D
Synlett
S. J. Johansson et al.
Letter
Funding Information
(10) (a) Hansen, H. S.; Moesgaard, B.; Hansen, H. H.; Petersen, G.
Chem. Phys. Lipids 2000, 108, 135. (b) Schmid, H. H. Chem. Phys.
Lipids 2000, 108, 71.
A postdoctoral scholarship for S.A. from the Department of Chemis-
try, the Norwegian University of Life Sciences, as well as funding from
the Research Council of Norway for a research scholarship to J.M.J.N.
and grants to Y.S. (NFR 209335 and NFR 244351) are gratefully ac-
knowledged. T.V.H. is grateful for financial support from the Research
Council of Norway (FRIPRO-FRINATEK 230470).()
(
11) (a) Coyne, L.; Lees, G.; Nicholson, R. A.; Zheng, J.; Neufield, K. D.
Br. J. Pharmacol. 2002, 135, 1977. (b) Huidobro-Toro, J. P.; Harris,
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B.; Carson, M. J.; Sutcliffe, J. G.; Thomas, E. A. Biochem. Pharma-
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(12) Maccarrone, M.; Pauselli, R.; di Rienzo, M.; Finazzi-Agrò, A. Bio-
chem. J. 2002, 366, 137.
Acknowledgment
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13) Rodriguez de Fonseca, F.; Navarro, M.; Gomez, R.; Escuredo, L.;
Nava, F.; Fu, J.; Murillo-Rodriguez, E.; Gluffrida, A.; Lo, Verme. J.;
Gaetani, S.; Kathurla, S.; Gall, C.; Piomell, D. Nature 2001, 414,
The authors are much indebted to Prof. Dag Ekeberg for performing
mass spectrometric analyses.
209.
(
(
(
14) Cravatt, B. F.; Prospero-Garcia, O.; Siuzdak, G.; Gilula, N. B.;
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Supporting Information
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Supporting information for this article is available online at
https://doi.org/10.1055/s-0037-1611939.
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References and Notes
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(21) General Procedure for Amide Coupling
To a stirred solution of the fatty acid (1.0 mmol, 1.0 equiv.) in
(
3
f) Mechoulam, R.; Fride, E.; Di Marzo, V. Eur. J. Pharmacol. 1998,
59, 1.
6) (a) Patel, D.; Witt, S. N. Oxid. Med. Cell. Longevity 2017, 2017, 18.
b) Rockenfeller, P.; Koska, M.; Pietrocola, F.; Minois, N.;
CH
After 30 min at room temperature, the amine (1.1 mmol, 1.1
equiv.) was added. After 12 h, CH Cl (25 mL) was added, fol-
lowed by saturated aqueous NH Cl. The mixture was acidified to
pH 2 by addition of HCl, the organic phase was separated, and
the aqueous layer was further extracted with CH Cl (3 × 10
2 2
Cl (5 mL) was added CDI (0.178 g, 1.1 mmol, 1.1 equiv.).
(
2
2
(
4
Knittelfelder, O.; Sica, V.; Franz, J.; Carmona-Gutierrez, D.;
Kroemer, G.; Madeo, F. Cell Death Differ. 2015, 22, 499. (c) Ohno-
Shosaku, T.; Tanimura, A.; Hashimotodani, Y.; Kano, M. Neuro-
scientist 2012, 18, 119.
2
2
mL). The organic phases were combined, dried over Na
SO , fil-
2
4
tered, and concentrated in vacuo, to give the amide.
(
7) (a) Coyne, L.; Lees, G.; Nicholson, R. A.; Zheng, J.; Neufield, K. D.
Br. J. Pharmacol. 2002, 135, 1977. (b) Huidobro-Toro, J. P.; Harris,
R. A. Proc. Natl. Acad. Sci. U.S.A. 1996, 93, 8078. (c) Hedlund, P.
B.; Carson, M. J.; Sutcliffe, J. G.; Thomas, E. A. Biochem. Pharma-
col. 1999, 58, 1807.
Example 1: (5Z,8Z,11Z,14Z,17Z)-N-[(R)-1-phenylethyl]icosa-
5,8,11,14,17-pentaenamide (R-28)
Starting with EPA (0.302 g, 1.0 mmol, 1.0 equiv.) and (R)--
methylbenzylamine (0.133 g, 0.14 mL, 1.1 mmol, 1.1 equiv.).
Yield 0.376 g, 93%; TLC (hexane/EtOAc 75:25, visualized by UV
2
0
1
(8) (a) Micale, V.; Mazzola, C.; Drago, F. Pharmacol. Res. 2007, 56,
and KMnO
(400 MHz, CDCl
3
4
stain): R
f
= 0.20; []
D
+5.2 (c = 0.2, MeOH). H NMR
382. (b) Pillarisetti, S.; Alexander, C. W.; Khanna, I. Drug Discov-
): = 7.49–7.06 (m, 5 H), 5.65 (d, J = 8.2 Hz, 1
ery Today 2009, 14, 1098.
9) (a) Burstein, S.; Salmonsen, R. Bioorg. Med. Chem. 2008, 16,
H), 5.47–5.27 (m, 10 H), 5.15 (p, J = 7.1 Hz, 1 H), 2.91–2.73 (m, 8
H), 2.18 (dd, J = 8.3, 6.6 Hz, 2 H), 2.15–2.02 (m, 4 H), 1.79–1.67
(m, 2 H), 1.50 (d, J = 6.9 Hz, 3 H), 0.98 (t, J = 7.5 Hz, 3 H). 13C NMR
(
9644. (b) Flygare, J.; Sander, B. Semin. Cancer Biol. 2008, 18, 176.
(
100 MHz, CDCl ): = 171.7, 143.2, 132.0, 129.1, 128.7 (2 × CH),
3
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Georg Thieme Verlag Stuttgart · New York — Synlett 2018, 29, A–E