M. A. Ameur Meziane et al. / Tetrahedron Letters 42 (2001) 1017–1020
1019
OH
EWG
NH2
i
EWG
O
O
O
N
EWG
N
- H O
2
1b
EWG = CO2Et, CN
10(b,d)
11(b,d)
EWG
N
-
H O
2
7
b (EWG = CO Et) : 75%
2
7d (EWG = CN) : 40%
Scheme 3. Reagents and conditions: (i) EtONa 2 equiv., dry EtOH, D, N , MgSO , 4 h.
2
4
Acknowledgements
J. Am. Chem. Soc. 1948, 70, 180; (b) Saxena, A. K.; Jain,
P. C.; Anand, N. Indian J. Chem. 1975, 13, 230.
. Cain, M.; Weber, R. W.; Guzman, F.; Cook, J. M.; Barker,
S. A.; Rice, K. C.; Crawley, J. N.; Paul, S. M.; Skolnick,
P. J. Med. Chem. 1982, 25, 1081.
8
One of us (M. A. Ameur Meziane) wishes to thank
Merck Eurolab, Prolabo div. (Fr) for a research fellow-
ship. The authors thank also Professor Jack Hamelin
for fruitful discussions.
9. (a) Shamma, M.; Moniot, J. L. In Isoquinoline Alkaloid
Research, 1972–1977; Plenum Press: New York, 1978; pp.
6–7; (b) Pommeranz, C. Monatshefte 1893, 14, 116; (c)
Fritsch, P. Chem. Ber. 1893, 26, 419; (d) Gensler, W. Org.
React. 1951, 6, 191; (e) Miller, R. B.; Frincke, J. M. J. Org.
Chem. 1980, 45, 5312.
References
1
2
. Biagani, S. C. G.; North, M. In Amino Acids, Peptides and
Proteins Specialist Periodicals Reports; Davies, J. S., Ed.;
The Royal Society of Chemistry: London, 1996; Vol. 27,
Chapter 3.
. (a) Kyle, D. J.; Martin, J. A.; Farmer, S. G.; Birch, R. M.
J. Med. Chem. 1991, 34, 1230; (b) Klutchko, S.; Blankley,
C. J.; Fleming, R. W.; Hinckley, J. M.; Werner, A. E.;
Nordin, J.; Holmes, A.; Hoefle, M. L.; Cohen, D. M. J.
Med. Chem. 1986, 29, 1953; (c) Steinbaugh, B. A.; Hamil-
ton, H. V.; Patt, W. C.; Rapundalo, S. T.; Batley, B. L.;
Lunney, E. A.; Ryan, M. J.; Hicks, G. W. Bioorg. Med.
Chem. Lett. 1994, 4, 2029; (d) Kazmierski, W.; Hruby, V.
J. Tetrahedron 1988, 44, 697.
10. Moustaid, K.; Nguyen, D. A.; Laude, B.; Mercier, M. F.;
Sedqui, A. Can. J. Chem. 1992, 70, 802.
11. Lerestif, J. M.; Feuillet, S.; Bazureau, J. P.; Hamelin, J. J.
Chem. Res. (S) 1999, 32.
12. (a) Lerestif, J. M.; Toupet, L.; Sinbandhit, S.; Tonnard, F.;
Bazureau, J. P.; Hamelin, J. Tetrahedron 1997, 53, 6351;
(b) Lerestif, J. M.; Bazureau, J. P.; Hamelin, J. Synlett
1995, 647.
13. (a) 4,5-Dimethoxy phthalaldehyde 1a is readily available
from veratric acid in a three-step sequence involving the
intermediate lactone m-meconine. (b) 3-Methoxy phthal-
aldehyde 1c is prepared with the same sequence from
m-anisic acid.
3. Dyke, S. F. Adv. Heterocycl. Chem. 1972, 14, 279.
O
MeO
MeO
CO H
i
i
i
MeO
MeO
iii
MeO
MeO
CHO
CHO
2
MeO
MeO
OH
OH
O
8
9%
85%
98%
2
veratric acid
m-meconine
1a
Reagents and conditions: (i) HCHO 37%, dry HCl, 15˚C, 8 h then 30˚C, 12 h, NH OH. (ii) LiAlH , dry THF, ∆, 4 h.
4
4
(
iii) MnO , CH Cl , 25˚C, 24 h.
2
2 2
4
. (a) Bazureau, J. P.; Le Roux, J.; Le Corre, M. Tetrahedron
Lett. 1988, 29, 1921; (b) Czombos, J.; Aelterman, W.;
Tkachev, A.; Martins, J. C.; Tourwe, D.; Peter, A.; Toth,
G.; F u¨ l o¨ p, F.; De Kimpe, N. J. Org. Chem. 2000, 65, 5469;
See: Dopp, F. D.; Battacharjee, D. J. Heterocycl. Chem.
1980, 17, 315; Barfield, M.; Spear, R. J.; Sternhell, S. J. Am.
Chem. Soc. 1975, 97, 5160; Edwards, G. A.; Perkin, W. H.;
Stoyle, F. W. J. Chem. Soc. 1925, 195.
(
1
c) Murphy, P. J.; Lee, E. L. J. Chem. Soc., Perkin Trans.
1999, 3049.
14. Compound 8 was obtained by treatment of commercial
diethyl aminomalonate hydrochloride (30 g, 0.14 mol) with
saturated sodium hydrogenocarbonate (225 ml) in methyl-
ene chloride (300 ml) during 20 min. After drying the
5
. (a) Grethe, G. In The Chemistry of Heterocyclic Com-
pounds; Wiley: New York, 1981; Vol. 38, Part 1; (b)
Kametani, T. In The Total Synthesis of Natural Products;
Apsimon, J., Ed.; Wiley: New York, 1977; Vol. 3, pp. 4–34.
. Pictet–Spengler cyclization, see: Ref. 5a; 5b, pp. 34–58.
. (a) Julian, P. L.; Karpel, J.; Moghani, A.; Meyer, E. W.
organic layer over MgSO and elimination of solvent, 8
4
(22.6 g, 91%) was stored under an inert atmosphere at 4°C.
1
6
7
H NMR (CDCl , 200 MHz, TMS) l 1.30 (t, 3H, J=7 Hz);
3
2.08 (br. s, 2H, NH); 4.25 (q, 2H, J=7 Hz); 4.18 (s, 1H).