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Synlett 2015; 26(14): 1969-1972
DOI: 10.1055/s-0034-1381043
letter
© Georg Thieme Verlag Stuttgart · New York

Synthesis and Molecular Docking Study of Novel Chromeno-chromenones as Anti-HIV-1 NNRT Inhibitors

Hanmant M. Kasralikar
Department of Chemistry, Dnyanopasak College, Parbhani-431 401, MS, India   Email: bhusare71@yahoo.com
,
Suresh C. Jadhavar
Department of Chemistry, Dnyanopasak College, Parbhani-431 401, MS, India   Email: bhusare71@yahoo.com
,
Sudhakar R. Bhusare*
Department of Chemistry, Dnyanopasak College, Parbhani-431 401, MS, India   Email: bhusare71@yahoo.com
› Author Affiliations
Further Information

Publication History

Received: 26 April 2015

Accepted after revision: 09 June 2015

Publication Date:
06 August 2015 (online)

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Abstract

l-Proline has been employed efficiently for the synthesis of chromeno-chromenone derivatives via a one-pot, three component condensation reaction of salicylaldehydes, 4-hydroxy coumarin, and indole or barbituric acid. The simple procedure and good to excellent yields (78–90%) are notable features of the method. The obtained derivatives were studied for their molecular docking as an anti-HIV-1 RT.

Keywords

chromeno-chromenone - salicylaldehyde - 4-hydroxycoumarin - l-proline - anti-HIV activity - molecular docking

Supporting Information

    Supporting information for this article is available online at http://dx.doi.org/10.1055/s-0034-1381043. Included are the experimental details and details for the molecular docking studies.
  • Supporting Information
 

  • References and Notes

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  • 32 General Procedure for the Synthesis of Chromeno-chromenone Derivatives A mixture of salicylaldehyde (1 mmol), 4-hydroxycoumarin (1 mmol), and l-proline (0.1 mmol) in EtOH (5 mL) was heated to reflux for 6 h. Indole or barbituric acid (1 mmol) was then added to the reaction mixture and reflux continued with stirring for a further 6–8 h (monitoring by TLC). The solid formed was filtered washed with EtOH then with H2O to afford analytically pure product.
  • 33 Representative Analytical Data 9,11-Dibromo-7-(1H-indol-3-yl)-6H,7H-chromeno[4,3-b]chromen-6-one (4c) Brownish solid; yield 90%; mp (280 °C). IR: 3410, 2900, 2350, 2300, 1700, 1600, 1550, 1450, 1400, 1300, 1210, 1150,900, 750, 700 cm–1. 1H NMR (300 MHz, CDCl3): δ = 10.29 (s 1 H, NH), 8.23 (d, 1 H), 8.03 (d, 1 H), 7.67 (t, 2 H), 7.48 (m, 3 H), 7.32 (t, 1 H), 7.21 (d, 2 H), 5.31 (s, 1 H). 13C NMR (300 MHz, CDCl3): δ = 164.53, 158.62, 151.25, 149.00, 147.63, 141.00, 140.87, 135.00, 133.39, 132.52, 130.43, 25.55, 125.06, 124.62, 124.25, 123.87, 117.93, 117.13, 116.57, 111.82, 105.03, 104.00, 103.80, 30.47 cm–1. GC–MS: m/z = 523 [M+]. 9-Bromo-11-iodo-7-(1H-indol-3-yl)-6H,7H-chromeno[4,3-b]chromen-6-one (4g) Brownish solid; yield 85%; mp (282 °C). IR: 3300, 2910, 2870, 1700, 1610, 1490, 1395, 1210, 1050, 850, 820, 710, 600 cm–1. 1H NMR (300 MHz, CDCl3): δ = 10.38 (s, 1 H, NH), 8.14 (dd, 1 H), 8.02 (dd, 1 H), 7.65 (m, 1 H), 7.55 (m, 1 H), 7.52 (m, 1 H), 7.49 (m, 1 H), 7.41 (m, 2 H), 7.34 (d, 1 H), 7.24 (s, 1 H), 7.12 (s, 1 H). 13C NMR (300 MHz, CDCl3): δ = 166.00, 157.12, 153.00, 149.00, 146.00, 143.50, 136.00, 135.39, 134.42, 130.52, 126.85, 125.06, 124.32, 124.25, 124.00, 117.91, 117.12, 116.51, 111.00, 106.00, 101.52, 100.00, 31.00. GC–MS: m/z = 570 [M+]. 5-{9-Chloro-6-oxo-6H,7H-chromeno[4,3-b]chromen-7-yl}-6-hydroxypyrimidine-2,4-(1H,3H)-dione (4m) Brownish solid; yield 89%; mp (89 °C). IR: 3600, 3420, 3380, 2996, 2817, 1702, 1663, 1611, 1566, 1452, 1400, 1215, 1168, 786, 530 cm–1. 1H NMR (400 MHz, DMSO): δ = 12.87 (s, 1 H, OH), 9.89 (s, 1 H, NH), 8.04 (d, 1 H), 7.85 (s, 1 H), 7.60 (s, 1 H), 7.49 (t, 1 H), 7.29 (t, 2 H), 7.18 (d, 1 H), 6.81 (s, 1 H, NH), 5.73 (s, 1 H). 13C NMR (300 MHz, CDCl3): δ = 167.08, 165.76, 163.80, 161.00, 154.29, 152.42, 150.80, 132.36, 131.10, 129.00, 127.63, 127.23, 125.72, 125.12, 120.00, 117.49, 117.12, 115.12, 110.00, 81.50, 29.24. GC–MS: m/z = 410 [M+].