3-Alkylpyridinium Salts from the Marine Sponge Pachychalina sp.
0
1
.45 mmol, 2.5 equiv.) in a dry mixture of toluene/Et
0 mL) was added imidazole (48 mg, 0.72 mmol, 4 equiv.). The
2
O (1:2,
(5 mL) was added acetyl chloride (50 µL, 0.4 mmol, 20 equiv.), and
the solution was stirred at room temperature for 24 h. The solvent
removal gave 10 mg of pure pachychaline A (1) (100%)
mixture was stirred under an inert atmosphere until total dissol-
ution of the reactants. Iodine (87 mg, 0.34 mmol, 2 equiv.) was then
added, and the reaction mixture was stirred at room temperature
for 2 h. After the addition of few drops of triethylamine, the solu-
tion was diluted with CH
washed with a saturated aqueous solution of NaHCO
The organic layer was then dried with MgSO , filtered and concen-
Supporting Information (see footnote on the first page of this arti-
cle): NMR and MS spectra of pachychalines A (1), B (2) and C
1
13
(
3). H and C NMR spectroscopic data for compounds 4 to 8.
2
Cl
2
(30 mL), and the organic layer was
3
(2ϫ50 mL).
4
Acknowledgments
trated. The resulting residue was purified by silica gel flash
chromatography using a solvent system gradient (50 mL of each
We are grateful to PharmaMar Madrid for biological screenings
and for financial support also provided by a grant (R. L.) of the
Provence-Alpes-Côte d’Azur Region and the CNRS. We also thank
J. Vacelet and T. Perez for careful taxonomical sponge identifica-
tion and M. Gaysinski for assistance in recording the NMR spec-
troscopic experiments. We finally thank Mr le préfet de la Marti-
nique and the DIREN for their help in the collection of Caribbean
marine invertebrates.
solvent: cyclohexane, cyclohexane/CH
yield 67 mg of the pure compound 7 (68%). H NMR (200 MHz,
CDCl ): δ = 1.20–1.76 (m, 44 H), 1.74 (quint, J = 7.2 Hz, 2 H),
.17 (t, J = 7.0 Hz, 2 H), 3.53 (t, J = 7.5 Hz, 2H 2 rotamers) ppm.
2 2 2 2
Cl , 50:50 and CH Cl ) to
1
3
3
13
C NMR (75 MHz, CDCl
3
): δ = 82.0, 46.7, 33.7, 30.6, 29.8, 29.7,
29.6, 29.5, 29.2, 28.7, 28.2, 26.9, 7.5 ppm. IR (neat): ν˜ = 2978, 2920,
2
–1
851, 1788, 1753, 1720, 1695, 1675, 1630 cm .
3,3Ј-(Dodecan-1,12-diyl)bis(pyridine) (8): To a solution of 3-iodo-
pyridine (205 mg, 1 mmol, 2 equiv.), palladium acetate (22.4 mg,
0
2
.1 mmol, 0.2 equiv.), tetrabutylamonium chloride (556 mg, [1] For reviews on 3-alkylpyridinium salts, see: a) K. Sepcik, J.
Toxicol., Toxin Rev. 2000, 19, 139–160; b) R. J. Andersen,
R. W. van Soest, F. Kong, “Alkaloids” in Chemical and Bio-
logical Perspectives (Eds.: S. W. Pelletier), Pergamon, Elsevier
Science, Oxford, 1996, vol. 10, pp. 301–355.
3
mmol, 4 equiv.) and NaHCO (84.0 mg, 0.1 mmol, 2 equiv.) in
dry DMF (5 mL) was added dodeca-1,11-diene (83 mg, 0.5 mmol,
equiv.). The solution was stirred at 115 °C for 17 h. The reaction
mixture was diluted in Et O (25 mL) and washed with brine
2ϫ30 mL). The combined organic layer was dried with MgSO
filtered and concentrated. Purification by silica gel flash
chromatography (MeOH/CH Cl , 5:95) afforded 50 mg of a mix-
1
2
[
[
2] K. Sepcik, T. Turk, Prog. Mol. Subcell. Biol. 2006, 42, 105–
(
4
,
124.
3] a) N. Fusetani, N. Asai, S. Matsunaga, Tetrahedron Lett. 1994,
23, 3967–3970; b) J. H. H. L. De Oliveira, A. Grube, M. Köck,
R. G. S. Berlinck, M. L. Macedo, A. G. Ferreira, E. Hajdu, J.
Nat. Prod. 2004, 67, 1685–1689.
4] C. A. Volk, M. Köck, Org. Lett. 2003, 5, 3567–3569.
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Prod. 2006, 69, 135–137.
6] J. H. H. L. Oliveira, M. H. R. Seleghim, C. Timm, A. Grube,
M. Köck, G. G. F. Nascimento, A. C. T. Martins, E. G. O.
Silva, A. O. Souza, P. R. R. Minarini, F. C. S. Galetti, C. L.
Silva, E. Hajdu, R. G. S. Berlinck, Mar. Drugs 2006, 4, 1–8.
