CC BY ND NC 4.0 · SynOpen 2017; 01(01): 0008-0010
DOI: 10.1055/s-0036-1588167
letter
Copyright with the author

Ultrasound-Accelerated Amide Coupling Reactions Directed toward the Synthesis of 1-Acetyl-3-carboxamide-β-carboline Derivatives of Biological Importance

N. Sharmaa, P. Kumaria, P. Sharmaa, N. Bhagatb, S. Bhagat*a
  • aOrganic Synthesis research Laboratory, Department of Chemistry, A.R.S.D. College, University of Delhi, New Delhi-110021, India
  • bInstrumentation & Control Engineering, Netaji Subash Institute of Technology, University of Delhi, Azad Hind Fauz Marg, Dwarka, Delhi-110078, India   Email: sunitabhagat28@gmail.com
Further Information

Publication History

Received: 03 February 2017

Accepted after revision: 12 March 2017

Publication Date:
22 March 2017 (online)

 

Abstract

Several biologically important 1-acetyl-3-carboxamide-β-carboline derivatives were rapidly synthesized by ultrasound-promoted amide coupling of 1-acetyl-9H-pyrido[3,4-b]indole-3-carboxylic acid with substituted aromatic amines. The major advantages of the proposed method are that use of ultrasound irradiations afforded the desired products in a drastically reduced reaction time and in excellent yields compared with conventional stirring.


#

Marine natural products have increasingly become major leads in drug discovery, often showing a unique biochemical mode of action.[1] [2] Indoles continue to attract extensive synthetic interest, due to their divergent pharmacological activities and also because the rigid framework can lead to compounds of marked selectivity in their interactions with enzymes or receptors.[3–8]

The β-carboline ring system containing a pyridoindole structure is a component of structures with a vast spectrum of biological properties,[9] [10] [11] [12] [13] [14] [15] [16] such as antimicrobial,[17] antiviral,[18] antitumor,[19] [20] anticonvulsant,[21] and parasiticidal activity.[22] Other β-carboline derivatives inhibit cyclin-dependent kinase (CDK) 1, IkappaB kinase (IKK), and topoisomerase I.[23] However, an important challenge is the scarce natural availability of marine β-carbolines, which hinders biological screening in structure-activity relationship (SAR) studies. Therefore, efficient chemical synthesis[24] of these marine compounds in larger quantities is necessary to investigate their biological activities and is the focus of the work reported herein.

1-Acetyl-3-carboxamide-β-carboline derivatives have been synthesized by a biocatalytic pathway using the McbA enzyme.[25] However, yields of the target compounds are not high. Additionally, such biocatalytic approaches take longer to establish on an industrial scale.[26] Other synthetic approaches suffer from drawbacks such as multistep protocols,[27] or extended reaction times[28] with overall yields of 19% and 72%, respectively. Thus, there remains a need for the development of more efficient, convenient and operationally simple approaches for the rapid synthesis of 1-acetyl-3-carboxamide-β-carboline derivatives.

Ultrasound-assisted organic reactions have emerged as an innovative technique in a wide variety of conversions.[27] [28] [29] [30] Use of ultrasound irradiation results in accelerated reaction rates, energy conservation and minimization of waste as compared with traditional methods.[31] In continuation of our interest in the synthesis of a wide range of heterocyclic systems,[32] we herein report a novel ultrasound-promoted amide coupling for the rapid synthesis of 1-acetyl-3-carboxamide-β-carboline derivatives in good to excellent yields with a notable reduction in completion time compared with classical methods of amide coupling.[33]

Firstly, synthesis of β-carboline derivatives 3ac, which are already known for their antimalarial activity,[34] was carried out by reacting 1-acetyl-9H-pyrido[3,4-b]indole-3-carboxylic acid (1)[35] with the phenylethanamines 2a/2b and indolyl ethanamine 2c under ultrasonic irradiation (UI) at room temperature (Table [1]). As outlined in Table [1], ultrasound irradiation reduced the completion time of the reactions from several hours to minutes and yields were also improved from 81–83% (under conventional conditions) to 91–92%. The NMR spectroscopic and mass spectrometric data were in excellent agreement with those reported previously.[34]

Table 1 Synthesis of 1-Acetyl-3-carboxamide-β-carboline Derivatives under Ultrasound Irradiation or Conventional Stirringa

Product

Ar

Ultrasonic irradiation

Conventional

Time (min)

Yield (%)b

Time (h)

Yield (%)b

3a

30

19

16

81

3b

30

92

18

83

3c

35

92

15

82

a Reaction conditions: 1 (1.0 equiv.), 2ac (1.2 equiv), DIPEA (2.1 equiv), EDC·HCl (1.1 equiv), HOBt (1.1 equiv), DMF, rt.

b Isolated yield.

