ACS Chemical Neuroscience
Research Article
General Procedure for the Synthesis of Compounds 8a−8t. To a
solution of compound 7 (15 mg, 0.03 mmol) in t-BuOH/H2O mixture
(2:1, 2 mL), sodium ascorbate (1.2 mg, 0.006 mmol) and CuSO4 (1.2
mg, 0.0045 mmol) were added at room temperature. To this mixture,
aryl or aliphatic azide (0.06 mmol) was added and the reaction mixture
was sonicated at 45 °C until its completion monitored by TLC. The
crude mixture was extracted with ethyl acetate (3 × 50 mL), and the
combined organic layer was dried over sodium sulfate. Solvent was
removed under reduced pressure, and the product was purified
through column chromatography (eluent: ethyl acetate/hexane;
15:85) to result in pure 8a−8t in 72−82% yields.
1H), 7.52 (s, 1H), 7.42−7.25 (m, 2H), 7.01 (m, 1H), 6.28 (d, 2H, J =
16 Hz), 6.14 (d, J = 12 Hz), 5.81 (s, 1H), 5.34 (s, 2H), 2.37 (s, 3H),
2.33 (s, 3H), 2.32(s, 3H), 2.00 (s, 3H), 1.71 (s, 3H), 1.71−1.26 (m,
6H), 1.03 (s, 6H). 13C NMR (101 MHz, CDCl3) δ 167.0, 154.2,
140.2, 138.5, 137.9, 137.8, 137.4, 135.1, 131.6, 130.8, 130.3, 129.6,
129.1, 122.0, 118.1, 117.8, 57.1, 39.8, 34.4, 33.3, 29.2, 21.9, 20.0, 19.6,
19.4, 14.2, 13.1. HRMS [M + H]+ 486.3118.
(2E,4E,6E,8E)-(1-(Naphthalen-1-yl)-1H-1,2,3-triazol-4-yl)methyl
3,7-Dimethyl-9-(2,6,6-trimethylcyclohex-1-en-1-yl)nona-2,4,6,8-tet-
raenoate (8h). 1H NMR (400 MHz, CDCl3) δ 8.02 (m, 2H), 7.96 (s,
1H), 7.63−7.58 (m, 5H), 7.02 (m, 1H), 6.29 (d, 2H, J = 16 Hz), 6.12
(d, 2H, J = 16 Hz), 5.85 (s, 1H), 5.44 (s, 2H), 2.38 (s, 3H), 2.03 (s,
3H), 1.71 (s, 3H), 1.61−1.26 (m, 6H), 1.03 (s, 6H). 13C NMR (101
MHz, CDCl3) δ 167.0, 154.2, 143.6, 140.2, 137.8, 137.3, 135.0, 134.3,
133.7, 131,7, 130.6, 130.3, 129.5, 129.1, 128.6, 128.4, 128.1, 127.2,
126.4, 125.1, 123.7, 122.5, 117.8, 57.2, 39.8, 34.4, 33.3, 29.1, 21.9, 19.4,
14.2, 13.1. HRMS [M]+ 507.2885.
(2E,4E,6E,8E)-(1-(m-Tolyl)-1H-1,2,3-triazol-4-yl)methyl 3,7-Di-
methyl-9-(2,6,6-trimethylcyclohex-1-en-1-yl)nona-2,4,6,8-tetrae-
noate (8i). 1H NMR (100 MHz, CDCl3) δ 8.01 (s, 1H), 7.72 (s, 1H),
7.71−7.59 (m, 3H), 6.73 (t, 1H, J = 16 Hz), 6.21 (m, 2H), 5.76 (m,
2H), 5.31 (s, 2H), 5.03 (s 1H), 2.21 (s, 3H), 2.01−1.89 (m, 4H), 1.73
(s, 3H), 1.60 (m, 2H), 1.41 (s, 3H), 1.19 (s, 6H). 13C NMR (101
MHz, CDCl3) δ 171.7, 153.1, 142.8, 133.2, 130.8, 129.7, 129.5, 128.0,
126.6, 125.5, 124.8, 117.3, 115.4, 57.0, 40.9, 35.0, 32.0, 29.8, 26.0, 22.7,
14.1, 13.0. HRMS [M]+ 471.2883.
