490
T. S. Chinta Rao et al. / Tetrahedron Letters 54 (2013) 487–490
mixture was refluxed for 16 h. The progress of the reaction was monitored by
TLC. The reaction mixture was cooled and concentrated under reduced
pressure. The residue was crystallized in acetone (ꢀ100 ml) to give the
desired quaternary ammonium salt.
entries are also available) associated with this article can be found,
22. Preparation of sempervirine (5): To a stirred solution of 2 (6.0 g, 17.2 mmol) in
methanol, 1,2-cyclohexanedione (2.5 g, 22.3 mM) and sodium methoxide
(3.6 g, 66.9 mmol) were added at room temperature. The resulting reaction
mixture was stirred in CEM-Microwave (Power-150 W, Pressure-250 psi) at
95 °C for 1 h after which it was cooled and acidified with dilute acetic acid. The
mixture was concentrated, and the obtained residue was purified by flash
column chromatography over silica-gel (230–400 mesh) using 0–10% MeOH in
DCM as eluent, to afford 2.4 g (53% yield) of as yellow solid. 1HNMR (DMSO-d6,
400 MHz): d 1.90 (m, 4H), 3.01 (m, 2H), 3.17 (m, 2H), 7.43 (t, 1H, J = 10 Hz),
7.67 (t, 1H, J = 10 Hz), 7.83 (d, 1H, J = 10.8 Hz), 8.38 (1H, d, J = 10.8 Hz), 8.68
(1H, d, J = 9.2 Hz), 8.76 (bs, 1H), 8.86 (1H, d, J = 9.2 Hz), 13.17 (bs, 1H). 13C NMR
(CD3OD, 100 MHz) d: 22.7, 22.8, 27.4, 30.4, 113.5, 116.9, 120.4, 122.5, 122.2,
123.0, 127.1, 130.3, 130.9, 132.2135.0, 135.9, 142.5, 151.4; MS (m/z): 273.18
(100%), 274.19 (13%); mp: 270–271 °C [Lit: 258–260 °C]14; UV kmax(MeOH):
388, 337, 295, 242 nm.
References and notes
1. (a) Prelog, V. Helv. Chim. Acta 1948, 31, 588–593; (b) Schwarz, H.; Marion, L.
Can. J. Chem. 1953, 31, 958–975; (c) Woodward, R. B.; Witkop, B. J. Am. Chem.
Soc. 1949, 71, 379; (d) Bentley, R.; Stevens, T. S. Nature 1949, 141–142.
2. Beljanski, M.; Beljanski, M. S. IRCS Med. Sci. 1984, 12, 587–588.
3. Beljanski, M.; Beljanski, M. S. Exp. Cell Biol. 1982, 50, 79–87.
4. Bassleer, R.; Clermont, D.; Marnette, J. M.; Caprasse, M.; Tits, M.; Angenot, L.
Ann. Pharm. Fr. 1985, 43, 83–88.
5. Beljanski, M.; Bugiel, J. Fr. Demande. FR 2419725, 1979.
6. Honda, R.; Tanaka, H.; Yasuda, H. FEBS lett. 1997, 420, 25–27.
7. Sasiela, C. A.; Stewart, D. H.; Kitagaki, J.; Safiran, Y. J.; Yang, Y.; Weissman, A.;
Oberoi, P.; Davydov, I. V., et al J. Biomol. Screening 2008, 13, 229–237.
8. Matlashewski, G.; Lamb, P.; Pim, D.; Peacock, J.; Crawford, L.; Benchimol, S.
EMBO J. 1984, 3, 3257–3262.
23. Preparation of sempervirine nitrate (6): To a suspension of (1.5 g, 5.5 mmol) in
methanol (10 ml), 6 N HCl (7.0 ml) was added at room temperature. The
resulting clear solution was stirred for 2 h, and then concentrated to dryness.