We extended our study to demonstrate the substrate scope of the reaction with 1-acetyl-9H-pyrido[3,4-b]indole-3-carboxylic acid (1) using fluorinated and non-fluorinated aromatic amines 2dk for the formation of various 1-acetyl-3-carboxamide-β-carboline derivatives 3dk in excellent yields of 90–94% under ultrasonic irradiation (Table [2]). All products were analyzed by IR, 1H NMR, 13C NMR and HRMS analysis. From Table [2], it is clear that the reaction accommodated a range of substituents such as fluoro- and trifluoromethyl-groups at different positions on the aromatic ring.

Table 2 Substrate Scope of the Synthesis of Novel Fluorinated/Non­fluorinated β-Carboline Derivativesa

a Reaction conditions: 1 (1.0 equiv), 2dk (1.2 equiv), DIPEA (2.1 equiv), EDC­·HCl (1.1 equiv), HOBt (1.1 equiv), DMF, rt.

b Isolated yield.

In conclusion, we have reported an ultrasound-accelerated, efficient amide coupling reaction to provide efficient access to 1-acetyl-3-carboxamide-β-carboline derivatives. The products were obtained in excellent yields with short reaction times and the protocol accommodates a variety of functionality.


#

Acknowledgment

The authors are grateful to the SERB, Department of Science & Technology, for providing financial support and the USIC, University of Delhi for providing instrumentation facilities. NS is grateful to the DST-SERB for a Reseach Associate award and PK to the CSIR for a Senior Research Fellowship.

