C.D. Magnusson, G.G. Haraldsson / Tetrahedron 66 (2010) 2728–2731
2731
dichloromethane through a short column packed with silica gel.
25.5, 22.6, 20.5,18.3 (2),14.3 and 13.6 (2) ppm. IR
2964 (vs, C–H), 2876 (s, C–H), 1736 (vs, C]O) cm . HRMS (API):
n
max 3013 (s, C–H),
1
ꢀ1
The product was afforded as a yellowish oil (307 mg, 92% yield). H
NMR 5.44–5.33 (m, 10H, ]CH), 5.33–5.24 (m, 1H, CH CHCH ),
.30 (dd, J¼12.0, 4.4 Hz, 2H, CH CHCH ), 4.15 (dd, J¼12.0, 6.0 Hz,
H, CH CHCH ), 2.88–2.78 (m, 8H, ]CCH
C]), 2.34 (t, J¼7.5 Hz, 2H,
COO in EPA), 2.30 (t, J¼7.5 Hz, 4H, CH COO), 2.14–2.04 (m, 4H,
CCH CH and ]CCH CH
), 1.70 (quintet, J¼7.5 Hz, 2H,
CH CH COO in EPA), 1.69–1.60 (m, 4H, CH CH COO), 0.97 (t,
J¼7.5 Hz, 3H, CH in EPA) and 0.94 (t, J¼7.5 Hz, 6H, CH
NMR 173.1 (2), 172.6, 132.0, 129.0, 128.8, 128.6, 128.3, 128.2, 128.1,
28.0, 127.8, 127.0, 69.0, 62.0 (2), 35.9 (2), 33.6, 26.4, 25.6 (3), 25.5,
4.7, 20.5, 18.3 (2), 14.3 and 13.6 (2) ppm. IR max 3012 (s, C–H),
964 (vs, C–H), 2876 (s, C–H), 1736 (vs, C]O) cm . HRMS (API):
þH m/z 517.3524; found 517.3515 amu.
d
2
2
Calcd for C33H
50
O
6
þH m/z 543.3680; found 543.3655 amu.
4
2
2
2
2
2
2
4.1.9. 2-Docosahexaenoyl-1,3-dihexanoylglycerol 3c. The procedure
was identical to that for preparing 2b using DHA (236 mg,
0.718 mmol), DMAP (18 mg, 0.144 mmol) and EDAC (15 mg,
0.862 mmol) in dry dichloromethane (3 ml) to which was added
CH
2
2
]
2
2
2
3
2
2
2
2
13
3
3
) ppm.
C
1,3-dihexanoylglycerol 1c (207 mg, 0.718 mmol). The product was
1
d
afforded as a yellowish oil (404 mg, 94% yield). H NMR
d
5.44–5.32
1
2
2
(m, 12H, ]CH), 5.31–5.24 (m, 1H, CH
4.4 Hz, 2H, CH CHCH
), 4.15 (dd, J¼12.0, 6.0 Hz, 2H, CH
2.88–2.78 (m, 10H, ]CCH C]), 2.40–2.38 (m, 4H, CH CH
DHA), 2.31 (t, J¼7.5 Hz, 4H, CH COO), 2.11–2.04 (m, 2H,
CCH CH ),1.65–1.58 (m, 4H, CH CH COO),1.37–1.25 (m, 8H, CH ),
0.97 (t, J¼7.5 Hz, 3H, CH in DHA) and 0.89 (t, J¼6.8 Hz, 6H,
173.3 (2), 172.1, 132.0, 129.4, 128.6, 128.3 (2),
2
CHCH
2
), 4.30 (dd, J¼12.0,
CHCH ),
COO in
n
2
2
2
2
ꢀ1
2
2
2
Calcd for C31
H
48
O
6
2
]
2
3
2
2
2
4.1.6. 2-Eicosapentaenoyl-1,3-dihexanoylglycerol 2c. The procedure
3
13
was identical to that for preparing 2b using EPA (210 mg,
3
CH ) ppm. C NMR d
0
0
.693 mmol), DMAP (17 mg, 0.139 mmol) and EDAC (159 mg,
.832 mmol) in dry dichloromethane (3 ml) to which was added
128.2, 128.1 (2), 127.9, 127.8, 127.6, 127.0, 69.0, 62.0 (2), 34.0 (3), 31.2
(2), 25.6 (4), 25.5, 24.5 (2), 22.6, 22.3 (2), 20.5, 14.3 and 13.9
1
,3-dihexanoylglycerol 1c (200 mg, 0.693 mmol). The product was
(2) ppm. IR
n
max 3013 (s, C–H), 2959 (vs, C–H), 2872 (s, C–H), 1740
1
ꢀ1
afforded as a yellowish oil (360 mg, 91% yield). H NMR
m, 10H, ]CH), 5.33–5.24 (m, 1H, CH CHCH
), 4.15 (dd, J¼12.0, 6.0 Hz, 2H, CH
.88–2.76 (m, 8H, ]CCH
C]), 2.34 (t, J¼7.3 Hz, 2H, CH
COO), 2.14–2.04 (m, 4H, ]CCH
), 1.70 (quintet, J¼7.5 Hz, 2H, CH CH COO in EPA),
.65–1.58 (m, 4H, CH CH COO), 1.37–1.25 (m, 8H, CH ), 0.97 (t,
J¼7.5 Hz, 3H, CH in EPA) and 0.89 (t, J¼6.8 Hz, 6H, CH
NMR 173.2 (2), 172.6, 132.0, 128.9, 128.8, 128.6, 128.3, 128.2, 128.1,
28.0, 127.8, 127.0, 69.0, 62.1 (2), 34.0 (2), 33.6, 31.2 (2), 26.5, 25.6
3), 25.5, 24.7, 24.5 (2), 22.3 (2), 20.5, 14.3 and 13.9 (2) ppm. IR
013 (s, C–H), 2958 (vs, C–H), 2872 (s, C–H), 1739 (vs, C]O) cm
HRMS (API): Calcd for
þH m/z 573.4150; found
d
5.43–5.32
), 4.30 (dd, J¼12.0,
CHCH ),
COO in
CH
(vs, C]O) cm . HRMS (API): Calcd for C37
616.4572; found 616.4572 amu.
