(E)-Hept-3-ene-1,3,7-tricarbaldehyde (15)
dd, J = 11.9, 6.0 Hz, H-4); 13C-NMR (100 MHz; CDCl3) d 195.0
=
(HC O), 154.3 (C-2), 142.0 (C-1), 30.2 (C-3), 20.8 ppm (C-4); IR:
Colorless oil; Rf 0.2 (C6H12–EtOAc 1 : 1); MS (ESI) m/z 183
u
max(film):, 1675 cm-1; HRMS m/z calcd for C10H12O2Na 187.0735
1
[M+H]+; H-NMR (400 MHz; CDCl3) d 9.79 (1H, s, H-3¢), 9.72
[M+Na]+; found 187.0737.
(1H, s, H-7), 9.35 (1H, s, H-1), 6.48 (1H, t, J = 7.4 Hz, H-3),
2.59-2.49 (6H, m, 2 H-2¢, 2 H-1¢, 2 H-6), 2.44 (2H, q, J = 7,4 Hz,
2 H-4), 1.83 ppm (2H, qu, J = 7.4 Hz, 2 H-5); 13C-NMR (100
MHz; CDCl3) d 201.2(C-7), 200.8 (C-3¢), 194.2 (C-1), 154.3 (C-3),
141.7 (C-2), 42.6 (C-6), 41.7 (C-2¢), 27.6 (C-4), 20.4 (C-5), 16.4
ppm (C-1¢); IR: umax(film): 1725, 1685 cm-1.
Notes and references
1 R. A. Azevedo and P. J. Lea, Amino Acids, 2001, 20, 261–279.
2 See for example: (a) W. M. Golebiewski and I. D. Spenser, Can. J.
Chem., 1985, 63, 2707–2718; (b) W. M. Golebiewski and I. D. Spenser,
J. Am. Chem. Soc., 1984, 106, 7925–7927.
3 See among many others: A. M. Brown, D. J. Robins, L. Witte and M.
Wink, Plant Physiol. (Life Sci. Adv.), 1991, 10, 179–185 and references
cited therein.
4 One needs to keep in mind that in the plants, reactive functional groups
such as aldehydes will most likely be masked in a transitory way. In this
article, in order to simplify schemes and figures, these functional groups
will be shown in their reactive form. In the case of glutaraldehyde, it is
a known protein-reticulating agent and its presence as a free molecule
in a living cell is of course unlikely but we will see that equivalents in
terms of oxidation state can be put forward (vide infra).
5 (a) E. Gravel, E. Poupon and R. Hocquemiller, Org. Lett., 2005, 7,
2497–2499; (b) E. Gravel, E. Poupon and R. Hocquemiller, Tetrahedron,
2006, 62, 5248–5253; (c) R. Salame, E. Gravel, K. Leblanc and E.
Poupon, Org. Lett., 2009, 11, 1891–1894; (d) E. Gravel and E. Poupon,
Nat. Prod. Rep., 2010, 27, 32–56.
6 (a) M. J. Wanner and G. J. Koomen, in Studies in Natural Products-
Chemistry: Stereoselectivity in Synthesis and Biosynthesis of Lupine and
Nitraria Alkaloids, ed. Atta-ur-Rahman, Elsevier, Amsterdam, 1994;
vol. 14, pp 731–768 and references therein; (b) M. J. Wanner and G.
J. Koomen, J. Org. Chem., 1994, 59, 7479–7484; (c) M. J. Wanner and
G. J. Koomen, J. Org. Chem., 1995, 60, 5634–5637; (d) D. Franc¸ois,
M.-C. Lallemand, M. Selkti, A. Tomas, N. Kunesch and H.-P. Husson,
J. Org. Chem., 1997, 62, 8914–8916; (e) D. Franc¸ois, M.-C. Lallemand,
M. Selkti, A. Tomas, N. Kunesch and H.-P. Husson, Angew. Chem.,
Int. Ed., 1998, 37, 104–105.
7 See for example: (a) V. C. Pham, A. Jossang, T. Se´venet, V. H. Nguyen
and B. Bodo, Tetrahedron, 2007, 63, 11244–11249; (b) V. C. Pham, A.
Jossang, T. Se´venet, V. H. Nguyen and B. Bodo, Eur. J. Org. Chem.,
2009, 1412–1416 and references cited therein. See also, ref. 5d.
8 Glutaraldehyde 2 is quite stable as an aqueous solution whereas
it undergoes rapid polymerization in neat conditions with catalytic
amount of water. The numerous applications of 2 have been extensively
reviewed over the years as a cross-linking agent in biochemistry or
histology or as a biocide: see among others, Types of Antimicro-
bials Agents, in Russel, Hugo & Ayliffe’s Principle and Practice of
Disinfection, Preservation and Sterilization, ed. A. P. Fraise, P. A.
Lambert and J.-Y. Maillard, 4th edn, Blackwell Publishing, Oxford,
2004, pp. 8–97; M. A. Hayat, Glutaraldehyde, in Principles and
Techniques of Electron Microscopy, Biological Applications, Cambridge
University Press, Cambridge, 2000, pp. 28–42; H.-P. Husson, J. Royer,
Glutaraldehyde, in e-EROS Encyclopedia of Reagents for Organic
Synthesis, John Wiley & Sons, Chichester, 2001.