Supporting Information

  • References and Notes

    • 1a Copp BR. Keyzers RA. Munro MH. G. Princep MR. Nat. Prod. Rep. 2014; 31: 16
    • 1b Xiong ZQ. Wang JF. Hao YY. Wang Y. Mar. Drugs 2013; 11: 700
    • 2a Cragg GM. Newman DJ. Biochim. Biophys. Acta 2013; 1830: 3670
    • 2b Lam KS. Curr. Opin. Microbiol. 2006; 9: 245
  • 3 Bailey PD. Cochrane PJ. Forster AH. Morgana KM. Pearson DP. J. Tetrahedron Lett. 1999; 40: 4597
    • 4a Zheng C. Fang Y. Tong W. Li G. Zhou HW. Lin Q. Yang F. Yang Z. Wang P. Peng Y. Pang X. Yi Z. Luo J. Liu M. Chen Y. J. Med. Chem. 2014; 57: 600
    • 4b Winkler JD. Londregan AT. Hamann MT. Org. Lett. 2006; 8: 2591
  • 5 Tang JG. Wang YH. Wang RR. Dong ZJ. Yang LM. Zheng YT. Liu JK. Chemistry & Biodiversity 2008; 5: 447
  • 6 Kawasaki T. Higuchi K. Nat. Prod. Rep. 2005; 22: 761
    • 7a Herraiz T. Galisteo J. J. Agric. Food Chem. 2003; 51: 7156
    • 7b Chen H. Gao P. Zhang M. Liao W. Zhang J. New J. Chem. 2014; 38: 4155
  • 8 Ang KK. H. Holmes MJ. Higa T. Hamann MT. Kara UK. Antimicrob. Agents Chemother. 2000; 44: 1645
    • 9a Kusurkar RS. Goswami SK. Vyas SM. Tetrahedron Lett. 2003; 44: 4761
    • 9b Laine AE. Lood C. Koskinen AM. P. Molecules 2014; 19: 1544
  • 10 Airaksinen MM. Kari I. Med. Biol. 1981; 59: 21
  • 11 Carbrera GM. Seldes AM. J. Nat. Prod. 1999; 62: 759
  • 12 Lippke KP. Schunack WG. Wenning W. Mueller WE. J. Med. Chem. 1983; 26: 499
  • 13 Cain M. Weber RW. Guzman F. Cook JM. Barker SA. Rice KC. Crawley JN. Paul SM. Skolnick PJ. Med. Chem. 1982; 25: 1081
  • 14 Hagen TJ. Skolnick P. Cook JM. J. Med. Chem. 1987; 30: 750
  • 15 Dodd RH. Ouannes C. Carvalho LP. Valin A. Venault P. Chapouthier G. Rossier J. Potier P. J. Med. Chem. 1985; 28: 824
  • 16 Patel K. Gadewar M. Tripathi R. Prasad SK. Patel DK. Asian Pac. J. Trop. Biomed. 2012; 2: 660
  • 17 Cao R. Peng W. Wang Z. Zu A. Curr. Med. Chem. 2007; 14: 479
  • 18 Tang JG. Wang YH. Wang RR. Dong ZJ. Yang LM. Zheng YT. Liu JK. Chemistry & Biodiversity 2008; 5: 447
  • 19 Bemis DL. Capedice JL. Gorroochurn P. Katz AZ. Buttyan R. Int. J. Oncol. 2006; 29: 1065
  • 20 Cao R. Peng W. Chen H. Ma Y. Liu X. Hou X. Guan H. Xu A. Biochem. Biophys. Res. Commun. 2005; 338: 1557
  • 21 Dorey G. Dubois L. Potier P. Dodd RH. J. Med. Chem. 1995; 38: 189
  • 22 Winkler JD. Londregan AT. Hamann MT. Org. Lett. 2006; 8: 2591
  • 23 Castro AC. Dang LC. Soucy F. Grenier L. Mazdiyansi H. Hottelet M. Parent L. Pien C. Palombella VAdams J. Bioorg. Med. Chem. Lett. 2003; 13: 2419
  • 24 Nicolaou KC. Vourloumis D. Winssinger N. Baran PS. Angew. Chem. Int. Ed. 2000; 39: 44
  • 25 Ji C. Chen Q. Li Q. Huang H. Song Y. Maa J. Ju J. Tetrahedron Lett. 2014; 55: 4901
  • 26 Johannes T. Simurdiak MR. Zhao H. Encyclopedia of Chemical Processing . DOI: DOI: 10.1081/E-ECHP-120017565.
  • 27 Liu YQ. Li LH. Yang L. Li HY. Chem. Pap. 2010; 64: 533
  • 28 Meciarova M. Polackova V. Toma S. Chem. Pap. 2002; 56: 208
  • 29 Meciarova M. Toma S. Babiak P. Chem. Pap. 2004; 58: 104
  • 30 Tabatabaeian K. Mamaghani M. Mahmoodi NO. Khorshidi A. Catal. Commun. 2008; 9: 416
    • 31a Kumar V. Sharma A. Sharma M. Sharma UK. Sinha AK. Tetrahedron 2007; 63: 9718
    • 31b Sinha AK. Sharma A. Joshi BP. Tetrahedron 2007; 63: 960