The residue was dissolved in methanol (10 ml); a solution of sodium nitrate
(10 ml) was added to it. A solid precipitated out after some time. It was stirred
for 2 h and filtered. The solid was washed with water, and air dried to yield
1.4 g of sempervirine nitrate as greenish yellow solid. 1HNMR (DMSO-d6,
400 MHz): d 1.90 (m, 4H), 3.02 (m, 2H), 3.18 (m, 2H), 7.44 (t, 1H, J = 10 Hz),
7.68 (t, 1H, J = 9.6 Hz), 7.83 (d, 1H, J = 10.8 Hz), 8.39 (1H, d, J = 10.8 Hz), 8.69
(1H, d, J = 8.4 Hz), 8.86 (1H, d, J = 9.2 Hz), 9.27 (1H, bs), 13.17 (1H, bs). MS (m/
z): 273.05 (100%), 274.06 (13%). HRMS: 273.1370 which corresponds to
[C19H17N2]+; IR (cmÀ1): 3400, 2937, 1646, 1632, 1524, 1469, 1383. mp: 280.5–
9. Peters, J. M.; Franke, W. W.; Kleinschmidt, J. A. J. Biol. Chem. 1994, 269, 7709–
7718.
10. Dickens, P.; Fitzgerald, R.; Fischer, P. M. Semin. Cancer Biol. 2010, 20, 10–18.
11. Zhizhen, Z.; Ping, W.; Wei, Y.; Shiyou, L. Plantamedica 2008, 74, 1818–1822.
12. Woodward, R. B.; McLamore, W. M. J. Am. Chem. Soc. 1949, 71, 379–380.
13. (a) Lipin´ ska, T. M. Tetrahedron 2006, 62, 5736–5747; (b) Lipin´ ska, T. M.;
Rykowski, A. Synth. Commun. 1996, 26, 4409–4414.
14. Chatterjee, A.; Sahu, A.; Saha, M.; Bannerji, J. Monatsh. Chem. 1996, 127, 1259–
1262.
15. (a) Gribble, G. W.; Barden, T. C.; Johnson, D. A. Tetrahedron 1988, 44, 3195–
3202; (b) Gribble, G. W.; Johnson, D. A. Tetrahedron Lett. 1987, 28, 5259–
5262.
16. Potts, K. T.; Mattingly, G. S. J. Org. Chem. 1968, 33, 3985–3987.
17. Ban, Y.; Seo, M. Tetrahedron 1961, 16, 11–15.
18. Swan, G. A. J. Chem. Soc. 1958, 2038–2044.
19. Westphal, O.; Jahn, K.; Heffe, W. Arch. Pharm. 1961, 294, 37–45.
20. One reaction was done following the conditions described in the following
reference: Matiaa, M. P.; Ezquerrab, J.; Garcia-Navfoa, J. L.; Vaqueroa, J. J.;
Alvarez-Builla, J. Tetrahedron Lett. 1991, 32, 7575–7578.
282.1 °C [Lit: 267 °C, decomp]18 13C NMR (DMSO-d6, 100 MHz) d: 21.1, 21.1,
;
25.7, 28.7, 112.5, 115.7, 118.9, 120.4, 120.7, 121.4, 121.5, 125.7, 128.6, 129.2,
130.0, 132.7, 134.5, 140.4, 148.9.
24. General procedure: To a solution of quanternary ammonium bromide derivative
(1.0 mmol) in methanol, the diketo compound (1.2 mmol, 1.2 equiv) and
sodium methoxide (4.0 mmol, 4.0 equiv) were added at room temperature. The
resulting reaction mixture was heated in CEM-Microwave (Explorer) between
95 °C and 105 °C (Power 150 W and Pressure 250 psi) temperature for 50 min.
The reaction mixture was acidified with acetic acid and concentrated under
reduced pressure. The crude product was purified by column chromatography
over a silica-gel eluting with a mixture of methanol and dichloroemethane.
21. General procedure for quaternization: To
a solution of the heterocycle
(10.0 mmol) in ethanol (20 ml) or in acetone (20 mL), ethyl bromoacetate
(15.0 mmol, 1.5 equiv) was added at room temperature. The resulting reaction