1518 J ournal of Medicinal Chemistry, 2003, Vol. 46, No. 8
Lo´pez-Rodrı´guez et al.
1
1153, 1078, 916, 712. H NMR (200 MHz, CDCl3, δ): 0.88 (t,
CDCl3, δ): 0.88 (t, 3H, J ) 6.8 Hz, 3H-20), 1.25-1.29 (m, 6H,
2H-17, 2H-18, 2H-19), 1.76-1.89 (m, 2H, 2H-3), 2.02-2.16 (m,
4H, 2H-4, 2H-16), 2.46 (t, 2H, J ) 7.6 Hz, 2H-2), 2.79-2.82
(m, 6H, 2H-7, 2H-10, 2H-13), 4.61 (s, 2H, CH2-N), 4.74 (s,
2H, CH2-N), 5.30-5.46 (m, 8H, vinylic-H), 6.93-6.99 (m, 4H,
2H-3′, 2H-4′), 7.25-7.27 (m, 2H, 2H-5′). 13C NMR (50 MHz,
CDCl3, δ): 14.0, 22.6 (2C), 25.1, 25.6 (3C), 26.6, 27.2, 29.3, 31.5,
32.4, 33.6, 127.5, 127.9 (2C), 128.1 (2C), 128.2, 128.3, 128.4,
128.6, 128.7, 129.3 (2C), 130.5 (2C), 139.8 (2C), 176.1.
3H, J ) 6.8 Hz, 3H-20), 1.19-1.32 (m, 6H, 2H-17, 2H-18, 2H-
19), 1.54-1.77 (m, 3H, 2H-4, 1H-4′), 1.95-2.16 (m, 5H, 1H-4′,
2H-3, 2H-16), 2.32 (t, 2H, J ) 7.8 Hz, 2H-2), 2.50-2.64 (m,
1H, H-3′), 2.78-2.86 (m, 6H, 2H-7, 2H-10, 2H-13), 3.56 (dd,
1H, J ) 8.8, 5.6 Hz, H-C-O), 3.69-4.13 (m, 5H, H-C-O),
5.26-5.41 (m, 8H, vinylic-H). 13C NMR (50 MHz, CDCl3, δ):
14.0, 22.5, 24.7, 25.6 (3C), 26.5, 27.2, 29.0, 29.3, 31.5, 33.6,
38.3, 65.7, 67.7, 70.5, 127.5, 127.8, 128.1, 128.2, 128.6, 128.8,
128.9, 130.5, 173.4.
(()-(F u r -2-yl)eth yl (5Z,8Z,11Z,14Z)-Icosa -5,8,11,14-tet-
r a en oa te, 11. Yield ) 30% for method A. Yield ) 68% for
method B. Rf ) 0.16 (hexane/chloroform, 3:2). IR (CH2Cl2,
cm-1): 3013, 2957, 2930, 2856, 1736, 1456, 1375, 1244, 1153,
1055, 1011. 1H NMR (300 MHz, CDCl3, δ): 0.87 (t, 3H, J )
6.8 Hz, 3H-20), 1.24-1.36 (m, 6H, 2H-17, 2H-18, 2H-19), 1.56
(d, 3H, J ) 6.9 Hz, CH3-CH), 1.68 (quint, 2H, J ) 7.5 Hz,
2H-3), 2.00-2.11 (m, 4H, 2H-4, 2H-16), 2.30 (t, 2H, J ) 7.5
Hz, 2H-2), 2.74-2.83 (m, 6H, 2H-7, 2H-10, 2H-13), 5.28-5.42
(m, 8H, vinylic-H), 5.96 (q, 1H, J ) 6.6 Hz, H-1′′), 6.28-6.32
(m, 2H, H-3′, H-4′), 7.35-7.36 (m, 1H, H-5′). 13C NMR (50 MHz,
CDCl3, δ): 14.0, 18.2, 22.6, 24.8, 25.6 (3C), 26.5, 27.2, 29.3,
31.5, 33.8, 64.8, 107.6, 110.2, 127.5, 127.9, 128.2 (2C), 128.6,
128.8, 128.9, 130.4, 142.4, 153.6, 172.7.