2
2
ture of saturated and unsaturated analogues of 8 (by NMR analy-
sis). The residue was then dissolved in EtOAc (5 mL) and Pd/C
[
[
(
8 mg) was added. The reaction mixture was vigorously stirred un-
der H at atmospheric pressure for 6 h. Filtration through a thick
pad of Celite (EtOAc) yielded 50 mg of pure bispyridine 8 (overall
2
[
1
yield 35%). H NMR (200 MHz, CDCl
3
): δ = 1.10–1.40 (m, 16 H),
1
.56 (quint, J = 6.9 Hz, 4 H), 2.55 (t, J = 7.9 Hz, 4 H), 7.18 (dd, J
=
7.5, 4.6 Hz, 2 H), 7.46 (dt, J = 7.7, 1.5 Hz, 2 H), 8.34 (m, 4 H)
13
ppm. C NMR (75 MHz, CDCl
3
): δ = 158.3, 150.0, 147.2, 135.9,
[7] J. H. H. L. Oliveira, A. M. Nascimento, M. H. Kossuga, B. C.
Cavalcanti, C. O. Pessoa, M. O. Moraes, M. L. Macedo, A. G.
Ferreira, E. Hajdu, U. S. Pinheiro, R. G. S. Berlinck, J. Nat.
Prod. 2007, 70, 538–543.
1
2
23.3, 33.1, 31.2, 29.7, 29.6, 29.5, 29.3 ppm. IR (neat): ν˜ = 2925,
–
1
–1
–1
853, 1654 cm . UV (MeOH): λmax (ε, cm ) = 269 (3500), 263
+
(
[
3
4900), 257 (4400) nm. MS (ESI+): m/z = 347.3 [M + Na] , 325.3
M + H] . HRMS (ESI+): calcd. for C22
+
+
[8] R. Talpir, A. Rudi, M. Ilan, Y. Kashman, Tetrahedron Lett.
H
33
N
2
325.2644; found
1
992, 21, 3033–3034.
9] A. Grube, C. Timm, M. Köck, Eur. J. Org. Chem. 2006, 1285–
295.
25.2655.
[
3
,3Ј-(Dodecane-1,12-diyl)bis(1-{16-[bis(tert-butoxycarbonyl)amino]-
1
hexadecyl}pyridinium) Diiodide: A solution of 7 (52 mg, 0.09 mmol, [10] C. Timm, M. Köck, Synthesis 2006, 15, 2580–2584 and refer-
3
equiv.) and 8 (10 mg, 0.03 mmol, 1 equiv.) in CH
stirred under reflux for 72 h. After concentration of the reaction
mixture, the residue was purified by reverse-phase HPLC (C18
3
CN (5 mL) was
ences cited therein; A. Kaiser, C. Marazano, M. Maier, J. Org.
Chem. 1999, 64, 3778–3782.
11] F. Liang, S. Wan, Z. Li, X. Xiong, L. Yang, X. Zhou, C. Wu,
Curr. Med. Chem. 2006, 13, 711–727.
[12] K. S. Moore, S. Wherli, H. Roder, M. Rogers, J. N. Forrest Jr,
[
,
Luna, 150ϫ4.6 mm, 5 µm, 100% MeOH) to give 32 mg of tet-
1
raBoc protected pachychaline A (1) (88%). H NMR (200 MHz,
D. McCrimmon, M. Zasloff, Proc. Natl. Acad. Sc. USA 1993,
3
CD OD): δ = 1.25–1.44 (m, 36 H), 1.50 (s, 36 H), 1.74 (m, 4 H),
.00 (m, 4 H), 2.89 (t, J = 7.8 Hz, 4 H), 3.56 (t, J = 7.5 Hz, 4 H),
90, 1354–1358.
2
4
[
13] D. E. Williams, P. Lassota, R. J. Andersen, J. Org. Chem. 1998,
.62 (t, J = 7.5 Hz, 4 H), 8.02 (dd, J = 7.7, 6.0 Hz, 2 H), 8.46 (d,
6
3, 4838–4841; D. E. Williams, K. S. Craig, B. Patrick, L. M.
1
3
J = 7.9 Hz, 2 H), 8.86 (d, J = 5.8 Hz, 2 H), 8.98 (s, 2 H) ppm.
C
McHardy, R. van Soest, M. Roberge, R. J. Andersen, J. Org.
Chem. 2002, 67, 245–258.
3
NMR (200 MHz, CD OD): δ = 154.1, 146.7, 145.7, 128.9, 83.5,
6
2
1
2.9, 33.5, 32.5, 31.6, 30.7, 30.6, 30.5, 30.4, 30.3, 30.1, 30.0, 28.8,
[14] N. Ushio-Sata, S. Matsunaga, N. Fusetani, K. Honda, K. Yas-
umuro, Tetrahedron Lett. 1996, 37, 225–228.
[15] J. E. Baldwin, R. C. Whitehead, Tetrahedron Lett. 1992, 33,
2059–2062.
8.3, 27.7, 27.1 ppm. IR (neat): ν˜ = 2977, 2921, 2854, 1771, 1732,
–1
–1
–1
698, 1682, 1633 cm . UV (MeOH): λmax (ε, cm ) = 267 (8800)
2+
2+
nm. MS (ESI+): m/z = 602.5 [M] , 552.5 [M – Boc] , 502.4 [M –
[
16] A. Kaiser, X. Billot, A. Gateau-Olesker, C. Marazano, B. C.
Das, J. Am. Chem. Soc. 1998, 120, 8026–8034.
Received: August 10, 2007
2
Boc]2+
.
Synthetic Pachychaline A (1): To a solution of the tetraBoc pro-
tected pachychaline A (25 mg, 0.02 mmol, 1 equiv.) in MeOH
Published Online: November 2, 2007
Eur. J. Org. Chem. 2008, 121–125
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
125