(2E,4E,6E,8E)-(1-(2-Nitrophenyl)-1H-1,2,3-triazol-4-yl)methyl 3,7-
Dimethyl-9-(2,6,6-trimethylcyclohex-1-en-1-yl)nona-2,4,6,8-tetrae-
1
noate (8a). H NMR (100 MHz, CDCl3) δ 8.61 (m, 1H), 8.32 (m,
1H), 8.19 (m, 2H), 7.76 (m, 2H), 7.60 (s, 1H), 6.89 (t, 1H, J = 16
Hz), 6.23 (m, 2H), 5.81 (s, 1H), 5.17 (s, 2H), 2.36 (s, 3H), 2.06 (s,
3H), 2.04−2.19 (m, 4H), 1.72 (s, 3H), 1.43 (m, 2H), 1.10 (s, 6H). 13C
NMR (101 MHz, CDCl3) δ 166.9, 154.5, 143.5, 137.8, 135.1, 131.4,
131.1, 130.5, 126.1, 125.8, 125.0, 123.4, 122.1, 122.0, 118.5, 117.6,
117.4, 56.9, 34.5, 30.8, 29.8, 25.9, 20.4, 13.9, 13.2. HRMS [M]+
502.2578.
(2E,4E,6E,8E)-(1-(3-Nitrophenyl)-1H-1,2,3-triazol-4-yl)methyl 3,7-
Dimethyl-9-(2,6,6-trimethylcyclohex-1-en-1-yl)nona-2,4,6,8-tetrae-
noate (8b). 1H NMR (100 MHz, CDCl3) δ 8.08 (s, 1H), 7.92 (s, 1H),
7.77−7.61 (m, 3H), 6.85 (t, 1H, J = 16 Hz), 6.23 (m, 2H), 5.79 (m,
2H), 5.34 (s, 2H), 5.14 (s 1H), 2.32 (s, 3H), 2.02−1.93 (m, 4H), 1.75
(s, 3H), 1.62 (m, 2H), 1.42 (s, 3H), 1.23 (s, 6H). 13C NMR (101
MHz, CDCl3) δ 173.8, 154.2, 143.3, 134.0, 131.3, 130.9, 130.3, 128.2,
126.8, 125.8, 125.4, 118.5, 118.0, 56.8, 41.2, 34.9, 31.8, 29.9, 26.2, 22.9,
14.2, 12.9. HRMS [M]+ 502.2579.
(2E,4E,6E,8E)-(1-(4-Nitrophenyl)-1H-1,2,3-triazol-4-yl)methyl 3,7-
Dimethyl-9-(2,6,6-trimethylcyclohex-1-en-1-yl)nona-2,4,6,8-tetrae-
noate (8c). 1H NMR (400 MHz, CDCl3) δ 8.57 (s, 1H), 8.43 (s, 1H),
7.97−7.97 (m, 2H), 7.81 (m, 1H), 7.43 (dd, J = 16, 12 Hz), 6.80 (d,
2H, J = 16 Hz), 6.58 (d, 2H, J = 16 Hz), 6.85 (s, 1H), 5.89 (s, 2H),
2.60 (s, 3H), 2.52 (s, 3H), 1.98−1.80 (m, 6H), 1.82 (s, 3H), 1.24 (s,
6H). 13C NMR (101 MHz, CDCl3) δ 169.3, 157.5, 148.8, 139.7, 139.1,
136.90, 132.5, 131.9, 132.5, 129.8, 129.7, 129.0, 123.4, 131.3, 118.7,
116.8, 57.9, 39.4, 34.7, 33.5, 29.3, 21.5, 18.9, 14.3, 13.4. HRMS [M]+
502.2578.
(2E,4E,6E,8E)-(1-Benzyl-1H-1,2,3-triazol-4-yl)methyl 3,7-Dimeth-
yl-9-(2,6,6-trimethylcyclohex-1-en-1-yl)nona-2,4,6,8-tetraenoate
1
(8j). H NMR (400 MHz, CDCl3) δ 7.57 (m, 6H), 6.98 (m, 1H),
6.31−6.09 (m, 4H), 5.75 (s, 1H), 5.62 (s, 2H), 4.31 (s, 2H), 2.32 (s,
3H), 2.03 (s, 3H), 1.79 (s, 3H), 1.68−1.44 (m, 6H), 1.00 (s, 6H). 13C
NMR (101 MHz, CDCl3) δ 167.0, 153.9, 143.4, 140.0, 137.8, 137.4,
135.0, 131.5, 130.2, 129.6, 129.0, 123.6, 117.9, 63.2, 57.2, 50.6, 39.8,
31.8, 30.4, 29.5, 29.4, 29.2, 29.1, 26.6, 25.9, 22.7, 14.2, 13.1. HRMS
[M]+ 471.2884.