9 See inter alia: (a) P. M. Hardy, A. C. Nicholls and H. N. Rydon, J. Chem.
Soc., Chem. Commun., 1969, 565–566; (b) T. Tashima, U. Kawakami,
M. Harada, T. Sakata, N. Satoh, T. Nakagawa and H. Tanaka, Chem.
Pharm. Bull., 1987, 35, 4169–4180; (c) G. Goissis, S. A. Yoshioka, D.
M. Braile and V. D. A. Ramirez, Artif. Organs, 1998, 22, 210–214.
10 T. Tashima, M. Imai, Y. Kuroda, S. Yagi and T. Nakagawa, J. Org.
Chem., 1991, 56, 694–697.
(E)-2-(5,5-Diethoxypentylidene)pentanedial (16)
Colorless oil; Rf 0.55 (C6H12–EtOAc 1 : 1); MS (ESI) m/z 257
1
[M+H]+; H-NMR (400 MHz; CDCl3) d 9.70 (1H, s, H-5), 9.32
(1H, s, H-1), 6.49 (1H, t, J = 7.4 Hz, H-1¢), 4.54 (1H, t, J = 5.3,
H-5¢), 3.65-3.55 (2H, m, CH2O), 3.50-3.40 (2H, m, CH2O), 2.50
(4H, s, 2 H-4, 2H-3), 2.38 (2H, q, J = 7.4 Hz, 2 H-2¢), 1.68-1.50
(4H, m, 2H-4¢, 2H-3¢), 1.16 ppm (6H, t, J = 7.0 Hz, 2 ¥ CH3);
13C-NMR (100 MHz; CDCl3) d 201.2 (C-5), 194.8 (C-1), 155.8
(C-1¢), 141.8 (C-2), 102.5 (C-5¢), 61.3 (CH2O), 61.1 (CH2O), 42.3
(C-4), 32.3 (C-4¢), 28.7 (C-2¢), 23.8 (C-3¢), 17.0 (C-3), 15.6 ppm
(2 ¥ CH3).
(E)-2-(3,3-Diethoxypropyl)hept-2-enedial (17)
Colorless oil; Rf 0.54 (C6H12–Et2O 8 : 2); MS (ESI) m/z 257
1
[M+H]+; H-NMR (400 MHz; CDCl3) d 9.76 (1H, s, H-7), 9.30
(1H, s, H-1), 6.43 (1H, t, J = 7.4 Hz, H-3), 4.40 (1H, t, J = 5.7,
H-3¢), 3.70-3.60 (2H, m, CH2O), 3.52-3.40 (2H, m, CH2O), 2,50
(2H, m, 2 H-6), 2.43 (2H, q, J = 7.4 Hz, 2 H-4), 2.25 (2H, m,
2H-1¢), 1.87 (2H, m, 2 H-5), 1.60 (2H, m, 2H-2¢), 1.22-1.10 ppm
(6H, m, 2 ¥ CH3); 13C-NMR (100 MHz; CDCl3) d 201.4 (C-7),
194.8 (C-1), 153.3 (C-3), 143.8 (C-2), 102.3 (C-3¢), 61.3 (CH2O),
61.1 (CH2O), 43.2 (C-6), 32.2 (C-2¢), 28.2 (C-4), 21.0 (C-5), 19.4
(C-1¢), 15.3 ppm (2 ¥ CH3); IR: umax(film): 1721, 1680 cm-1.
Protection of trialdehyde 15
Compound 15 (2 g, 11 mmol) was diluted in a mixture of CHCl3–
THF–EtOH, 10 : 3 : 0.1 (20 mL). The formation of 14, 16 and
17 was controlled by TLC (C6H12–EtOAc 1 : 1). After 6 h the
mixture was concentrated in vacuo. The residue was purified by
flash chromatography (C6H12–EtOAc 8 : 2), to give successively 14
(1.09 g, 30%), 16 (536 mg, 19%) and 17 (874 mg, 31%).
Reactivity of trialdehyde 15
Trialdehyde 15 (150 mg, 0.82 mmol) was dissolved in H2O (4 mL)
and basicified to pH 8.5 with NaHCO3. The basicified solution
was heated at 60 ◦C for 3 h, cooled to room temperature and
extracted with CH2Cl2 (3 ¥ 7 mL). The concentration under
reduced pressure of the dried (MgSO4) combined organic layers
gave a crude product that was purified by flash chromatography
(CH2Cl2–Et2O 9 : 1) to afford 18 (20 mg, 15%).
11 The yield is of course low, but experimentally speaking, glutaraldehyde
2 is a cheap reagent and 6 is the most nonpolar compound of the
reaction based on silica gel TLC profile which renders its purification
by chomatography easy. In practise, 15 g of 2 give 3–4 g of 6 in a
reproducible manner.
12 No information concerning the stereochemistry of 6 was disclosed in
ref. 10. A complete study is given for the first time in the present work..
13 Acetylation of 6 permitted the chromatographic resolution of A and B
resulting from the 2 major diastereomers of 6—see the ESI†.
(1E,5E)-Cycloocta-1,5-diene-1,5-dicarbaldehyde (18)
Colorless crystals; Rf 0.71 (CHCl3–EtOAc 1 : 1); MS (ESI) m/z 187
+
1
=
[M+23] ; H-NMR (400 MHz; CDCl3) d 9.36 (2H, s, HC O), 6.61
(2H, t, J = 4.9, H-2), 2.87 (4H, t, J = 6.6 Hz, H-3), 2.69 ppm (4H,
This journal is The Royal Society of Chemistry 2010
Org. Biomol. Chem., 2010, 8, 2522–2528 | 2527
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