4760
A. M. Piloto et al. / Tetrahedron Letters 46 (2005) 4757–4760
0
0
0
0
0
8
0 ꢁC. After cooling, the reaction mixture was acidified
126.90 (C-4 ), 128.11 (C-3 , C-5 ), 128.54 (C-2 , C-6 ),
0
with aqueous 6 M hydrochloric acid solution until
pH = 5–6. The mixture was extracted with ethyl acetate
129.42 (C-5b), 130.48 (C-6), 134.95 (C-1 ), 142.75 (C-
2), 154.47 (C-3a), 158.76 (C-8), 169.83 (CONH),
171.42 (CO CH ). FTIR (KBr disc) 3284, 1750, 1662,
(
3 · 10 mL), the organic extracts were combined, dried
2
3
ꢀ
1625 cm . HRMS: m/z (EI) calcd for C H NO
25 23 5
1
with magnesium sulphate and evaporated under vacuum
in a rotary evaporator to yield a brownish solid, which
was recrystallised from ethyl acetate/n-hexane. 8-Meth-
oxy-naphtho[2,1-b]furan-1-yl acetic acid 2c was
417.1576, found 4171588.
obtained as a brown solid (0.188 g, 98%). Mp 176.8–
1
Acknowledgements
1
78.9 ꢁC. R = 0.31 (ethyl acetate). H NMR (DMSO-
f
d , 300 MHz) d 3.90 (s, 3H, OCH ), 4.04 (s, 2H, CH ),
Thanks are due to the Foundation for Science and Tech-
nology (Portugal) for financial support through Centro
de Qu ´ı mica (UM).
6
3
2
7
.14 (dd, 1H, J = 9.0 and 2.5 Hz, H-7), 7.56 (s, 1H, H-
), 7.58 (d, 1H, J = 9.0 Hz, H-5), 7.75 (d, 1H,
9
J = 9.0 Hz, H-4), 7.93 (d, 1H, J = 9.0 Hz, H-6), 7.96 (s,
1
H, H-2), 12.4 (br s, 1H, OH). C NMR (DMSO-d6,
5.4 MHz) d 31.03 (CH ), 55.06 (OCH ), 102.99 (C-9),
10.09 (C-5), 115.74 (C-1), 115.87 (C-7), 120.52 (C-3b),
25.21 (C-5a), 125.45 (C-4), 129.13 (C-5b), 130.41 (C-
), 143.20 (C-2), 153.22 (C-3a), 157.78 (C-8), 172.62
3
1
7
1
1
6
2
3
References and notes
1. Goel, A.; Dixit, M. Tetrahedron Lett. 2004, 45, 8819–8821,
and references cited therein.
2
3
4
5
. Hovius, R.; Vallotton, P.; Wohland, T.; Vogel, H. Trends
Pharmacol. Sci. 2000, 21, 266–273.
. Berthelot, T.; La ¨ı n, G.; Latxague, L.; D e´ leris, G. J.
Fluoresc. 2004, 14, 671–675.
. Haj-Yehia, A. I.; Benet, L. Z. J. Chromatogr. B 1995, 666,
45–53.
. Saito, M.; Ushijima, T.; Sasamoto, K.; Ohkura, Y.; Ueno,
K. J. Chromatogr. B 1995, 674, 167–175.
(
1
4
C@O). FTIR (KBr disc) 3442, 3103, 3016, 1703,
ꢀ
627 cm . Anal. Calcd for C H O : C, 70.30; H,
15 12 4
1
.72. Found: C, 70.52; H, 4.82.
2.3. General experimental procedure for the synthesis of
labelled L-amino acids 4, 6 and 8 (described for 4e)
Compound 2c (95 mg, 0.371 mmol) was reacted with L-
phenylalanine methyl ester hydrochloride (96 mg,
6. Saito, M.; Ushijima, T.; Sasamoto, K.; Yakata, K.;
Ohkura, Y.; Ueno, K. Anal. Chim. Acta 1995, 300, 243–
251.
0
.45 mmol) in DMF (2 mL) by a standard DCC/HOBt
7
8
9
. Gon c¸ alves, M. S. T.; Maia, H. L. S. Tetrahedron Lett.
001, 42, 7775–7777.
. Gon c¸ alves, M. S. T.; Maia, H. L. S. Org. Biomol. Chem.
003, 1, 1480–1485.
. Fraga, S. M. B.; Gon c¸ alves, M. S. T.; Moura, J. C. V. P.;
Rani, K. Eur. J. Org. Chem. 2004, 1750–1760.
coupling. After dry chromatography on silica gel (ethyl
acetate/n-hexane, 4:6) and recrystallisation from ethyl
acetate/n-hexane, N-[2-(8-methoxy-naphtho[2,1-b]furan-
2
2
1
obtained as a white solid (0.112 g, 72%). Mp 146.3–
-yl)-acetyl] phenylalanine methyl ester 4e was
1
1
48.4 ꢁC, R = 0.38 (ethyl acetate/n-hexane, 4:6).
H
f
10. Batista, R. M. F.; Costa, S. P. G.; Raposo, M. M. M.
Tetrahedron Lett. 2004, 45, 2825–2828.
NMR (CDCl , 300 MHz) 3.55–3.81 (m, 2H, b-CH
3
2
Phe), 3.57 (s, 3H, CO CH ), 3.93 (s, 3H, OCH ), 3.96
(
11. Furuta, T.; Wang, S. S.-H.; Dantzker, J. L.; Dore, T. M.;
Bybee, W. J.; Callaway, E. M.; Denk, W.; Tsien, R. Y.
Proc. Natl. Acad. Sci. U.S.A. 1999, 96, 1193–1200.
2
3
3
s, 2H, CH ), 4.60–4.80 (m, 1H, a-CH Phe), 6.05 (d,
2
0
H, J = 8.1 Hz, NH), 6.47 (d, 2H, J = 7.5 Hz, H-2
1
and H-6 ), 6.79 (t, 2H, J = 7.5 Hz, H-3 and H-5 ),
0
0
0
1
2. 9,10-Diphenylanthracene was excited at the wavelengths
of maximum emission found for each one of the com-
pounds to be tested; Morris, J. V.; Mahaney, M. A.;
Huber, J. R. J. Phys. Chem. 1976, 80, 969–974.
0
6.96 (t, 1H, J = 7.5 Hz, H-4 ), 7.14 (dd, 1H, J = 9.0
and 2.1 Hz, H-7), 7.48 (d, 1H, J = 2.1 Hz, H-9), 7.52
(
J = 9.0 Hz, H-5), 7.85 (d, 1H, J = 9.0 Hz, H-6).
d, 1H, J = 9 Hz, H-4), 7.62 (s, 1H, H-2), 7.73 (d, 1H,
C
1
3. Grehn, L.; Gunnarson, K.; Ragnarsson, U. Acta Chem.
Scand., Ser. B 1987, 41, 18–23.
1
3
NMR (CDCl , 75.4 MHz) 34.00 (CH ), 37.61 (b-CH
3
2
2
14. Maia, H. L. S.; Monteiro, L. S.; Sebasti a˜ o, J. Eur. J. Org.
Chem. 2001, 1967–1970.
Phe), 52.20 (CO CH ), 52.93 (a-CH Phe), 55.62
2
3
(
1
OCH ) 102.31 (C-9), 110.04 (C-4), 115.03 (C-1),
16.86 (C-7), 120.04 (C-3b), 125.61 (C-5a), 126.30 (C-5),
15. Bodanszky, M.; Bodanszky, A. The Practice of Peptide
Synthesis; Springer: Berlin, 1984.
3