(2E,4E,6E,8E)-(1-(2-(Trifluoromethyl)phenyl)-1H-1,2,3-triazol-4-
yl)methyl 3,7-Dimethyl-9-(2,6,6-trimethylcyclohex-1-en-1-yl)nona-
1
2,4,6,8-tetraenoate (8k). H NMR (400 MHz, CDCl3) δ 7.92−7.57
(m, 5H), 7.01 (m, 1H), 6.31−6.13 (m, 5H), 5.37 (s, 2H), 2.36 (s, 3H),
1
2.02−1.62 (m, 4H), 1.60−1.23 (m, 8H), 1.45 (s, 6H). H NMR (101
(2E,4E,6E,8E)-(1-(4-Bromophenyl)-1H-1,2,3-triazol-4-yl)methyl
MHz, CDCl3) δ 166.7, 153.8, 143.6, 138.5, 137.4, 136.9, 135.8, 133.1,
130.4, 129.2, 127.4, 126.4, 123.8, 121.4, 118.3, 112.7, 56.9, 40.2, 34.0,
29.1, 26.1, 21.9, 19.4, 14.2, 14.1. HRMS [M]+ 525.2601.
3,7-Dimethyl-9-(2,6,6-trimethylcyclohex-1-en-1-yl)nona-2,4,6,8-tet-
1
raenoate (8d). H NMR (400 MHz, CDCl3) δ 8.08 (s, 1H), 7.60−
7.51 (m, 4H), 6.74 (m, 1H), 6.59−6.50 (m, 3H), 6.39 (m, 1H), 5.94
(s, 1H), 5.33 (s, 2H), 2.15 (m, 2H), 2.07 (s, 3H), 1.81 (s, 3H), 1.80 (s,
3H), 1.56 (m, 2H), 1.59 (m, 2H), 0.99 (s, 6H). 13C NMR (101 MHz,
CDCl3) δ 168.4, 152.4, 148.1, 137. 3, 136.9, 135.4, 132.1, 132.1, 131.5,
130.8, 129.2, 121.8, 121.8, 120.5, 119.6, 118.8, 51.7, 38.5, 34.8, 33.8,
28.8, 28.8, 21.0, 20.3, 15.9, 15.9. HRMS [M]+ 535.1830.
(2E,4E,6E,8E)-(1-(4-Chlorophenyl)-1H-1,2,3-triazol-4-yl)methyl
3,7-Dimethyl-9-(2,6,6-trimethylcyclohex-1-en-1-yl)nona-2,4,6,8-tet-
1
raenoate (8l). H NMR (400 MHz, CDCl3) δ 8.27 (s, 1H), 7.91 (m,
2H), 7.72 (m, 2H), 7.24 (t, 1H, J = 16, 12 Hz), 6.50 (m, 2H), 6.35 (m,
2H), 6.02 (s, 1H), 5.56 (s, 2H), 2.59 (s, 3H), 2.22 (s, 3H), 1.93 (s,
3H), 1.90−1.69 (m, 6H), 1.24 (s, 6H). 13C NMR (101 MHz, CDCl3)
δ 167.0, 154.3, 140.3, 137.8, 137.3, 135.6, 134.9, 134.8, 131.8, 130.3,
130.1, 129.5, 129.1, 121.9, 117.6, 57.0, 39.8, 34.4, 33.3, 29.1, 21.9, 19.4,
14.2, 13.1. HRMS [M]+ 491.2339.
(2E,4E,6E,8E)-(1-(2-Fluorophenyl)-1H-1,2,3-triazol-4-yl)methyl
3,7-Dimethyl-9-(2,6,6-trimethylcyclohex-1-en-1-yl)deca-2,4,6,8-tet-
raenoate (8e). 1H NMR (400 MHz, CDCl3) δ 8.08 (s, 1H), 7.87 (m,
1H), 7.36−7.19 (m, 3H), 6.93 (dd, 1H, J = 16, 12 Hz), 6.20 (d, 2H, J
= 16 Hz), 6.05 (d, 2H, J = 16 Hz), 5.73 (s, 1H), 5.29 (s, 2H), 2.29 (s,
3H), 1.92 (s, 3H), 1.63−1.39 (m, 6H), 1.18 (s, 9H). 13C NMR (101
MHz, CDCl3) δ 167.0, 154.2, 140.1, 137.8, 137.4, 135.0, 131.6, 130.5,
130.4, 130.3, 129.6, 129.1, 125.4, 125.4, 125.1, 117.7, 117.3, 117.1,
56.9, 39.8, 34.3, 33.2, 32.0, 29.7, 29.0, 22.9, 21.7, 19.4, 14.2, 13.0.
