Synthesis of Potential Anticancer 1-(1H-Indol-3-yl)isoquinolines by Silver Nitrate Mediated Tandem Reactions of 2-Alkynyl­benzaldehyde Azines and Indoles

Yun-Hui Zhao; Yueyang Luo; Yingli Zhu; Hang Wang; Hangbin Zhou; Hailong Tan; Zhihua Zhou; Yong-Cheng Ma; Wenlin Xie; Zilong Tang

doi:10.1055/s-0036-1591743

Synlett, Table of Contents

Synlett 2018; 29(06): 773-778
DOI: 10.1055/s-0036-1591743

letter

Synthesis of Potential Anticancer 1-(1H-Indol-3-yl)isoquinolines by Silver Nitrate Mediated Tandem Reactions of 2-Alkynylbenzaldehyde Azines and Indoles

Yun-Hui Zhao*

^aSchool of Chemistry and Chemical Engineering, Hunan University of Science and Technology, Xiangtan, Hunan, 411201, P. R. of China

^dHunan Provincial Key Laboratory of Controllable Preparation and Functional Application of Fine Polymers, Hunan University of Science and Technology, Xiangtan 411201, P. R. of China Email: zhao_yunhui@163.com

,

Yueyang Luo

^aSchool of Chemistry and Chemical Engineering, Hunan University of Science and Technology, Xiangtan, Hunan, 411201, P. R. of China

,

Yingli Zhu

^bClinical Pharmacology Laboratory, Zhengzhou University People’s Hospital, No. 7, Wei Wu Road, Zhengzhou, Henan, 450003, P. R. of China

,

Hang Wang

^aSchool of Chemistry and Chemical Engineering, Hunan University of Science and Technology, Xiangtan, Hunan, 411201, P. R. of China

,

Hangbin Zhou

^aSchool of Chemistry and Chemical Engineering, Hunan University of Science and Technology, Xiangtan, Hunan, 411201, P. R. of China

,

Hailong Tan

^aSchool of Chemistry and Chemical Engineering, Hunan University of Science and Technology, Xiangtan, Hunan, 411201, P. R. of China

,

Zhihua Zhou*

^aSchool of Chemistry and Chemical Engineering, Hunan University of Science and Technology, Xiangtan, Hunan, 411201, P. R. of China

^dHunan Provincial Key Laboratory of Controllable Preparation and Functional Application of Fine Polymers, Hunan University of Science and Technology, Xiangtan 411201, P. R. of China Email: zhao_yunhui@163.com

,

Yong-Cheng Ma*

^bClinical Pharmacology Laboratory, Zhengzhou University People’s Hospital, No. 7, Wei Wu Road, Zhengzhou, Henan, 450003, P. R. of China

,

Wenlin Xie

^aSchool of Chemistry and Chemical Engineering, Hunan University of Science and Technology, Xiangtan, Hunan, 411201, P. R. of China

^dHunan Provincial Key Laboratory of Controllable Preparation and Functional Application of Fine Polymers, Hunan University of Science and Technology, Xiangtan 411201, P. R. of China Email: zhao_yunhui@163.com

,

Zilong Tang

^cKey Laboratory of Theoretical Chemistry and Molecular Simulation, Ministry of Education, P. R. of China

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Abstract

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Abstract

Novel antitumor compounds featuring isoquinoline and indole moieties were synthesized by a silver nitrate promoted domino reaction involving intramolecular cyclization, nucleophilic addition of indole, and subsequent N–N bond cleavage. The transformation from readily available starting materials into an interesting class of indole-substituted isoquinolines was completed under mild conditions and by simple operations in moderate to good yields. The antitumor activity of these compounds in vitro was significantly greater than that of a reference compound, 5-fluorouracil. The products might serve as new lead compounds for drugs for the treatment of cancer.

Key words

bond cleavage - domino reaction - isoquinolines - indoles - silver nitrate - medicinal chemistry

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References

References and Notes
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21 1-(1H-Indol-3-yl)-3-phenylisoquinoline (3a); Typical Procedure AgNO₃ (50.7 mg, 0.3 mmol) and indole (2; 35.1 mg, 0.3 mmol) were added to a solution of 1,2-bis[2-(phenylethynyl)benzylidene]hydrazine (1a; 91.8 mg, 0.225 mmol) in DMSO (1.5 mL). The mixture was stirred at 80 °C until consumption of 1a was complete (TLC). The solid was removed by filtration, and the filtrate was diluted with H₂O (5 mL) and extracted with EtOAc (3 × 15 mL). The organic phases were combined, dried (Na₂SO₄), and concentrated under reduced pressure. The residue was subjected to column chromatography [silica gel, EtOAc–hexanes (1:5)] to give a light-brown solid; yield: 74.9 mg (78%); mp 234–236 °C. IR (KBr): 3162, 1619, 1551, 1492, 1400, 1242, 1135 cm^–1. ¹H NMR (500 MHz, DMSO-d₆ ,): δ = 11.74 (s, 1 H), 8.46 (d, J = 8.5 Hz, 1 H), 8.33–8.31 (m, 3 H), 8.09–8.01 (m, 3 H), 7.79 (t, J = 7.5 Hz, 1 H), 7.65 (t, J = 7.5 Hz, 1 H), 7.58–7.54 (m, 3 H), 7.45 (t, J = 7.5 Hz, 1 H), 7.24 (t, J = 7.5 Hz, 1 H), 7.17 (t, J = 7.5 Hz, 1 H). ¹³C NMR (125 MHz, DMSO-d₆ ): δ = 155.1, 148.8, 139.1, 137.7, 136.5, 130.2, 128.8, 128.5, 127.9, 127.7, 127.3, 127.1, 126.8, 126.5, 125.4, 121.9, 120.6, 120.0, 113.6, 111.8. HRMS (ESI): m/z [M + H]⁺ calcd for C₂₃H₁₇N₂: 321.1392; found: 321.1396.

Supplementary Material

Supporting Information

Synthesis of Potential Anticancer 1-(1H-Indol-3-yl)isoquinolines by Silver Nitrate Mediated Tandem Reactions of 2-Alkynyl­benzaldehyde Azines and Indoles

Synthesis of Potential Anticancer 1-(1H-Indol-3-yl)isoquinolines by Silver Nitrate Mediated Tandem Reactions of 2-Alkynylbenzaldehyde Azines and Indoles