H
58
O
6
þNH
4
m/z
(
2
2
4
2
.4 Hz, 2H, CH
2
CHCH
2
2
2
2
2
Acknowledgements
EPA), 2.31 (t, J¼7.5 Hz, 4H, CH
2
2
2
and ]CCH CH
2
3
2
2
The University of Iceland Research Fund is acknowledged for
financial support, Novozyme AS in Denmark for the lipase and Olav
Thorstad of Pronova Biocare ASA in Norway for pure EPA and DHA.
Dr. Sigridur Jonsdottir and Dr. Sigurdur V. Smarason at University of
Iceland are acknowledged for high-resolution NMR and accurate
MS measurements.
1
2
2
2
13
3
3
) ppm.
C
d
1
(
3
n
max
ꢀ
1
.
35 56
C H O
6
References and notes
573.4135 amu.
1. Haraldsson, G. G.; Hjaltason, B. In Structured and Modified Lipids; Gunstone, F. D.,
Ed.; Marcel Dekker: New York, NY, 2001; pp 313–350.
. Hjaltason, B.; Haraldsson, G. G. In Modifying Lipids for Use in Food; Gunstone, F.
D., Ed.; Woodhead: Cambridge UK, 2006; Chapter 4, pp 56–79.
. Stansby, M. E. In Fish Oils in Nutrition; Stansby, M. E., Ed.; van Nostrand Rein-
hold: New York, NY, 1990; Chapter 10, pp 268–288.
4
.1.7. 1,3-Diacetyl-2-docosahexaenoylglycerol 3a. The procedure
2
3
4
was identical to that for preparing 2a using DHA (186 mg,
0
0
.568 mmol), DMAP (14 mg, 0.114 mmol) and EDAC (131 mg,
.686 mmol) in dry dichloromethane (2 ml) to which was added
. Nettleton, J. A. Omega-3 Fatty Acids and Health; Chapman and Hall: New York,
NY, 1995.
1,3-diacetylglycerol 1a (100 mg, 0.568 mmol). The product was
1
afforded as a yellowish oil (248 mg, 90% yield). H NMR
m, 12H, ]CH), 5.30–5.24 (m, 1H, CH CHCH
), 4.15 (dd, J¼12.0, 6.0 Hz, 2H, CH
.88–2.80 (m, 10H, ]CCH C]), 2.40–2.36 (m, 4H, CH CH
.11–2.04 (m, 2H, ]CCH CH ), 2.07 (s, 6H, CH COO) and 0.97 (t,
in DHA) ppm. C NMR 172.1, 170.3 (2), 131.9,
29.3, 128.4, 128.2, 128.1 (2), 127.9 (2), 127.8, 127.7,127.5, 126.9, 68.8,
d
5.44–5.30
), 4.29 (dd, J¼12.0,
CHCH ),
COO),
5. Lands, W. E. M. Fish, Omega-3 and Human Health, 2nd ed.; AOCS: Champaign, IL,
005.
2
(
2
2
6. Jumpsen, J.; Clandinin, M. T. Brain Development: relationship to Dietary Lipid and
4
2
2
.4 Hz, 2H, CH
2
CHCH
2
2
2
Lipid Metabolism; AOCS: Champaign, IL, 1995.
7. Haumann, B. F. Inform 1997, 8, 428–447.
2
2
2
8. Stoll, A. L. The Omega-3 Connection: the Groundbreaking Anti-depression Diet and
Brain Program; Simon & Schuster: New York, NY, 2001.
