino-1-hydroxymethylnona-B-methyl-1,12- dicarba-closo-dodecaboran(12). Angewandte Chemie 1998, 110
(11)
, 1661-1665. https://doi.org/10.1002/(SICI)1521-3757(19980605)110:11<1661::AID-ANGE1661>3.0.CO;2-4
Article Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.
Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.
The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated.