Full Paper
Synthesis of Phaitanthrin E and Tryptanthrin through Amination/Cyclization Cascade
Takumi Abe,
Masaru Terasaki,
Takumi Abe
Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido, 061-0293, Japan
Search for more papers by this authorMasaru Terasaki
Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido, 061-0293, Japan
Search for more papers by this authorTakumi Abe,
Masaru Terasaki,
Takumi Abe
Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido, 061-0293, Japan
Search for more papers by this authorMasaru Terasaki
Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido, 061-0293, Japan
Search for more papers by this authorAbstract
Phaitanthrin E was biomimetically synthesized from methyl indole-3-carboxylate and methyl anthranilate or anthranilic acid using the ester group as an activating group. The reaction proceeds through NCS-mediated dearomatization/TFA-catalyzed protonation of indolenine/C(2) amination/Et3N-promoted aromatization and cyclization in one-pot procedure. This method is capable of converting simple biomass materials to phaitanthrin E. The synthesis not only allows assessment of antiproliferative activity, but also affords experimental support for the hypothetical biosynthetic pathway of phaitanthrin E. The resulting phaitanthrin E derivatives were evaluated for in vitro antiproliferative activity against human colorectal cancer cells (DLD-1). The biogenetic intermediate of phaitanthrin E showed higher antiproliferative activity than the natural product, phaitanthrin E. Furthermore, a concise synthesis of tryptanthrin is also accomplished from indole-3-carbaldehyde and methyl anthranilate using the aldehyde group as an activating group.
Supporting Information
Supporting information for this article is available on the WWW under https://doi.org/10.1002/hlca.201700284.
| Filename | Description |
|---|---|
| hlca201700284-sup-0001-SupInfo.pdfPDF document, 38 MB |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
References
- 1A. M. Tucker, P. Grundt, ‘The Chemistry of Tryptanthrin and Its Derivatives’, Arkivoc 2011, 2012 (i), 546 – 569.
- 2Y. Jahng, ‘Progress in the Studies on Tryptanthrin, an Alkaloid of History’, Arch. Pharmacal Res. 2013, 36, 517 – 535.
- 3U. A. Kshirsagar, ‘Recent Developments in the Chemistry of Quinazoline Alkaloids’, Org. Biomol. Chem. 2015, 13, 9336 – 9352.
- 4C.-W. Jao, W.-C. Lin, Y.-T. Wu, P.-L. Wu, ‘Isolation, Structure Elucidation, and Synthesis of Cytotoxic Tryptanthrin Analogues from Phaius mishmensis’, J. Nat. Prod. 2008, 71, 1275 – 1279.
- 5S. D. Vaidya, N. P. Argade, ‘A Biomimetic Synthesis of Phaitanthrin E Involving a Fragmentation of sp3 Carbon–Carbon Bond: Synthesis and Rearrangement of Phaitanthrin D to Phaitanthrin E’, Org. Lett. 2015, 17, 6218 – 6221.
- 6C.-F. Chang, Y.-L. Hsu, C.-Y. Lee, C.-H. Wu, Y.-C. Wu, T.-H. Chuang, ‘Isolation and Cytotoxity Evaluation of the Chemical Constituents from Cephalantheropsis gracilis’, Int. J. Mol. Sci. 2015, 16, 3980 – 3989.
- 7C.-W. Jao, T.-H. Hung, C.-F. Chang, T.-H. Chuang, ‘Chemical Constituents of Phaius mishmensis’, Molecules 2016, 21, 1605 – 1614.
- 8E. Fiedler, H.-P. Fiedler, A. Gerhard, W. Keller-Schierlein, W. A. König, H. Zähner, ‘Synthese und Biosynthese Substituierter Tryptanthrine’, Arch. Microbiol. 1976, 107, 249 – 256.
- 9S. D. Vaidya, N. P. Argade, ‘Synthesis of (–)-Phaitanthrin D and (+)-Dihydropyrroloindoloquinazolinone’, Synthesis 2016, 48, 2896 – 2903.
- 10S. D. Vaidya, N. P. Argade, ‘Rearrangement of Imine Double Bond in Activated Quinazolinones: Synthesis of Phaitanthrin E’, Indian J. Chem., Sect. B 2017, 56, 527 – 530.
- 11T. Abe, T. Itoh, T. Choshi, S. Hibino, M. Ishikura, ‘One-Pot Synthesis of Tryptanthrin by the Dakin Oxidation of Indole-3-carbaldehyde’, Tetrahedron Lett. 2014, 55, 5268 – 5270.
- 12T. Itoh, T. Abe, S. Nakamura, M. Ishikura, ‘Cu-Mediated Oxidative Dimerization of Skatole to Tryptanthrin, an Indolo[2,1-b]quinazolone Alkaloid’, Heterocycles 2015, 91, 1423 – 1428.
- 13T. Itoh, T. Abe, T. Choshi, T. Nishiyama, M. Ishikura, ‘Synthesis of (±)-Cephalanthrin A using Baeyer-Villiger Oxidation’, Heterocycles 2017, 95, 507 – 516.
- 14T. Itoh, T. Abe, T. Choshi, T. Nishiyama, M. Ishikura, ‘A One-Pot Synthesis of Phaitanthrin E Through Intermolecular Condensation/Intramolecular C–H Amination Cascade’, Heterocycles 2016, 92, 1132 – 1136.
- 15T. Abe, K. Yamada, ‘Amination/Cyclization Cascade by Acid-Catalyzed Activation of Indolenine for the One-Pot Synthesis of Phaitanthrin E’, Org. Lett. 2016, 18, 6504 – 6507.
- 16A. S. Kende, J. Fan, Z. Chen, ‘A Concise Total Synthesis of (±)-Alantrypinone by a Novel Hetero-Diels–Alder Reaction’, Org. Lett. 2003, 5, 3205 – 3208.
- 17J.-F. Liu, P. Ye, K. Sprague, D. Yohannes, C. M. Baldino, C. J. Wilson, S.-C. Ng, ‘Novel One-Pot Total Syntheses of Deoxyvasicinone, Mackinazolinone, Isaindigotone, and Their Derivatives Promoted by Microwave Irradiation’, Org. Lett. 2005, 7, 3363 – 3366.
- 18T. Abe, K. Kida, K. Yamada, ‘A Copper-Catalyzed Ritter-Type Cascade via Iminoketene for the Synthesis of Quinazolin-4(3H)-ones and Diazocines’, Chem. Commun. 2017, 53, 4362 – 4365.
- 19X. Li, H. Huang, C. Yu, Y. Zhang, H. Li, W. Wang, ‘Synthesis of Tryptanthrins by Organocatalytic and Substrate Co-catalyzed Photochemical Condensation of Indoles and Anthranilic Acids with Visible Light and O2’, Org. Lett. 2016, 18, 5744 – 5747.
- 20K. C. Nicolaou, D. J. Edmonds, P. G. Bulger, ‘Cascade Reactions in Total Synthesis’, Angew. Chem. Int. Ed. 2006, 45, 7134 – 7186.
- 21M. Bandini, ‘Electrophilicity: The “Dark-Side” of Indole Chemistry’, Org. Biomol. Chem. 2013, 11, 5206 – 5212.
- 22C. C. J. Loh, D. Enders, ‘Exploiting the Electrophilic Properties of Indole Intermediates: New Options in Designing Asymmetric Reactions’, Angew. Chem. Int. Ed. 2012, 51, 46 – 48.
- 23M. Makosza, K. Wojciechowski, ‘Nucleophilic Substitution of Hydrogen in Heterocyclic Chemistry’, Chem. Rev. 2004, 104, 2631 – 2666.
- 24N. Morimoto, K. Morioku, H. Suzuki, Y. Takeuchi, Y. Nishina, ‘Lewis Acid and Fluoroalcohol Mediated Nucleophilic Addition to the C2 Position of Indoles’, Org. Lett. 2016, 18, 2020 – 2023.
- 25J. A. González-Vera, M. T. García-López, R. Herranz, ‘Unprecedented Stereospecific Synthesis of a Novel Tetracyclic Ring System, a Hybrid of Tetrahydropyrrolo[2,3-b]indole and Tetrahydroimidazo[1,2-a]indole, via a Domino Reaction upon a Tryptophan-Derived Amino Nitrile’, Org. Lett. 2004, 6, 2641 – 2644.
- 26B. Tréguier, S. P. Roche, ‘Double Annulative Cascade of Tryptophan-Containing Peptides Triggered by Selectfluor’, Org. Lett. 2014, 16, 278 – 281.
- 27T. Chen, T. J. Y. Foo, Y.-Y. Yeung, ‘Indole-Catalyzed Bromolactonization in Lipophilic Solvent: A Solid–Liquid Phase Transfer Approach’, ACS Catal. 2015, 5, 4751 – 4755.
- 28D. V. C. Awang, A. Vincent, D. Kindack, ‘The Chloroindolenine – Imino Ether – Oxindole Sequence. A Reexamination’, Can. J. Chem. 1984, 62, 2667 – 2675.
- 29K. I. Booker-Milburn, M. Fedouloff, S. J. Paknoham, J. B. Strachan, J. L. Melville, M. Voyle, ‘A New Claisen Sequence for the Synthesis of 3-Substituted-2-Oxindoles’, Tetrahedron Lett. 2000, 41, 4657 – 4661.
- 30J. Bergman, R. Engqvist, C. Stålhandske, H. Wallberg, ‘Studies on the Reactions Between Indole-2,3-diones (Isatins) and 2-Aminobenzylamine’, Tetrahedron 2003, 59, 1033 – 1048.
- 31R. Engqvist, J. Bergman, ‘Synthesis of Benzothiopyrano[2,3-b]indol-11-one and Benzopyrano[2,3-b]indol-11-one’, Tetrahedron 2003, 59, 9649 – 9653.
- 32L. He, L. Yang, S. L. Castle, ‘Synthesis of the Celogentin C Right-Hand Ring’, Org. Lett. 2006, 8, 1165 – 1168.
- 33W. Hu, F. Zhang, Z. Xu, Q. Liu, Y. Cui, Y. Jia, ‘Stereocontrolled and Efficient Total Synthesis of (−)-Stephanotic Acid Methyl Ester and (−)-Celogentin C’, Org. Lett. 2010, 12, 956 – 959.
- 34B. Ma, B. Banerjee, D. N. Litvinov, L. He, S. L. Castle, ‘Total Synthesis of the Antimitotic Bicyclic Peptide Celogentin C’, J. Am. Chem. Soc. 2010, 132, 1159 – 1171.
- 35Y. Feng, G. Chen, ‘Total Synthesis of Celogentin C by Stereoselective C–H Activation’, Angew. Chem. Int. Ed. 2010, 49, 958 – 961.
- 36Y.-X. Li, K.-G. Ji, H.-X. Wang, S. Ali, Y.-M. Liang, ‘Iodine-Induced Regioselective C–C and C–N Bonds Formation of N-Protected Indoles’, J. Org. Chem. 2011, 76, 744 – 747.
- 37W.-B. Wu, J.-M. Huang, ‘Highly Regioselective C–N Bond Formation through C–H Azolation of Indoles Promoted by Iodine in Aqueous Media’, Org. Lett. 2012, 14, 5832 – 5835.
- 38K. G. Liu, A. J. Robichaud, J. R. Lo, J. F. Mattes, Y. Cai, ‘Rearrangement of 3,3-Disubstituted Indolenines and Synthesis of 2,3-Substituted Indoles’, Org. Lett. 2006, 8, 5769 – 5771.
- 39J. F. Austin, S.-G. Kim, C. J. Sinz, W.-J. Xiao, D. W. C. MacMillan, ‘Enantioselective Organocatalytic Construction of Pyrroloindolines by a Cascade Addition-Cyclization Strategy: Synthesis of (–)-flustramine B’, Proc. Natl. Acad. Sci. U.S.A. 2004, 101, 5482 – 5487.
- 40M. Poirier, S. Goudreau, J. Poulin, J. Savoie, P. L. Beaulieu, ‘Metal-Free Coupling Azoles with 2- and 3-Haloindoles Providing Access to Novel 2- or 3-(Azol-1-yl)indole Derivatives’, Org. Lett. 2010, 12, 2334 – 2337.
- 41S. Y. Leong, P. W. Smith, B. Zou, ‘An Efficient Synthesis of Spiroquinoxalinones via Tandem Reactions’, Chin. J. Chem. 2014, 32, 1217 – 1220.
- 42R. C. Samanta, H. Yamamoto, ‘Selective Halogenation Using an Aniline Catalyst’, Chem. Eur. J. 2015, 21, 11976 – 11979.
- 43S. Lu, R. Wang, Y. Yang, Y. Li, Z. Shi, W. Zhang, Z. Tu, ‘Photoinduced Cyclization of 3-Acyl-2-halo-1-[(ω-phenylethynyl)alkyl]indoles to Azaheterocyclo[1,2,3-Im]-Fused Benzo[c]carbazoles’, J. Org. Chem. 2011, 76, 5661 – 5669.
- 44R. M. Wilson, W. S. Patterson, S. C. Austen, D. M. Ho, J. A. Krause Bauer, ‘Orbital Symmetry Governed Reactions under High-Intensity Argon Laser-Jet Conditions: The Involvement of a [1,5s] Sigmatropic Shift in the Photocyclization of an o-Alkenylbenzaldehyde to a Benzocyclobutenone’, J. Am. Chem. Soc. 1995, 117, 7820 – 7821.
- 45T. Morimoto, K. Fuji, K. Tsutsumi, K. Kakiuchi, ‘CO-Transfer Carbonylation Reactions. A Catalytic Pauson–Khand-Type Reaction of Enynes with Aldehydes as a Source of Carbon Monoxide’, J. Am. Chem. Soc. 2002, 124, 3806 – 3807.
- 46Q. Shuai, L. Yang, X. Guo, O. Baslé, C.-J. Li, ‘Rhodium-Catalyzed Oxidative C–H Arylation of 2-Arylpyridine Derivatives via Decarbonylation of Aromatic Aldehydes’, J. Am. Chem. Soc. 2010, 132, 12212 – 12213.
- 47J. Tsuji, K. Ohno, ‘Organic Syntheses by Means of Nobel Metal Compounds XXI. Decarbonylation of Aldehydes Using Rhodium Complex’, Tetrahedron Lett. 1965, 6, 3969 – 3971.
- 48X. Liu, X. Li, H. Liu, Q. Guo, J. Lan, R. Wang, J. You, ‘Aldehyde as a Traceless Directing Group for Rh(III)-Catalyzed C–H Activation: A Facile Access to Diverse Indolo[1,2-a]quinolines’, Org. Lett. 2015, 17, 2936 – 2939.
- 49J. Bergman, U. Tilstam, K.-W. Törnroos, ‘Reduction and Stereochemical Studies Through n.m.r. and X-ray Techniques of Indolo[2,1-b]quinazolines’, J. Chem. Soc., Perkin Trans. 1987, 1, 519 – 527.
- 50A. M. Francoeur, A. Assalian, ‘Microcat: A Novel Cell Proliferation and Cytotoxity Assay Based on WST-1’, Biochemica 1996, 3, 19 – 25.