Th ien -3-ylm eth yl (5Z,8Z,11Z,14Z)-Icosa -5,8,11,14-tet-
r a en oa te, 18. Meth od A. Rf ) 0.22 (hexane/ethyl acetate, 25:
1). Yield ) 89%. IR (CHCl3, cm-1): 3016, 2957, 2930, 2856,
1
1730, 1439, 1251, 1157. H NMR (300 MHz, CDCl3, δ): 0.88
(t, 3H, J ) 7.2 Hz, 3H-20), 1.25-1.37 (m, 6H, 2H-17, 2H-18,
2H-19), 1.71 (quint, 2H, J ) 7.5 Hz, 2H-3), 2.01-2.13 (m, 4H,
2H-4, 2H-16), 2.34 (t, 2H, J ) 7.5 Hz, 2H-2), 2.75-2.84 (m,
6H, 2H-7, 2H-10, 2H-13), 5.11 (s, 2H, 2H-1′′), 5.30-5.41 (m,
8H, vinylic-H), 7.07 (dd, 1H, J ) 4.8, 1.2 Hz, H-4′), 7.28-7.31
(m, 2H, H-2,′ H-5′). 13C NMR (50 MHz, CDCl3, δ): 14.0, 22.6,
24.7, 25.6 (3C), 26.5, 27.2, 29.3, 31.5, 33.6, 61.0, 124.2, 126.2,
127.5, 127.6, 127.9, 128.1, 128.2, 128.6, 128.9 (2C), 130.5,
136.9, 173.3.
(5Z,8Z,11Z,14Z)-N-(Th ien -3-ylm et h yl)icosa -5,8,11,14-
tetr a en a m id e, 19. Meth od B. Yield ) 40%. Rf ) 0.48
(chloroform/diethyl ether, 9:1). IR (CHCl3, cm-1): 3352, 3018,
2930, 2858, 1718, 1655, 1522, 1458, 1420, 1049, 908. 1H NMR
(200 MHz, CDCl3, δ): 0.88 (t, 3H, J ) 6.6 Hz, 3H-20), 1.25-
1.39 (m, 6H, 2H-17, 2H-18, 2H-19), 1.74 (quint, 2H, J ) 7.1
Hz, 2H-3), 2.00-2.24 (m, 6H, 2H-4, 2H-16, 2H-2), 2.76-2.86
(m, 6H, 2H-7, 2H-10, 2H-13), 4.44 (d, 2H, J ) 5.6 Hz, 2H-1′′),
5.26-5.46 (m, 8H, vinylic-H), 5.68 (br s, 1H, NH), 7.02 (dd,
1H, J ) 4.9, 1.2 Hz, H-4′), 7.12-7.15 (m, 1H, H-2′), 7.29 (dd,
1H, J ) 4.9, 2.9 Hz, H-5′). 13C NMR (50 MHz, CDCl3, δ): 14.0,
22.5, 25.5, 25.6 (3C), 26.7, 27.2, 29.3, 31.5, 36.0, 38.7, 122.3,
126.4, 127.3, 127.5, 127.8, 128.1, 128.2, 128.6, 128.8, 129.1,
130.5, 139.1, 172.5.
Data of (+)-12 and (-)-13 were identical to those recorded
for the racemic material (11) except for the optical rotation.
(+)-12: [R]20D +29.6 (c 3.0, ethanol). (-)-13: [R]20D -31.7 (c 2.9,
ethanol).
(()-(5Z,8Z,11Z,14Z)-N-[1-(F u r -2-yl)et h yl]icosa -5,8,11,-
14-tetr a en a m id e, 14. Meth od B. Rf ) 0.22 (chloroform).
Yield ) 72%. IR (CDCl3, cm-1): 3327, 3013, 2959, 2930, 2856,
1662, 1506, 1452, 1375, 1227, 1151, 1096, 1072, 1013. 1H NMR
(300 MHz, CDCl3, δ): 0.90 (t, 3H, J ) 6.8 Hz, 3H-20), 1.24-
1.39 (m, 6H, 2H-17, 2H-18, 2H-19), 1.48 (d, 3H, J ) 6.9 Hz,
CH-CH3), 1.68-1.79 (m, 2H, 2H-3), 2.03-2.22 (m, 6H, 2H-4,
2H-16, 2H-2), 2.78-2.86 (m, 6H, 2H-7, 2H-10, 2H-13), 5.23 (q,
1H, J ) 7.3 Hz, CH-CH3), 5.32-5.42 (m, 8H, vinylic-H), 5.68
(br d, 1H, J ) 7.8 Hz, NH), 6.18 (dt, 1H, J ) 3.3, 0.8 Hz, H-3′),
6.32 (dd, 1H, J ) 3.3, 1.9 Hz, H-4′), 7.35 (dd, 1H, J ) 1.8, 0.7
Hz, H-5′). 13C NMR (75 MHz, CDCl3, δ): 13.9, 19.5, 22.4, 25.2,
25.4 (2C), 25.5, 26.4, 27.0, 29.1, 31.3, 35.9, 42.6, 105.4, 110.0,
127.3, 127.7, 128.0 (2C), 128.4, 128.6, 128.9, 130.3, 141.7,
155.2, 171.6.
