A. Halldorsson et al. / Tetrahedron 59 (2003) 9101–9109
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4.1.6. 2-Eicosapentaenoyl-1,3-dioctanoylglycerol (2a). To
solution of 1,3-dioctanoylglycerol 1a (350 mg,
2.88–2.75 (m, 8H, vCCH2Cv), 2.33 (t, J¼7.4 Hz, 2H,
CH2COO in EPA), 2.30 (t, J¼7.6 Hz, 4H, CH2COO), 2.15–
2.00 (m, 4H, vCHCH2CH2 and CH3CH2CHv), 1.75–1.63
(m, 2H, CH2CH2COO in EPA), 1.66–1.53 (m, 4H,
CH2CH2COO in dodecanoic acid), 1.40–1.16 (m, 32H,
CH2), 0.96 (t, J¼7.5 Hz, 3H, CH3 in EPA) and 0.87 (t,
J¼6.8 Hz, 6H, CH3) ppm. 13C NMR d 173.2 (2, aCvO),
172.6 (1, bCvO, EPA), 132.0 (1), 128.9 (1), 128.7 (1),
128.5 (1), 128.2 (1), 128.1 (2), 128.0 (1), 127.8 (1), 126.9
(1), 68.9 (1), 62.0 (2), 34.0 (2), 33.5 (1), 31.9 (2), 29.6 (4),
29.4 (2), 29.3 (2), 29.2 (2), 29.1 (2), 26.4 (1), 25.6 (3), 25.5
(1), 24.8 (2), 24.7 (1), 22.6 (2), 20.5 (1), 14.2 (1) and 14.0
(2) ppm. IR nmax 3013 (s, C–H), 2923 (vs, C–H), 2854 (vs,
C–H), 1743 (vs, CvO) cm21. HRMS (API): calcd for
C47H80O6þNH4 m/z 758.6299; found 758.6311 amu.
a
1.02 mmol) and EPA as a free acid (307 mg, 1.02 mmol)
in dichloromethane (2.0 mL) was added DMAP (49 mg,
0.40 mmol) and EDCI (234 mg, 1.22 mmol). The resulting
solution was stirred on a magnetic stirrer hot-plate at rt for
15 h. The reaction was disconnected by passing the reaction
mixture in ether/dichloromethane (10:90) through a short
column packed with silica gel. Solvent removal in vacuo
afforded the pure product as a yellowish oil (576 mg, 90%
1
yield). H NMR d 5.41–5.33 (m, 10H, vCH), 5.33–5.24
(m, 1H, CH2CHCH2), 4.29 (dd, J¼11.9, 4.3 Hz, 2H,
CH2CHCH2), 4.13 (dd, J¼11.9, 5.9 Hz, 2H, CH2CHCH2),
2.86–2.77 (m, 8H, vCCH2Cv), 2.33 (t, J¼7.3 Hz, 2H,
CH2COO in EPA), 2.30 (t, J¼7.6 Hz, 4H, CH2COO), 2.15–
2.02 (m, 4H, vCHCH2CH2 and CH3CH2CHv), 1.75–1.63
(m, 2H, CH2CH2COO in EPA), 1.66–1.54 (m, 4H,
CH2CH2COO in octanoic acid), 1.40–1.16 (m, 16H,
CH2), 0.97 (t, J¼7.5 Hz, 3H, CH3 in EPA) and 0.87 (t,
J¼6.8 Hz, 6H, CH3) ppm. 13C NMR d 173.2 (2, aCvO),
172.6 (1, bCvO, EPA), 132.0 (1), 128.9 (1), 128.7 (1),
128.5 (1), 128.2 (1), 128.1 (2), 128.0 (1), 127.8 (1), 127.0
(1), 68.9 (1), 62.0 (2), 34.0 (2), 33.5 (1), 31.6 (2), 29.0 (2),
28.9 (2), 26.4 (1), 25.6 (3), 25.5 (1), 24.8 (2), 24.7 (1), 22.6
(2), 20.5(1), 14.2(1) and14.0(2) ppm. IRnmax 3013(s, C–H),
4.1.9. 2-Eicosapentaenoyl-1,3-ditetradecanoylglycerol
(2d). The procedure was identical to that for preparing 2a
using 1,3-ditetradecanoylglycerol 1d (350 mg, 0.683 mmol),
