8386
G. Cra6otto et al. / Tetrahedron Letters 44 (2003) 8383–8386
6. (a) Rigby, J. H.; Kondratenko, M. A. Bioorg. Med.
colour of DIAD immediately disappeared and a weakly
exothermic reaction occurred. The mixture was sonicated
for 35–55 min at 20°C. When the reaction was complete,
as indicated by TLC (eluant: n-hexane–ethyl acetate), the
mixture was evaporated. The residue was diluted with
hexane–ether 3:1, v/v, filtered through a thin pad of
Celite® to remove the precipitate of triphenylphosphine
oxide and concentrated under reduced pressure. Finally,
the products were purified by flash silica gel column
chromatography or by preparative HPLC. All the reac-
tions were carried out under nitrogen in a Teflon tube
(thickness 1 mm, diameter 35 mm, volume 40 mL)
inserted in the thermostatted reactor.
Chem. Lett. 2002, 12, 1829–1831; (b) Valerio, R. M.;
Bray, A. M.; Patsiouras, H. Tetrahedron Lett. 1996, 37,
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Chem. 2002, 67, 1754–1759.
9. Ko, S. Y. J. Org. Chem. 2002, 67, 2689–2691.
10. Cravotto, G.; Nano, G. M.; Palmisano, G.; Tagliapietra,
S. Heterocycles 2003, 60, 1351–1358.
11. Suzuki, E.; Katsuragawa, B.; Inoue, S. J. Chem. Res. (S)
1979, 110–111.
18. Pistelli, L.; Bertoli, A.; Bilia, A. R.; Morelli, I. Phyto-
chemistry 1996, 41, 1579–1582.
12. Cravotto, G.; Nano, G. M.; Palmisano, G.; Tagliapietra,
S. Synthesis 2003, 8, 1286–1291.
19. Harayama, T.; Katsuno, K.; Yoshitaka, N.; Fuji, M.;
Abe, H.; Takeuchi, Y. Heterocycles 2001, 54, 319–328.
20. (a) Singh, M. M.; Gupta, D. N.; Wadhwa, V.; Jain, G.
K.; Khanna, N. M.; Kamboj, V. P. Planta Med. 1985, 3,
268–270; (b) Prakash, A. O.; Pathak, S.; Shaiv, A.;
Mathur, R. Phytother. Res. 1994, 8, 28–32; (c) Prakash,
A. O.; Sharma, M. Phytother. Res. 1997, 11, 1–5.
13. (a) Minassi, A.; Tron, G. C.; Daddario, N.; Bianchi, F.;
Cravotto, G.; Bertolino, A.; Appendino, G. XXVII
Conv. Naz. S.C.I. Trieste 09/2001, Abs. P125; (b)
Cravotto, G.; Appendino, G.; Balliano, G. XXVIII
Conv. Naz. S.C.I., Roma, 09/2002, Abs. P95.
14. Appendino, G.; Minassi, A.; Tron, G. C.; Daddario, N.;
Bianchi, F. Org. Lett. 2002, 4, 3839–3841.
21. Eiden, A.; Buchecker, R.; Kjosen, H.; Liaaen-Jensen, S.
15. Important applications for the alkylation of the phenolic
hydroxyl of the coumarin core have been described in the
preparation of novobiocin derivatives (Jenneret, V.;
Vogel, P.; Renaut, P.; Millet, J.; Theveniaux, J.; Barber-
ousse, V. Bioorg. Med. Chem. Lett. 1998, 8, 1687–1688)
and of aryl coumarin-based inhibitors of gyrase B
(Everett, S. A.; Swann, E.; Naylor, M. A.; Stratford, M.
R. L.; Patel, K. B.; Tian, N.; Newman, R. G.; Vojnovic,
B.; Moody, C. J.; Wardman, P. Biochem. Pharmacol.
2002, 63, 1629–1639).
16. Cravotto, G.; Omiccioli, G.; Vazzoler, E. Patent PN
2003-A000032. Our sonochemical apparatus, developed
in collaboration with TEKIMP srl (Castelfranco Veneto,
TV, Italy) and designed for stringent reaction conditions,
consists of a transducer built with pre-pressed piezoelec-
tric ceramic rings that can be tuned between the frequen-
cies of 18 and 45 kHz. It is equipped with a dynamic
probe that, when in operation, can be made to move
alternatively up and down at a chosen speed. The probe
system (comprising the transducer, the booster and an
immersion horn) can work in continuous mode for many
hours thanks to an efficient cooling system. The probe is
refrigerated by an oil forced-circulation circuit that con-
veys heat to an oil-freon heat exchanger; this in turn is
cooled by a chiller. A regulation console monitors all
relevant parameters. To achieve optimal acoustic
efficiency all reactions are carried out in Teflon tubes (1
mm thick). For a rapid and efficient cooling the reactor is
thermostatted using four Peltier modules.