    • 32a Sharma N. Chundawat TS. Bhagat S. Synthesis 2016; 48: 4495
    • 32b Chundawat TS. Sharma N. Kumari P. Bhagat S. Synlett 2016; 27: 404
    • 32c Chundawat TS. Sharma N. Kumari P. Bhagat S. Med. Chem. Res. 2016; 25: 2335
  • 33 Conventional method for the synthesis of 9H-pyrido[3,4-b]indole-3-carboxamide derivatives (3a–k); General procedure: To a stirred solution of 1 (1 equiv) in DMF were added EDC·HCl (1.1 equiv) and HOBt (1.1 equiv), followed by addition of DIPEA (2.1 equiv). The resulting reaction mixture was stirred at r.t. for 30 minutes. The requisite amine 2ac was added portionwise and the reaction was stirred at r.t. for 15–18 h (Table 1). Progress of reaction was monitored by TLC. After completion, the reaction mixture was poured into ice-cold water, and the precipitate filtered. Column chromatography on silica (100–200 mesh), eluting with 30–40% ethyl acetate/hexane gave the pure 1-acetyl-3-carboxamide-β-carboline derivatives 3ac.Ultrasound method for the synthesis of 1-acetyl-3-carboxamide-β-carboline derivatives (3a–k); General procedure: To a stirred solution of 1 (1equiv) in DMF were added EDC·HCl (1.1 equiv) and HOBt (1.1 equiv), followed by addition of DIPEA (2.1 equiv). The resulting reaction mixture was stirred at r.t. for 10 minutes. The requisite amine 2ak was added portionwise and the reaction was stirred at r.t. under sonication for the time detailed in Table 1 and Table 2. The progress of the reaction was monitored by TLC. After completion, the reaction mixture was poured into ice-cold water, and the precipitate filtered. Column chromatography on silica (100–200 mesh), eluting with 30–40% ethyl acetate/hexane gave the pure 1-acetyl-3-carboxamide-β-carboline derivatives 3ak.Representative Spectroscopic Data1-Acetyl-N-phenethyl-9H-pyrido[3,4-b]indole-3-carboxamide (3a): Pale-yellow solid; mp 172–174 °C; IR (KBr): 3349, 2914, 1683, 1534 cm–1; 1H NMR (400 MHz, CDCl3): δ = 10.31 (s, 1 H, -NH), 9.00 (s, 1 H), 8.12 (d, J = 7.63 Hz, 1 H), 8.00 (t, 1 H, -NH), 7.56–7.50 (m, 2 H), 7.31–7.18 (m, 6 H), 3.78 (q, J = 6.78 Hz, 2 H), 2.93 (t, J = 6.78 Hz, 2 H), 2.67 (s, 3 H); 13C NMR (100 MHz, CDCl3): δ = 202.2, 164.4, 141.4, 139.1, 139.0, 136.1, 133.4, 132.5, 129.6, 128.8, 128.7, 126.5, 122.2, 121.4, 120.9, 118.2, 112.1, 40.4, 35.8, 25.6; HRMS (ESI): m/z [M+H]+ calcd for C22H19N3O2: 358.1555; found: 358.1545.1-Acetyl-N-(2,4-difluorophenyl)-9H-pyrido[3,4-b]indole-3-carboxamide (3j): Yellow solid; mp 210–212 °C; IR (KBr): 3350, 2916, 1665, 1539 cm–1; 1H NMR (400 MHz, DMSO-d 6): δ = 12.29 (s, 1 H, -NH), 10.39 (s, 1 H, -NH), 9.19 (s, 1 H), 8.12 (q, J = 6.10 Hz, 1 H), 7.83 (d, J = 7.63 Hz, 1 H), 7.63 (t, J = 8.39 Hz, 1 H), 7.46–7.41 (m, 1 H), 7.34 (t, J = 7.63 Hz, 1 H), 7.17 (t, J = 8.39 Hz, 1 H), 2.93 (s, 3 H); 13C NMR (100 MHz, CDCl3): δ = 200.6, 162.5, 145.1, 142.9, 142.4, 137.2, 135.0, 133.9, 133.9, 132.2, 129.5, 122.4, 121.0, 120.2, 118.4, 113.4, 111.4, 104.5, 104.2, 25.9; HRMS (ESI): m/z [M+H]+ calcd for C20H13F2N3O2: 366.1054; found: 366.1061
  • 34 Huang H. Yao Y. He Z. Yang T. Ma J. Tian X. Li Y. Huang C. Chen X. Li W. Zhang S. Zhang C. Ju J. J. Nat. Prod. 2011; 74: 2122
  • 35 Tang J.-G. Liu H. Zhou Z.-Y. Liu J.-K. Synth. Commun. 2010; 40: 1411