(5Z,8Z,11Z,14Z)-N-[(1-Meth yl-1H-p yr r ol-2-yl)m eth yl]i-
cosa -5,8,11,14-tetr a en a m id e, 20. Meth od A. Rf ) 0.34
(hexane/ethyl acetate, 3:2). Yield ) 48%. IR (CHCl3, cm-1):
1
3018, 2926, 2854, 1655, 1508, 1425, 930. H NMR (200 MHz,
CDCl3, δ): 0.88 (t, 3H, J ) 6.0 Hz, 3H-20), 1.25-1.39 (m, 6H,
2H-17, 2H-18, 2H-19), 1.72 (quint, 2H, J ) 7.3 Hz, 2H-3),
2.00-2.24 (m, 6H, 2H-4, 2H-16, 2H-2), 2.79-2.86 (m, 6H, 2H-
7, 2H-10, 2H-13), 3.57 (s, 3H, N-CH3), 4.43 (d, 2H, J ) 5.1
Hz, 2H-1′′), 5.30-5.41 (m, 8H, vinylic-H), 5.43 (br s, 1H, NH),
6.06 (d, 2H, J ) 2.4 Hz, H-3′, H-4′), 6.61 (t, 1H, J ) 2.2 Hz,
H-5′). 13C NMR (50 MHz, CDCl3, δ): 14.0, 22.5, 25.5, 25.6 (3C),
26.7, 27.2, 29.3, 31.5, 33.7, 35.1, 36.0, 107.0, 108.7, 123.1, 127,5,
127.8, 128.1, 128.2, 128.6 (2C), 128.8, 129.0, 130.5, 172.0.
(5Z,8Z,11Z,14Z)-N-[2-(F u r -2-yl)eth yl]icosa -5,8,11,14-tet-
r a en a m id e, 21. Meth od B. Rf ) 0.60 (methylene chloride/
ethyl acetate, 9:1). Yield ) 29%. IR (CH2Cl2, cm-1): 3350, 2924,
2854, 2361, 2343, 1641, 1545, 1439, 1377, 1068, 1026. 1H NMR
(200 MHz, CDCl3, δ): 0.82 (t, 3H, J ) 6.7 Hz, 3H-20), 1.18-
1.36 (m, 6H, 2H-17, 2H-18, 2H-19), 1.62 (quint, 2H, J ) 7.3
Hz, 2H-3), 1.93-2.12 (m, 6H, 2H-4, 2H-16, 2H-2), 2.71-2.80
(m, 8H, 2H-7, 2H-10, 2H-13, NH-CH2-CH2), 3.47 (q, 2H, J
) 6.3 Hz, NH-CH2), 5.20-5.37 (m, 8H, vinylic-H), 5.54 (br s,
1H, NH), 6.00 (dd, 1H, J ) 3.0, 0.7 Hz, H-3′), 6.24 (dd, 1H, J
) 3.0, 1.9 Hz, H-4′), 7.27 (dd, 1H, J ) 1.5, 0.7 Hz, H-5′). 13C
NMR (50 MHz, CDCl3, δ): 14.1, 22.6, 25.5, 25.6 (3C), 26.6,
27.2, 28.2, 29.3, 31.5, 36.1, 38.0, 106.4, 110.3, 127.5, 127.8,
128.1, 128.2, 128.6, 128.7, 129.1, 130.5, 141.6, 153.0, 174.0.
Th ien -2-ylm eth yl (5Z,8Z,11Z,14Z)-Icosa -5,8,11,14-tet-
r a en oa te, 15. Meth od A. Rf ) 0.66 (chloroform). Yield ) 49%.