EPA (206 mg, 0.683 mmol), DMAP (33 mg, 0.27 mmol)
and EDCI (156 mg, 0.82 mmol) in dichloromethane
(2.0 mL). The product was afforded as a yellowish oil
(501 mg, 92% yield). 1H NMR d 5.41–5.33 (m, 10H,
vCH), 5.33–5.24 (m, 1H, CH2CHCH2), 4.29 (dd, J¼11.9,
4.3 Hz, 2H, CH2CHCH2), 4.14 (dd, J¼11.9, 5.9 Hz, 2H,
CH2CHCH2), 2.88–2.75 (m, 8H, vCCH2Cv), 2.33 (t,
J¼7.4 Hz, 2H, CH2COO in EPA), 2.30 (t, J¼7.6 Hz, 4H,
CH2COO), 2.15–2.00 (m, 4H, vCHCH2CH2 and CH3-
CH2CHv), 1.75–1.63 (m, 2H, CH2CH2COO in EPA),
1.66–1.53 (m, 4H, CH2CH2COO in tetradecanoic acid),
1.40–1.16 (m, 40H, CH2), 0.97 (t, J¼7.5 Hz, 3H, CH3 in
EPA) and 0.87 (t, J¼6.8 Hz, 6H, CH3) ppm. 13C NMR d
173.3 (2, aCvO), 172.6 (1, bCvO, EPA), 132.0 (1), 128.9
(1), 128.7 (1), 128.5 (1), 128.2 (2), 128.1 (1), 128.0 (1),
127.8 (1), 127.0 (1), 68.9 (1), 62.0 (2), 34.0 (2), 33.5 (1),
31.9 (2), 29.7 (2), 29.6 (6), 29.5 (2), 29.4 (2), 29.3 (2), 29.1
(2), 26.4 (1), 25.6 (3), 25.5 (1), 24.8 (2), 24.7 (1), 22.7 (2),
20.5 (1), 14.3 (1) and 14.1 (2) ppm. IR nmax 3013 (s, C–H),
2927 (vs, C–H), 2856 (vs, C–H), 1740 (vs, CvO) cm21
.
HRMS (API): calcd for C39H64O6þNH4 m/z 646.5047;
found 646.5037 amu.
4.1.7. 2-Eicosapentaenoyl-1,3-didecanoylglycerol (2b).
The procedure was identical to that for preparing 2a using
1,3-didecanoylglycerol 1b (350 mg, 0.874 mmol), EPA
(264 mg, 0.874 mmol), DMAP (43 mg, 0.35 mmol) and
EDCI (201 mg, 1.05 mmol) in dichloromethane (2.0 mL).
The product was afforded as a yellowish oil (556 mg, 93%
1
yield). H NMR d 5.41–5.33 (m, 10H, vCH), 5.33–5.24
(m, 1H, –CH2CHCH2), 4.29 (dd, J¼11.9, 4.3 Hz, 2H,
CH2CHCH2), 4.13 (dd, J¼11.9, 5.9 Hz, 2H, CH2CHCH2),
2.88–2.75 (m, 8H, vCCH2Cv), 2.33 (t, J¼7.3 Hz, 2H,
CH2COO in EPA), 2.30 (t, J¼7.6 Hz, 4H, CH2COO), 2.15–
2.00 (m, 4H, vCHCH2CH2 and CH3CH2CHv), 1.75–1.63
(m, 2H, CH2CH2COO in EPA), 1.66–1.53 (m, 4H,
CH2CH2COO in decanoic acid), 1.40–1.17 (m, 24H,
CH2), 0.96 (t, J¼7.5 Hz, 3H, CH3 in EPA) and 0.87 (t,
J¼6.8 Hz, 6H, CH3) ppm. 13C NMR d 173.2 (2, aCvO),
172.6 (1, bCvO, EPA), 132.0 (1), 128.9 (1), 128.7 (1),
128.5 (1), 128.2 (1), 128.1 (2), 128.0 (1), 127.8 (1), 126.9
(1), 68.9 (1), 62.0 (2), 34.0 (2), 33.5 (1), 31.8 (2), 29.4 (2),
29.2 (4), 29.0 (2), 26.4 (1), 25.6 (3), 25.5 (1), 24.8 (2), 24.7
(1), 22.6 (2), 20.5 (1), 14.2 (1) and 14.0 (2) ppm. IR nmax
3013 (s, C–H), 2924 (vs, C–H), 2854 (vs, C–H), 1740 (vs,
CvO) cm21. HRMS (API): calcd for C43H72O6þNH4 m/z
702.5673; found 702.5656 amu.