Acta Chem. Scand. B 1975, 29, 1015–1023.
22. Isoferujol: 7-[(3,7-dimethyl-2-octenyl)oxy]-8-hydroxy-2H-
1-benzopyran-2-one (14a): white powder; mp 56–58°C;
IR (KBr) 3255, 1738, 1713, 1692, 1607 and 1051 cm−1; 1H
NMR (400 MHz, CDCl3) l 7.62 (d, 1H, 3J=9.5 Hz,
3
3
H-4), 6.97 (d, 1H, J=8.6 Hz, H-5), 6.85 (d, 1H, J=8.6
3
Hz, H-6), 6.39 (br s, 1H, OH), 6.25 (d, 1H, J=9.5 Hz,
H-3), 5.47 (tq, 1H, 3J=6.7 and 4J=1.3 Hz, H-2%), 4.70 (d,
2H, 3J=6.7 Hz, H-1%), 2.04 (t, 2H, 3J=7.6 Hz, H-4%), 1.73
(d, 3H, 4J=1.3 Hz, 3%-Me), 1.52 (nonuplet, 1H, 3J=6.6
Hz, H-7%), 1.46–1.37 (m, 2H, H-6%), 1.19–1.09 (m, 2H,
H-5%), 0.86 (d, 6H, 3J=6.6 Hz, 2×7%-Me); CIMS: 317
(M+H)+. Anal. calcd for C19H24O4: C, 72.13; H, 7.65.
Found: C, 72.16; H, 7.62.
Ferujol: 8-[(3,7-dimethyl-2-octenyl)oxy]-7-hydroxy-2H-1-
benzopyran-2-one (14b): white powder; mp 68–70°C
[lit.20a 68–70°C]; IR (KBr) 3410, 1735, 1705, 1601 and
1
1125 cm−1; H NMR (400 MHz, CDCl3) l 7.62 (d, 1H,
3
3J=9.6 Hz, H-4), 7.09 (d, 1H, J=8.5 Hz, H-5), 6.87 (d,
3
1H, J=8.5 Hz, H-6), 6.34 (br s, 1H, OH), 6.23 (d, 1H,
3
4
3J=9.6 Hz, H-3), 5.47 (tq, 1H, J=7.6 and J=1.0 Hz,
3
3
H-2%), 4.84 (d, 2H, J=7.6 Hz, H-1%), 1.97 (t, 2H, J=7.6
Hz, H-4%), 1.64 (d, 3H, 4J=1.3 Hz, 3%-Me), 1.49 (nonu-
plet, 1H, 3J=6.6 Hz, H-7%), 1.40–1.24 (m, 2H, H-6%),
1.12–1.00 (m, 2H, H-5%), 0.84 (d, 6H, 3J=6.6 Hz, 2×7%-
Me); CIMS: 317 (M+H)+. Anal. calcd for C19H24O4: C,
72.13; H, 7.65. Found: C, 72.15; H, 7.63.
23. (a) Chang, C. T.; Doong, S. L.; Tsai, I. L.; Chen, I. S.
Phytochemistry 1997, 45, 1419–1422; (b) Tsai, I. L.; Lin,
W. Y.; Teng, C. M.; Ishikawa, T.; Doong, S. L.; Huang,
M. W.; Chen, Y. C.; Chen, I. S. Planta Med. 2000, 66,
618–623; (c) Curini, M.; Epifano, F.; Maltese, F.; Marco-
tullio, M. C.; Gonzales, S. P.; Rodriguez, J. C. Aust. J.
Chem. 2003, 56, 59–60.
17. General conditions for the Mitsunobu reaction. A solution
in anhydrous THF containing triphenylphosphine (1
equiv.), the alcohol (1 equiv.) and the dihydroxycoumarin
was sonicated at 10°C under an argon atmosphere (18.0
kHz, 380 W). Diisopropyl azodicarboxylate (DIAD) (1
equiv.) was added dropwise over 5 min. The orange-red