M
S. Jung et al.
Paper
Synthesis
1H NMR (400 MHz, DMSO-d6): = 0.85 (t, J = 7.0 Hz, 3 H, CH3(CH2)14),
1.24–1.27 (m, 24 H, CH3(CH2)12), 1.53–1.57 (m, 2 H, CH2CH2CO), 2.22
(t, J = 7.4 Hz, 2 H, CH2CO), 6.66, 7.34 (d, d, J = 8.9, 8.9 Hz, 2 H, 2 H,
C6H4), 9.10 (s, 1 H, NHCO), 9.55 (s, 1 H, OH).
13C NMR (100 MHz, DMSO-d6): = 13.8, 22.0, 25.2, 28.6, 28.7, 28.8,
28.9, 28.9, 31.2, 114.9, 120.8, 130.9, 153.0, 170.5.
1H NMR (400 MHz, DMSO-d6): = 0.85 (t, J = 6.9 Hz, 3 H, CH3(CH2)7),
1.23–1.27 (m, 20 H, CH3(CH2)6, (CH2)4 CH2CH2CO), 1.53–1.57 (m, 2 H,
CH2CH2CO), 1.93–1.94 (m, 4 H, 2 × CH2CH), 2.22 (t, J = 7.4 Hz, 2 H,
CH2CO), 5.35–5.37 (m, 2 H, 2 × CH), 6.66, 7.34 (d, d, J = 8.9, 8.9 Hz, 2 H,
2 H, C6H4), 9.10 (s, 1 H, NHCO), 9.55 (s, 1 H, OH).
13C NMR (100 MHz, DMSO-d6): = 13.9, 22.0, 25.1, 28.3, 28.4, 28.6,
28.6, 28.7, 28.9, 31.2, 31.9, 114.6, 120.7, 130.0, 130.0, 131.0, 153.0,
170.4.
HRMS (ESI-TOF): m/z [M + Na]+ calcd for C22H37NO2Na: 370.2717;
found: 370.2760.
HRMS (ESI-TOF): m/z [M + Na]+ calcd for C24H39NO2Na: 396.2873;
found: 396.2899.
N-(4-Hydroxyphenyl)oleamide (9cm)
Yield: 147 mg (79%); colorless powder; mp 99–100 °C.
(5Z,8Z,11Z,14Z)-N-(4-Hydroxyphenyl)arachidonamide (AM404;
IR (KBr): 3278 (NH), 1649 (CON) cm–1
.
9gm)4
1H NMR (400 MHz, CDCl3): = 0.88 (t, J = 6.9 Hz, 3 H, CH3(CH2)7),
1.27–1.32 (m, 20 H, CH3(CH2)6, (CH2)4CH2CH2CO), 1.68–175 (m, 2 H,
CH2CH2CO), 2.00–2.02 (m, 4 H, 2 × CH2CH), 2.33 (t, J = 7.6 Hz, 2 H,
CH2CO), 5.33–5.36 (m, 2 H, 2 × CH), 5.50 (br s, 1 H, NHCO), 6.76, 7.29
(d, d, J = 8.8, 8.7 Hz, 2 H, 2 H, C6H4), 7.06 (br s, 1 H, OH).
13C NMR (100 MHz, CDCl3): = 14.1, 22.7, 25.7, 27.2, 27.3, 29.2, 29.3,
29.3, 29.3, 29.5, 29.7, 29.8, 31.9, 37.6, 115.8, 122.6, 129.8, 130.0,
130.4, 153.1, 171.8.
Yield: 124 mg (90%); colorless powder; mp 51–52 °C.
IR (KBr): 3315 (NH), 1653 (CON) cm–1
.
1H NMR (400 MHz, CDCl3): = 0.88 (t, J = 6.9 Hz, 3 H, CH3(CH2)4),
1.25–1.39 (m, 6 H, CH3(CH2)3), 1.77–1.85 (m, 2 H, CH2CH2CO), 2.02–
2.08 (m, 2 H, CH3(CH2)3CH2), 2.14–2.18 (m, 2 H, CH2(CH2)2CO), 2.34 (t,
J = 7.6 Hz, 2 H, CH2CO), 2.79–2.84 (m, 6 H, 3 × CHCH2CH), 5.30–5.44
(m, 8 H, 8 × CH), 6.17 (br s, 1 H, NHCO), 6.74, 7.25 (d, d, J = 8.8, 7.4 Hz,
2 H, 2 H, C6H4), 7.15 (s, 1 H, OH).
13C NMR (100 MHz, CDCl3): = 14.1, 22.6, 25.4, 25.7, 26.6, 27.2, 29.3,
31.5, 36.8, 115.8, 122.6, 127.5, 127.9, 128.1, 128.3, 128.6, 129.0, 130.2,
130.6, 153.2, 171.6.
HRMS (ESI-TOF): m/z [M + Na]+ calcd for C24H39NO2Na: 396.2873;
found: 396.2899.
(9Z,12Z)-N-(4-Hydroxyphenyl)linoleamide (9dm)
HRMS (ESI-TOF): m/z [M + Na]+ calcd for C26H37NO2Na: 418.2717;
found: 418.2767.
Yield: 174 mg (94%); colorless powder; mp 86–87 °C.
IR (KBr): 3319 (NH), 1655 (CON) cm–1
.