2923 (vs, C–H), 2853 (vs, C–H), 1743 (vs, CvO) cm21
.
HRMS (API): calcd for C51H88O6þNH4 m/z 814.6925;
found 814.6897 amu.
4.1.10. 2-Eicosapentaenoyl-1,3-dihexadecanoylglycerol
(2e). The procedure was identical to that for preparing 2a
using 1,3-dihexadecanoylglycerol 1e (400 mg, 0.703 mmol),
EPA (213 mg, 0.703 mmol), DMAP (34 mg, 0.28 mmol)
and EDCI (162 mg, 0.84 mmol) in dichloromethane
(2.0 mL). The product was afforded as a yellowish oil
(540 mg, 90% yield). 1H NMR d 5.41–5.33 (m, 10H,
vCH), 5.33–5.23 (m, 1H, CH2CHCH2), 4.29 (dd, J¼11.9,
4.3 Hz, 2H, CH2CHCH2), 4.14 (dd, J¼11.9, 5.9 Hz, 2H,
CH2CHCH2), 2.88–2.75 (m, 8H, vCCH2Cv), 2.33 (t,
J¼7.4 Hz, 2H, CH2COO in EPA), 2.30 (t, J¼7.6 Hz, 4H,
CH2COO), 2.16–2.01 (m, 4H, vCHCH2CH2 and CH3-
CH2CHv), 1.75–1.63 (m, 2H, CH2CH2COO in EPA),
1.66–1.53 (m, 4H, CH2CH2COO in hexadecanoic acid),
1.40–1.17 (m, 48H, CH2), 0.97 (t, J¼7.5 Hz, 3H, CH3 in
EPA) and 0.88 (t, J¼6.8 Hz, 6H, CH3) ppm. 13C NMR d
173.3 (2, aCvO), 172.6 (1, bCvO, EPA), 132.0 (1), 128.9
(1), 128.8 (1), 128.6 (1), 1283 (1), 128.2 (1), 128.1 (1), 128.0
(1), 127.8 (1), 127.0 (1), 69.0 (1), 62.0 (2), 34.0 (2), 33.6 (1),
31.9 (2), 29.7 (10), 29.6 (2), 29.5 (2), 29.4 (2), 29.3 (2), 29.1
(2), 26.5 (1), 25.6 (3), 25.5 (1), 24.8 (2), 24.7 (1), 22.7 (2),
4.1.8. 2-Eicosapentaenoyl-1,3-didodecanoylglycerol (2c).
The procedure was identical to that for preparing 2a using
1,3-didodecanoylglycerol 3c (350 mg, 0.766 mmol), EPA
(232 mg, 0.766 mmol), DMAP (38 mg, 0.31 mmol) and
EDCI (176 mg, 0.92 mmol) in dichloromethane (2.0 mL).
The product was afforded as a yellowish oil (523 mg, 92%
1
yield). H NMR d 5.41–5.33 (m, 10H, vCH), 5.33–5.23
(m, 1H, CH2CHCH2), 4.29 (dd, J¼11.9, 4.3 Hz, 2H,
CH2CHCH2), 4.13 (dd, J¼11.9, 5.9 Hz, 2H, CH2CHCH2),