1430
R. Zamora, F. J. Hidalgo
LETTER
Table 1 Yields of Isolated Pyrroles Prepared in this Studya
References and Notes
(1) (a) Knorr, L. Ber. Dtsch. Chem. Ges. 1884, 17, 1635.
(b) Paal, C. Ber. Dtsch. Chem. Ges. 1885, 18, 367.
(c) Banik, B. K.; Samajdar, S.; Banik, I. J. Org. Chem. 2004,
69, 213. (d) Banik, B. K.; Banik, I.; Renteria, M.; Dasgupta,
S. K. Tetrahedon Lett. 2005, 46, 2643. (e) Werner, S.; Iyer,
P. S. Synlett 2005, 1405.
(2) (a) Hidalgo, F. J.; Zamora, R. J. Biol. Chem. 1993, 268,
16190. (b) Hidalgo, F. J.; Zamora, R. J. Lipid Res. 1995, 36,
725. (c) Lee, S. H.; Oe, T.; Blair, I. A. Chem. Res. Toxicol.
2002, 15, 300. (d) Zamora, R.; Hidalgo, F. J. Chem. Res.
Toxicol. 2003, 16, 1632. (e) Zamora, R.; Hidalgo, F. J.
Chem. Res. Toxicol. 2005, 18, 342.
(3) (a) Sayre, L. M.; Arora, P. K.; Iyer, R. S.; Salomon, R. G.
Chem. Res. Toxicol. 1993, 6, 19. (b) Sayre, L. M.; Sha, W.;
Xu, G.; Kaur, K.; Nadkarni, D.; Subbanagounder, G.;
Salomon, R. G. Chem. Res. Toxicol. 1996, 9, 1194.
(c) Amarnath, V.; Valentine, W. N.; Montine, T. J.;
Patterson, W. H.; Amarnath, K.; Basset, C. N.; Grahan, D. G.
Chem. Res. Toxicol. 1998, 11, 317. (d) Liu, Z.; Minkler, P.
E.; Sayre, L. M. Chem. Res. Toxicol. 2003, 16, 901.
(4) (a) Buu-Hoi, N. P.; Xuong, N. D. J. Org. Chem. 1955, 20,
850. (b) Danks, T. N. Tetrahedron Lett. 1999, 40, 3957.
(c) Quiclet-Sire, B.; Quintero, L.; Sanchez-Jimenez, G.;
Zard, S. Z. Synlett 2003, 75. (d) Wang, B.; Gu, Y.; Luo, C.;
Yang, T.; Yang, L.; Suo, J. Tetrahedron Lett. 2004, 45,
3417.
(5) (a) Katritzky, A. R.; Karelson, M.; Malhotra, N.
Heterocycles 1991, 32, 127. (b) Nyulaszi, L.; Varnai, P.;
Veszpremi, T. J. Mol. Struct. (THEOCHEM) 1995, 358, 55.
(6) Reactions were carried out by heating at 110 °C under an
inert atmosphere, the pyrrole (0.1 mmol) in 3 mL of 0.3 M
sodium citrate buffer (pH 3), and in the presence, or not, of
the amine (0.1 mmol). The pyrroles produced were extracted
three times with CHCl3–MeOH (3:2) and purified by TLC.
Identity of purified compounds was confirmed by 1H NMR,
13C NMR and MS.
Yield (%)
(1:1)b (1:2)b
Compound R1
R2
H
R5
H
1
2
CH3(CH2)3
1
2
3
5
CH3(CH2)3
PhCH2
Me
H
Me
H
3
1
3
4
PhCH2
Me
H
Me
H
24
4
34
5
5
2-MeC6H4
2-MeC6H4
4-MeC6H4
4-MeC6H4
4-MeOC6H4
4-MeOC6H4
2-Me-4-MeOC6H3
6
Me
H
Me
H
52
3
55
5
7
8
Me
H
Me
H
53
2
99
5
9
10
11
12
13
14
Me
H
Me
H
66
2
98
4
2-Me-4-MeOC6H3 Me
Me
H
81
1
99
3
2-Me-6-MeC6H3
2-Me-6-MeC6H3
H
Me
Me
42
65
a R1, R2, and R5 are the substituents at positions 1, 2, and 5, respec-
tively, of the pyrrole ring. Pyrroles with R2 = R5 = H were obtained
from 1H-pyrrole. Pyrroles with R2 = R5 = CH3 were obtained from
2,5-dimethyl-1H-pyrrole. Reaction scheme is given in Scheme 1.
b Pyrrole/amine ratio.
macromolecules. Furthermore, during in vitro and in vivo
of both Maillard reaction and lipid oxidation, different
pyrrole motifs are produced by reaction of carbohydrates
and oxidized lipids with the terminal amino groups of pro-
teins.8 These protein-bound pyrroles are believed to inhib-
it protease action9 and to produce a change of protein
charge that has been related, for example, to macrophage
receptor recognition of oxidatively damaged low density
lipoproteins as a primary or secondary event in atherogen-
esis.10 The analysis of bound pyrroles is difficult because
they are usually destroyed during the acid hydrolysis of
proteins and there is not a certainty of their structures.11
The new reaction described in this study can be employed
to develop new analytical procedures for the characteriza-
tion and determination of these products.
(7) Hargis, D. C.; Shubkin, R. L. Tetrahedron Lett. 1990, 31,
2991.
(8) (a) Ledl, F.; Schleicher, E. Angew. Chem., Int. Ed. Engl.
1990, 19, 565. (b) Hidalgo, F. J.; Zamora, R. Chem. Res.
Toxicol. 2000, 13, 501. (c) Salomon, R. G.; Kaur, K.;
Podrez, E.; Hoff, H. F.; Krushinsky, A. V.; Sayre, L. M.
Chem. Res. Toxicol. 2000, 13, 557. (d) Hidalgo, F. J.;
Zamora, R. Ann. N.Y. Acad. Sci. 2005, 1043, 319.
(9) (a) Zamora, R.; Hidalgo, F. J. J. Agric. Food Chem. 2001,
48, 6006. (b) Powell, S. R.; Wang, P.; Divald, A.; Teichberg,
S.; Haridas, V.; McCloskey, T. W.; Davies, K. J. A.;
Hartzeff, H. Free Radical Biol. Med. 2005, 38, 1093.
(10) (a) Steinbrecher, U. P.; Lougheed, M.; Kwan, W. C.; Dirks,
M. J. Biol. Chem. 1989, 264, 15216. (b) Podrez, E. A.;
Hoppe, G.; O’Neil, J.; Sayre, L. M.; Sheibani, N.; Hoff, H.
F. J. Lipid Res. 2000, 41, 1455. (c) Stocker, R.; Keaney, J.
F. Jr. Physiol. Rev. 2004, 84, 1381.
(11) (a) Hidalgo, F. J.; Alaiz, M.; Zamora, R. Anal. Biochem.
1998, 262, 129. (b) Gu, X.; Meer, S. G.; Miyagi, M.;
Rayborn, M. E.; Hollyfield, J. G.; Crabb, J. W.; Salomon, R.
G. J. Biol. Chem. 2003, 278, 42027. (c) Hidalgo, F. J.;
Nogales, F.; Zamora, R. Anal. Biochem. 2004, 334, 155.
Acknowledgment
This study was supported in part by the European Union (FEDER
funds) and the Plan Nacional de I+D of the Ministerio de Educación
y Ciencia of Spain (Project AGL2003-02280). We are indebted to
J. L. Navarro for technical assistance.
Synlett 2006, No. 9, 1428–1430 © Thieme Stuttgart · New York