1H NMR (400 MHz, DMSO-d6): = 0.85 (t, J = 6.2 Hz, 3 H, CH3(CH2)4),
1.26–1.33 (m, 14 H, CH3(CH2)3, (CH2)4CH2CH2CO), 1.53–1.55 (m, 2 H,
CH2CH2CO), 1.99–2.02 (m, 4 H, 2 × CH2CH2CH), 2.22 (t, J = 7.4 Hz, 2 H,
CH2CO), 2.72–2.75 (m, 2 H, CHCH2CH), 5.24–5.38 (m, 4 H, 4 × CH),
6.66, 7.34 (d, d, J = 8.7, 8.7 Hz, 2 H, 2 H, C6H4), 9.10 (s, 1 H, NHCO), 9.55
(s, 1 H, OH).
13C NMR (100 MHz, DMSO-d6): = 13.8, 21.9, 25.1, 25.2, 26.5, 26.5,
28.5, 28.6, 28.6, 28.9, 30.8, 36.2, 114.9, 120.8, 127.7, 127.7, 129.6,
129.7, 130.9, 153.0, 170.4.
(4Z,7Z,10Z,13Z,16Z,19Z)-N-(4-Hydroxyphenyl)docosahexaenam-
ide (9hm)
Yield: 36 mg (78%); brown oil.
IR (KBr): 3302 (NH), 1657 (CON) cm–1
.
1H NMR (400 MHz, CDCl3): = 0.97 (t, J = 7.5 Hz, 3 H, CH3CH2CH),
2.03–2.09 (m, 2 H, CH3CH2CH), 2.36–2.40 (m, 2 H, CH2CH2CO), 2.49 (t,
J = 7.1 Hz, 2 H, CH2CO), 2.79–2.85 (m, 10 H, 5 × CHCH2CH), 5.32–5.43
(m, 13 H, 12 × CH, NHCO), 6.71, 7.19 (d, d, J = 8.6, 8.2 Hz, 2 H, 2 H,
C6H4), 7.45 (br s, 1 H, OH).
13C NMR (100 MHz, CDCl3): = 14.3, 20.6, 23.4, 25.6, 25.7, 37.1, 115.6,
123.0, 127.0, 127.9, 128.0, 128.1, 128.3, 128.3, 128.4, 128.6, 129.7,
129.8, 132.1, 153.7, 171.6.
HRMS (ESI-TOF): m/z [M + Na]+ calcd for C24H37NO2Na: 394.2717;
found: 394.2704.
(9Z,12Z,15Z)-N-(4-Hydroxyphenyl)linolenamide (9em)
HRMS (ESI-TOF): m/z [M + Na]+ calcd for C28H37NO2Na: 442.2717;
found: 442.2695.
Yield: 152 mg (82%); colorless powder; mp 81–82 °C.
IR (KBr): 3319 (NH), 1655 (CON) cm–1
.
1H NMR (400 MHz, CDCl3): = 0.97 (t, J = 7.5 Hz, 3 H, CH3CH2CH),
1.26–1.32 (m, 8 H, (CH2)4CH2CH2CO), 1.66–1.74 (m, 2 H, CH2CH2CO),
2.02–2.11 (m, 4 H, CH3CH2CH, CH2CH2CH), 2.32 (t, J = 7.6 Hz, 2 H, CH2-
CO), 2.77–2.82 (m, 4 H, 2 × CHCH2CH), 5.32–5.39 (m, 6 H, 6 × CH),
6.73, 7.23 (d, d, J = 8.8, 8.8 Hz, 2 H, 2 H, C6H4), 6.83 (s, 1 H, NHCO), 7.30
(s, 1 H, OH).
13C NMR (100 MHz, CDCl3): = 20.6, 22.6, 22.7, 25.5, 25.6, 25.8, 27.2,
29.2, 29.3, 29.3, 29.3, 29.6, 29.6, 29.8, 31.5, 31.9, 37.4, 116.2, 127.1,
127.7, 127.9, 128.0, 128.3, 128.3, 129.6, 130.1, 130.3, 130.3, 132.0,
153.7, 172.6.
References
(1) Baillie, T. A. Chem. Res. Toxicol. 2006, 19, 889.
(2) (a) Chen, C.; Krausz, K. W.; Idle, J. R.; Gonzalez, F. J. J. Biol. Chem.
2008, 283, 4543. (b) Manyike, P. T.; Kharasch, E. D.; Kalhorn, T.
F.; Slattery, J. T. Clin. Pharmacol. Ther. 2000, 67, 275. (c) Webster,
P. A.; Roberts, D. W.; Benson, R. W.; Kearns, G. L. J. Clin. Pharma-
col. 1996, 36, 397.
(3) Högestätt, E. D.; Jönsson, B. A. G.; Ermund, A.; Andersson, D. A.;
Björk, H.; Alexander, J. P.; Cravatt, B. F.; Basbaum, A. I.; Zygmunt,
P. M. J. Biol. Chem. 2005, 280, 31405.
HRMS (ESI-TOF): m/z [M + Na]+ calcd for C24H35NO2Na: 392.2560;
found: 392.2568.
(4) (a) Deshpande, L. S.; DeLorenzo, R. J. Neuroreport 2011, 22, 15.
(b) Ottani, A.; Leone, S.; Sandrini, M.; Ferrari, A.; Bertolini, A.
Eur. J. Pharmacol. 2006, 531, 280.
(E)-N-(4-Hydroxyphenyl)elaidamide (9fm)
Yield: 181 mg (97%); colorless powder; mp 117–119 °C.
(5) Li, G.; Szostak, M. Nat. Commun. 2018, 9, 4165.
IR (KBr): 3332 (NH), 1655 (CON) cm–1
.
© 2019. Thieme. All rights reserved. — Synthesis 2019, 51, A–N