HRMS [M]+ 475.2631.
(2E,4E,6E,8E)-(1-(2,4,6-Trichlorophenyl)-1H-1,2,3-triazol-4-yl)-
methyl 3,7-Dimethyl-9-(2,6,6-trimethylcyclohex-1-en-1-yl)nona-
1
2,4,6,8-tetraenoate (8m). H NMR (400 MHz, CDCl3) δ 8.20 (s,
1H), 7.71 (s, 1H), 7.66 (s, 1H), 7.24 (m, 1H), 6.50 (d, 2H, J = 16 Hz),
6.35 (d, 2H, J = 12 Hz), 6.03 (s, 1H), 5.57 (s, 2H), 2.59 (s, 3H), 2.22
(s, 3H), 1.92, (s, 3H), 1.83−1.69 (m, 6H), 1.24 (s, 6H). 13C NMR
(101 MHz, CDCl3) δ 167.3, 154.5, 140.3, 137.4, 137.5, 137.6, 135.3,
132.0, 130.6, 130.2, 129.5, 129.1, 129.0, 120.8, 117.7, 57.1, 39.7, 34.3,
33.2, 29.1, 21.9, 19.4, 14.0, 13.3. HRMS [M]+ 457.2726.
(2E,4E,6E,8E)-(1-(2,4-Difluorophenyl)-1H-1,2,3-triazol-4-yl)methyl
3,7-Dimethyl-9-(2,6,6-trimethylcyclohex-1-en-1-yl)nona-2,4,6,8-tet-
1
raenoate (8f). H NMR (400 MHz, CDCl3) δ 8.82 (s, 1H), 7.85 (s,
(2E,4E,6E,8E)-(1-(2-Bromophenyl)-1H-1,2,3-triazol-4-yl)methyl
1H), 7.963−7.38 (m, 2H), 7.13 (m, 1H), 6.37 (d, 2H, J = 16 Hz), 6.19
(d, J = 12 Hz), 5.92 (s, 1H), 5.44 (s, 2H), 2.43 (s, 3H), 2.12 (s, 3H),
1.83 (s, 3H), 1.74−1.25 (m, 6H), 1.03 (s, 6H).13C NMR (101 MHz,
CDCl3) δ 168.2, 155.3, 141.1, 139.4, 138.0, 137.8, 137.6, 135.5, 131.9,
131.0, 130.8, 129.9, 129.0, 122.8, 117.9, 117.6, 57.5, 34.0, 29.5, 22.0,
19.9, 19.5, 19.3, 14.5, 13.4. HRMS [M + H]+ 493.2539.
3,7-Dimethyl-9-(2,6,6-trimethylcyclohex-1-en-1-yl)nona-2,4,6,8-tet-
1
raenoate (8n). H NMR (400 MHz, CDCl3) δ 8.13 (s, 1H), 7.72 (s,
1H), 7.57 (d, 2H, m), 7.63 (m, 1H), 7.22 (m, 1H), 6.52 (d, 2H, J = 16
Hz), 6.33 (d, 2H, J = 12 Hz), 6.08 (s, 1H), 5.59 (s, 2H), 2.60 (s, 3H),
2.24 (s, 3H), 1.93, (s, 3H), 1.85−1.70 (m, 6H), 1.23 (s, 6H). 13C
NMR (101 MHz, CDCl3) δ 167.5, 154.3, 140.4, 137.9, 137.7, 137.6,
134.8, 132.0, 131.0, 130.2, 129.8, 129.0, 129.0, 121.1, 117.9, 56.9, 38.2,
34.5, 33.4, 29.0, 22.0, 19.5, 14.4, 13.4. HRMS [M]+ 535.1828.
(2E,4E,6E,8E)-(1-(3,4-Dimethylphenyl)-1H-1,2,3-triazol-4-yl)-
methyl 3,7-Dimethyl-9-(2,6,6-trimethylcyclohex-1-en-1-yl)nona-
1
2,4,6,8-tetraenoate (8g). H NMR (400 MHz, CDCl3) δ 8.01 (s,
87
ACS Chem. Neurosci. 2016, 7, 82−89