[ Pobierz całość w formacie PDF ]
the organic phase washed with H2O(2 10 mL), sat. NaHCO3 (10 mL),
dried (Na2SO4) and the solvent evaporated. The residue was purified by
flash chromatography (AcOEt/Et. Petr. ¼ 2:8, Rf ¼ 0.43) to afford pure 3d
(0.50 g, 2.4 mmol, 65%), characterized as follows: white solid, m.p. 57 C
1
(CH3OH); H NMR 1.29 (6H, d, J ¼ 6.9 Hz, CH3), 3.66 (1H, ept,
J ¼ 7.2 Hz, CH), 3.87 (6H, s, OCH3), 7.05 (2H, s, HAr), 9.89 (1H, s,
13
CHO); C NMR 20.0, 24.5, 55.7, 105.4, 131.8, 135.0, 158.9, 191.9;
IR 1685, 1580 cm 1. Anal. calcd. for C12H16O3: C 69.20; H 7.76. Found:
C 69.08; H 7.85.
(E )-1,3-Dimethoxy-2-(1-methylethyl)-5-(2-phenylethenyl)benzene (4b):
NaH (2.8 mmol, 0.11 g of a 60% dispersion in mineral oil) was placed
under dry Ar in a two-necked flask equipped with reflux condenser and
magnetic stirrer, washed with anhydrous THF (3 5 mL) and suspended
in anhydrous THF (10 mL) containing 15-crown-5 (15 mg). The mixture
was chilled to 0 C and a solution of diethyl benzylphosphonate (0.64 g,
0.6 mL, 2.7 mmol) and 3d (0.50 g, 2.4 mmol) in THF (5 mL) was added
dropwise. The mixture was stirred at r.t. overnight and quenched by slow
dropwise addition of H2O (10 mL). Et2O was added (20 mL), the organic
phase was separated, and the aqueous phase extracted with Et2O
(2 20 mL). The organic phase was washed with H2O (20 mL), dried
(Na2SO4), and the solvent evaporated. The residue was purified by flash
chromatography (AcOEt/Et. Petr. ¼ 1:9, Rf ¼ 0.44) to afford pure 4b
(0.53 g, 1.9 mmol, 78%), characterized as follows: colorless oil, which
1
solidifies upon standing, m.p. 66 68 C (lit.[7] m.p. 65 66 C); H NMR
1.29 (6H, d, J ¼ 7.2 Hz, 2 CH3), 3.60 (1H, ept, J ¼ 7.2 Hz, CH), 3.84 (6H,
s, CH3O), 6.69 (2H, s, ArH), 7.05 (2H, s, CH), 7.21 7.28 (1H, m, ArH),
13
7.30 7.38 (2H, m, ArH), 7.47 7.54 (2H, m, ArH); CNMR 20.7,
24.1, 55.7, 102.8, 124.4, 126.4, 127.5, 127.9, 128.6, 129.0,
135.8, 137.3, 158.7; IR ¼ 1580, 1570 cm 1.
MARCEL DEKKER, INC. " 270 MADISON AVENUE " NEW YORK, NY 10016
©2003 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
1316 Azzena, Vittoria Idini, and Pilo
ACKNOWLEDGMENT
Financial support from the University of Sassari (ex 60% funds) is
gratefully acknowledged.
REFERENCES
1. Cushman, M.; Nagarathnam, D.; Gopal, D.; Chakraborti, A.K.;
Lin, C.M.; Hamel, E. J. Med. Chem. 1991, 34, 2579 2588 and
references therein.
2. Thakkar, K.; Geahlen, R.L.; Cushman, M. J. Med. Chem. 1993, 36,
2950 2955.
3. Treadwell, E.M.; Cermak, S.C.; Wiemer, D.F. J. Org. Chem. 1999,
64, 8718 8723 and references therein.
4. Likhitwitayawuid, K.; Sritularak, B.; De-Eknamkul, W. Planta
Med. 2000, 66, 275 277.
5. Ahn, K.-S.; Kim, J.-H.; Oh, S.-R.; Ryu, S.-Y.; Lee, H.-K. Planta
Med. 2000, 66, 641 644.
6. Shimizu, K.; Fukuda, M.; Kondo, R.; Sakai, K. Planta Med. 2000,
66, 16 19.
7. Krow, G.R.; Miles, W.H.; Smiley, P.M.; Lester, W.S.; Kim, Y.J.
J. Org. Chem. 1992, 57, 4040 4043 and references therein.
´
8. Alonso, E.; Ramon, D.J.; Yus, M. J. Org. Chem. 1997, 62, 417 421.
9. Kim, S.-H.; Rieke, R.D. J. Org. Chem. 2000, 65, 2322 2330.
10. Azzena, U.; Denurra, T.; Melloni, G.; Rassu, G. Synthesis 1989,
28 30.
11. Azzena, U.; Cossu, S.; Denurra, T.; Melloni, G.; Piroddi, A.M.
Synthesis 1990, 313 314.
12. Azzena, U.; Denurra, T.; Melloni, G.; Piroddi, A.M. J. Org. Chem.
1990, 55, 5386 5390.
13. Azzena, U.; Melloni, G.; Piroddi, A.M.; Azara, E.; Contini, S.;
Fenude, E. J. Org. Chem. 1992, 57, 3101 3106.
14. Baker, R.; Sims, R. J. Synthesis 1981, 117.
15. Sajiki, H.; Hattori, K.; Hirota, K. J. Org. Chem. 1998, 63,
7990 7992.
16. Russell, T.W.; Duncan, D.M.; Hansen, S.C. J. Org. Chem. 1977,
42, 551 552.
17. As an alternative, reaction of benzaldehyde 3c with PhCH2MgCl in
Et2O (81%), followed by catalytic hydrogenation of the C C double
bond (5% Pd/C, EtOH, 90%) and dehydration (DMSO, reflux,
28%), afforded stilbene 4b with an overall lower yield.
MARCEL DEKKER, INC. " 270 MADISON AVENUE " NEW YORK, NY 10016
©2003 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
Antibiotic Stilbenes by Reductive Metalation 1317
18. Kompis, I.; Then, R.; Boehni, E.; Rey-Bellet, G.; Zanetti, G.;
Mantovan, M. Eur. J. Med. Chem. Chim. Ter. 1980, 15, 17 22.
Received in the USA April 1, 2002
MARCEL DEKKER, INC. " 270 MADISON AVENUE " NEW YORK, NY 10016
©2003 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
[ Pobierz całość w formacie PDF ]