2
3
3
13
J¼7.5 Hz, 3H, CH
3
d
9. Horrobin, D. F. Schizophr. Res. 1998, 30, 193–208.
1
6
10. Lukiw, W. J.; Cui, J.-G.; Marcheselli, V. L.; Bodker, M.; Botkjaer, A.; Gotlinger, K.;
Serhan, C. N.; Bazan, N. G. J. Clin. Invest. 2005, 115, 2774–2783.
2.1 (2), 33.9, 25.5 (4), 25.4, 22.5, 20.6 (2), 20.4 and 14.2 ppm. IR
1
1
1. Hibbeln, J. R. Lancet 1998, 351, 1213.
2. Frasure-Smith, N.; Lesp e´ rance, F.; Julien, P. Biol. Psychiatry 2004, 55, 891–896.
13. Miura, S.; Ogawa, A.; Konishi, H. J. Am. Oil Chem. Soc. 1999, 76, 927–931.
4. Fomuso, L. B.; Akoh, C. C. J. Am. Oil Chem. Soc. 1998, 75, 405–410.
5. Christensen, M. S.; H o¨ y, C.-E.; Becker, C. C.; Redgrave, T. G. Am. J. Clin. Nutr. 1995,
1, 56–61.
16. Halldorsson, A.; Magnusson, C. D.; Haraldsson, G. G. Tetrahedron 2003, 59,
101–9109.
7. Haraldsson, G. G. In Handbook of Industrial Biocatalysis; Hou, C. T., Ed.; CRC,
n
max 3013 (vs, C–H), 2964 (s, C–H), 2875 (s, C–H), 1740 (vs,
ꢀ1
C]O) cm . HRMS (API): Calcd for C29
found 487.3073 amu.
H
42
O
6
þH m/z 487.3054;
1
1
6
4
.1.8. 1,3-Dibutanoyl-2-docosahexaenoylglycerol 3b. The procedure
9
was identical to that for preparing 2b using DHA (250 mg,
0
0
1
.761 mmol), DMAP (19 mg, 0.152 mmol) and EDAC (175 mg,
.913 mmol) in dry dichloromethane (3 ml) to which was added
Taylor and Francis Group: Boca Raton, 2005; Chapter 18, pp 18-1–18-21.
18. Haraldsson, G. G.; Halldorsson, A.; Kulås, E. J. Am. Oil Chem. Soc. 2000, 77,
1139–1145.
19. Berger, M.; Laumen, K.; Schneider, M. P. J. Am. Oil Chem. Soc. 1992, 69, 955–960.
0. Irimescu, R.; Furihata, K.; Hata, K.; Iwasaki, Y.; Yamane, T. J. Am. Oil Chem. Soc.
1,3-dibutanoylglycerol 1b (177 mg, 0.761 mmol). The product was
1
afforded as a yellowish oil (380 mg, 92% yield). H NMR
m, 12H, ]CH), 5.32–5.25 (m, 1H, CH CHCH
), 4.15 (dd, J¼12.0, 6.0 Hz, 2H, CH
.88–2.79 (m, 10H, ]CCH C]), 2.40–2.38 (m, 4H, CH CH
COO), 2.11–2.04 (m, 2H,
), 1.64 (sextet, J¼7.5 Hz, 4H, CH CH CH COO), 0.97 (t,
J¼7.5 Hz, 3H, CH in DHA) and 0.95 (t, J¼7.5 Hz, 6H, CH
NMR 173.1 (2), 172.1, 132.0, 129.4, 128.5, 128.3, 128.2, 128.0 (2),
27.9 (2), 127.8, 127.6, 127.0, 69.0, 62.0 (2), 35.9 (2), 34.0, 25.6 (4),
d
5.44–5.32
), 4.30 (dd, J¼12.0,
CHCH ),
COO in
2
(
4
2
2
2
2001, 78, 285–289.
.4 Hz, 2H, CH
2
CHCH
2
2
2
21. Irimescu, R.; Iwasaki, Y.; Hou, C. T. J. Am. Oil Chem. Soc. 2002, 79, 879–883.
2
2. Kawashima, A.; Shimada, Y.; Yamamoto, M.; Sugihara, A.; Nagao, T.; Kome-
mushi, S.; Tominaga, Y. J. Am. Oil Chem. Soc. 2001, 78, 611–616.
3. Kodali, D. R.; Tercyak, A.; Fahey, D. A.; Small, D. M. Chem. Phys. Lipids 1990, 52,
163–170.
2
2
2
DHA), 2.30 (t, J¼7.5 Hz, 4H, CH
CCH CH
2
2
]
2
3
3
2
2
13
24. Compton, D. L.; Vermillion, K. E.; Laszlo, J. A. J. Am. Oil Chem. Soc. 2007, 84, 343–348.
3
3
) ppm.
C
2
2
5. Laszlo, J. A.; Compton, D. L.; Vermillion, K. E. J. Am. Oil Chem. Soc. 2008, 85, 307–312.
d
¨
¨
6. Haraldsson, G. G.; Gudmundsson, B. O.; Almarsson, O. Tetrahedron 1995, 51,
1
941–952.