  • References and Notes

    • 1a Copp BR. Keyzers RA. Munro MH. G. Princep MR. Nat. Prod. Rep. 2014; 31: 16
    • 1b Xiong ZQ. Wang JF. Hao YY. Wang Y. Mar. Drugs 2013; 11: 700
    • 2a Cragg GM. Newman DJ. Biochim. Biophys. Acta 2013; 1830: 3670
    • 2b Lam KS. Curr. Opin. Microbiol. 2006; 9: 245
  • 3 Bailey PD. Cochrane PJ. Forster AH. Morgana KM. Pearson DP. J. Tetrahedron Lett. 1999; 40: 4597
    • 4a Zheng C. Fang Y. Tong W. Li G. Zhou HW. Lin Q. Yang F. Yang Z. Wang P. Peng Y. Pang X. Yi Z. Luo J. Liu M. Chen Y. J. Med. Chem. 2014; 57: 600
    • 4b Winkler JD. Londregan AT. Hamann MT. Org. Lett. 2006; 8: 2591
  • 5 Tang JG. Wang YH. Wang RR. Dong ZJ. Yang LM. Zheng YT. Liu JK. Chemistry & Biodiversity 2008; 5: 447
  • 6 Kawasaki T. Higuchi K. Nat. Prod. Rep. 2005; 22: 761
    • 7a Herraiz T. Galisteo J. J. Agric. Food Chem. 2003; 51: 7156
    • 7b Chen H. Gao P. Zhang M. Liao W. Zhang J. New J. Chem. 2014; 38: 4155
  • 8 Ang KK. H. Holmes MJ. Higa T. Hamann MT. Kara UK. Antimicrob. Agents Chemother. 2000; 44: 1645
    • 9a Kusurkar RS. Goswami SK. Vyas SM. Tetrahedron Lett. 2003; 44: 4761
    • 9b Laine AE. Lood C. Koskinen AM. P. Molecules 2014; 19: 1544
  • 10 Airaksinen MM. Kari I. Med. Biol. 1981; 59: 21
  • 11 Carbrera GM. Seldes AM. J. Nat. Prod. 1999; 62: 759
  • 12 Lippke KP. Schunack WG. Wenning W. Mueller WE. J. Med. Chem. 1983; 26: 499
  • 13 Cain M. Weber RW. Guzman F. Cook JM. Barker SA. Rice KC. Crawley JN. Paul SM. Skolnick PJ. Med. Chem. 1982; 25: 1081
  • 14 Hagen TJ. Skolnick P. Cook JM. J. Med. Chem. 1987; 30: 750
  • 15 Dodd RH. Ouannes C. Carvalho LP. Valin A. Venault P. Chapouthier G. Rossier J. Potier P. J. Med. Chem. 1985; 28: 824
  • 16 Patel K. Gadewar M. Tripathi R. Prasad SK. Patel DK. Asian Pac. J. Trop. Biomed. 2012; 2: 660
  • 17 Cao R. Peng W. Wang Z. Zu A. Curr. Med. Chem. 2007; 14: 479
  • 18 Tang JG. Wang YH. Wang RR. Dong ZJ. Yang LM. Zheng YT. Liu JK. Chemistry & Biodiversity 2008; 5: 447
  • 19 Bemis DL. Capedice JL. Gorroochurn P. Katz AZ. Buttyan R. Int. J. Oncol. 2006; 29: 1065
  • 20 Cao R. Peng W. Chen H. Ma Y. Liu X. Hou X. Guan H. Xu A. Biochem. Biophys. Res. Commun. 2005; 338: 1557
  • 21 Dorey G. Dubois L. Potier P. Dodd RH. J. Med. Chem. 1995; 38: 189
  • 22 Winkler JD. Londregan AT. Hamann MT. Org. Lett. 2006; 8: 2591
  • 23 Castro AC. Dang LC. Soucy F. Grenier L. Mazdiyansi H. Hottelet M. Parent L. Pien C. Palombella VAdams J. Bioorg. Med. Chem. Lett. 2003; 13: 2419
  • 24 Nicolaou KC. Vourloumis D. Winssinger N. Baran PS. Angew. Chem. Int. Ed. 2000; 39: 44
  • 25 Ji C. Chen Q. Li Q. Huang H. Song Y. Maa J. Ju J. Tetrahedron Lett. 2014; 55: 4901
  • 26 Johannes T. Simurdiak MR. Zhao H. Encyclopedia of Chemical Processing . DOI: DOI: 10.1081/E-ECHP-120017565.
  • 27 Liu YQ. Li LH. Yang L. Li HY. Chem. Pap. 2010; 64: 533
  • 28 Meciarova M. Polackova V. Toma S. Chem. Pap. 2002; 56: 208
  • 29 Meciarova M. Toma S. Babiak P. Chem. Pap. 2004; 58: 104
  • 30 Tabatabaeian K. Mamaghani M. Mahmoodi NO. Khorshidi A. Catal. Commun. 2008; 9: 416
    • 31a Kumar V. Sharma A. Sharma M. Sharma UK. Sinha AK. Tetrahedron 2007; 63: 9718
    • 31b Sinha AK. Sharma A. Joshi BP. Tetrahedron 2007; 63: 960