IR (CHCl3, cm-1): 3013, 2926, 2858, 2856, 1736, 1439, 1230,
1
1146, 702. H NMR (300 MHz, CDCl3, δ): 0.88 (t, 3H, J ) 6.9
Hz, 3H-20), 1.25-1.37 (m, 6H, 2H-17, 2H-18, 2H-19), 1.70
(quint, 2H, J ) 7.5 Hz, 2H-3), 2.01-2.13 (m, 4H, 2H-4, 2H-
16), 2.33 (t, 2H, J ) 7.8 Hz, 2H-2), 2.75-2.84 (m, 6H, 2H-7,
2H-10, 2H-13), 5.26 (s, 2H, 2H-1′′), 5.28-5.42 (m, 8H, vinylic-
H), 6.97 (dd, 1H, J ) 5.1, 3.6 Hz, H-4′), 7.08 (d, 1H, J ) 3.3
Hz, H-3′), 7.30 (d, 1H, J ) 5.4 Hz, H-5′). 13C NMR (50 MHz,
CDCl3, δ): 14.0, 22.6, 24.7, 25.6 (3C), 26.5, 27.2, 29.3, 31.5, 33.6,
60.4, 126.7, 126.8, 127.5, 127.9, 128.0, 128.1, 128.2, 128.6,
128.8, 128.9, 130.5, 138.1, 173.2.
(5Z,8Z,11Z,14Z)-N-(Th ien -2-ylm et h yl)icosa -5,8,11,14-
tetr a en a m id e, 16. Meth od A. Rf ) 0.39 (methylene chloride/
diethyl ether, 95:5). Yield ) 72%. IR (CH2Cl2, cm-1): 3319,
2930, 2858, 1713, 1651, 1545, 1529, 1458, 1431, 1367, 1223,
1
1159, 1043, 852, 702. H NMR (300 MHz, CDCl3, δ): 0.92 (t,
3H, J ) 6.6 Hz, 3H-20), 1.22-1.33 (m, 6H, 2H-17, 2H-18, 2H-
19), 1.75 (quint, 2H, J ) 7.4 Hz, 2H-3), 2.05-2.17 (m, 4H, 2H-
4, 2H-16), 2.22 (t, 2H, J ) 7.5 Hz, 2H-2), 2.82-2.85 (m, 6H,
2H-7, 2H-10, 2H-13), 4.61 (d, 2H, J ) 5.4 Hz, 2H-1′′), 5.32-
5.39 (m, 8H, vinylic-H), 6.08 (br s, 1H, NH), 6.96 (m, 2H, H-3′,
H-4′), 7.22-7.24 (m, 1H, H-5′). 13C NMR (50 MHz, CDCl3, δ):
14.0, 22.6, 25.4, 25.6 (3C), 26.6, 27.2, 29.3, 31.5, 35.9, 38.3,
125.2, 126.0, 126.9 (2C), 127.5, 127.8, 128.1, 128.2, 128.6,
129.0, 130.5, 141.0, 176.0.
(5Z,8Z,11Z,14Z)-N-[2-(F u r -3-yl)eth yl]icosa -5,8,11,14-tet-
r a en a m id e, 22. Meth od B. Rf ) 0.38 (chloroform/diethyl
ether, 9:1). Yield ) 42%. IR (CH2Cl2, cm-1): 3296, 3011, 2955,
2928, 2856, 1643, 1553, 1502, 1454, 1439, 1161, 1066, 1026,
1
874. H NMR (200 MHz, CDCl3, δ): 0.89 (t, 3H, J ) 6.8 Hz,
3H-20), 1.25-1.39 (m, 6H, 2H-17, 2H-18, 2H-19), 1.62 (m, 2H,
2H-3), 2.00-2.18 (m, 6H, 2H-4, 2H-16, 2H-2), 2.63 (t, 2H, J )
6.8 Hz, NH-CH2-CH2), 2.78-2.86 (m, 6H, 2H-7, 2H-10, 2H-
13), 3.46 (q, 2H, J ) 6.8 Hz, NH-CH2), 5.33-5.41 (m, 9H,
vinylic-H, NH), 6.28-6.29 (m, 1H, H-4′), 7.26-7.27 (m, 1H,
H-2′), 7.38 (t, 1H, J ) 1.7 Hz, H-5′). 13C NMR (50 MHz, CDCl3,
(5Z,8Z,11Z,14Z)-N,N-Bis(th ien -2-ylm eth yl)icosa -5,8,11,-
14-tetr a en a m id e, 17. Meth od A. Rf ) 0.21 (chloroform/
hexane, 4:1). Yield ) 27%. IR (CH2Cl2, cm-1): 3055, 2961,
2930, 2856, 1713, 1636, 1420, 1364, 1094. 1H NMR (200 MHz,