    • 32a Sharma N. Chundawat TS. Bhagat S. Synthesis 2016; 48: 4495
    • 32b Chundawat TS. Sharma N. Kumari P. Bhagat S. Synlett 2016; 27: 404
    • 32c Chundawat TS. Sharma N. Kumari P. Bhagat S. Med. Chem. Res. 2016; 25: 2335
  • 33 Conventional method for the synthesis of 9H-pyrido[3,4-b]indole-3-carboxamide derivatives (3a–k); General procedure: To a stirred solution of 1 (1 equiv) in DMF were added EDC·HCl (1.1 equiv) and HOBt (1.1 equiv), followed by addition of DIPEA (2.1 equiv). The resulting reaction mixture was stirred at r.t. for 30 minutes. The requisite amine 2ac was added portionwise and the reaction was stirred at r.t. for 15–18 h (Table 1). Progress of reaction was monitored by TLC. After completion, the reaction mixture was poured into ice-cold water, and the precipitate filtered. Column chromatography on silica (100–200 mesh), eluting with 30–40% ethyl acetate/hexane gave the pure 1-acetyl-3-carboxamide-β-carboline derivatives 3ac.Ultrasound method for the synthesis of 1-acetyl-3-carboxamide-β-carboline derivatives (3a–k); General procedure: To a stirred solution of 1 (1equiv) in DMF were added EDC·HCl (1.1 equiv) and HOBt (1.1 equiv), followed by addition of DIPEA (2.1 equiv). The resulting reaction mixture was stirred at r.t. for 10 minutes. The requisite amine 2ak was added portionwise and the reaction was stirred at r.t. under sonication for the time detailed in Table 1 and Table 2. The progress of the reaction was monitored by TLC. After completion, the reaction mixture was poured into ice-cold water, and the precipitate filtered. Column chromatography on silica (100–200 mesh), eluting with 30–40% ethyl acetate/hexane gave the pure 1-acetyl-3-carboxamide-β-carboline derivatives 3ak.Representative Spectroscopic Data1-Acetyl-N-phenethyl-9H-pyrido[3,4-b]indole-3-carboxamide (3a): Pale-yellow solid; mp 172–174 °C; IR (KBr): 3349, 2914, 1683, 1534 cm–1; 1H NMR (400 MHz, CDCl3): δ = 10.31 (s, 1 H, -NH), 9.00 (s, 1 H), 8.12 (d, J = 7.63 Hz, 1 H), 8.00 (t, 1 H, -NH), 7.56–7.50 (m, 2 H), 7.31–7.18 (m, 6 H), 3.78 (q, J = 6.78 Hz, 2 H), 2.93 (t, J = 6.78 Hz, 2 H), 2.67 (s, 3 H); 13C NMR (100 MHz, CDCl3): δ = 202.2, 164.4, 141.4, 139.1, 139.0, 136.1, 133.4, 132.5, 129.6, 128.8, 128.7, 126.5, 122.2, 121.4, 120.9, 118.2, 112.1, 40.4, 35.8, 25.6; HRMS (ESI): m/z [M+H]+ calcd for C22H19N3O2: 358.1555; found: 358.1545.1-Acetyl-N-(2,4-difluorophenyl)-9H-pyrido[3,4-b]indole-3-carboxamide (3j): Yellow solid; mp 210–212 °C; IR (KBr): 3350, 2916, 1665, 1539 cm–1; 1H NMR (400 MHz, DMSO-d 6): δ = 12.29 (s, 1 H, -NH), 10.39 (s, 1 H, -NH), 9.19 (s, 1 H), 8.12 (q, J = 6.10 Hz, 1 H), 7.83 (d, J = 7.63 Hz, 1 H), 7.63 (t, J = 8.39 Hz, 1 H), 7.46–7.41 (m, 1 H), 7.34 (t, J = 7.63 Hz, 1 H), 7.17 (t, J = 8.39 Hz, 1 H), 2.93 (s, 3 H); 13C NMR (100 MHz, CDCl3): δ = 200.6, 162.5, 145.1, 142.9, 142.4, 137.2, 135.0, 133.9, 133.9, 132.2, 129.5, 122.4, 121.0, 120.2, 118.4, 113.4, 111.4, 104.5, 104.2, 25.9; HRMS (ESI): m/z [M+H]+ calcd for C20H13F2N3O2: 366.1054; found: 366.1061
  • 34 Huang H. Yao Y. He Z. Yang T. Ma J. Tian X. Li Y. Huang C. Chen X. Li W. Zhang S. Zhang C. Ju J. J. Nat. Prod. 2011; 74: 2122
  • 35 Tang J.-G. Liu H. Zhou Z.-Y. Liu J.-K. Synth. Commun. 2010; 40: 1411