Synthesis of Ceramide
J. Chin. Chem. Soc., Vol. 54, No. 5, 2007 1377
The deprotected product 2 was dissolved in a solution of
Received February 16, 2007.
3
NEt and THF (1 mL, V/V 2:3). To this solution was added
the solution of NHS-ester (32 mg, 0.09 mmol) in THF (0.6
mL), prepared from palmitic acid according to Kim’s pro-
REFERENCES
o
cedure. It was stirred under gentle reflux at 80 C for 12 h.
1
2
. Seino, K.-I.; Motohashi, S.; Fujisawa, T.; Nakayama, T.;
Taniguchi, M. Cancer Sci. 2006, 97, 802-807.
After cooling to rt, a solution of DMAP (72 mg, 0.53
mmol), triethyl amine (168 mL, 1.2 mmol) and acetic anhy-
dride (178 mL, 1.9 mmol) in THF (1 mL) was added. It was
refluxed for 1 h followed by cooling to rt and a pale yellow
. Zhou, D.; Matnner, J.; Cantu III, C.; Schrantz, N.; Yin, N.;
Gao, Y.; Sagiv, Y.; Hudspeth, K.; Wu, Y.-P.; Yamashita, T.;
Teneberg, S.; Wang, D.; Proial, R. L.; Levery, S. B.; Savage,
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solution was obtained. The starting material 3 (R
consumed, while the product 4 (R = 0.21) was detected on
TLC (EtOAc/n-hexane 1:4) by staining with the vapor of I
f
= 0) was
f
1
789.
2
.
3
. Nieda, M.; Okai, M.; Tazbirkova, A.; Lin, H.; Yamaura, A.;
Ide, K.; Abraham, R.; Juji, T.; Macfarlane, D. J.; Nicol, A. J.
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The reaction was terminated by the addition of cold water
followed by extraction with EtOAc (3 × 3 mL). The organic
layer was washed with satd. NaHCO
3
(aq), 5% HCl and
4
followed by filter-
4. Koch, M.; Stronge, V. S.; Shepherd, D.; Gadola, S. D.;
Mathew, B.; Ritter, G.; Fersht, A. R.; Besra, G. S.; Schmidt,
R. R.; Jones, E. Y.; Cerundolo, V. Nat. Immunol. 2005, 6,
aqueous NaCl, and was dried by Na SO
2
ing through celite. After concentration under reduced pres-
sure, the residue was purified with column chromatography
using EtOAc/n-hexane 1:5 to provide the colorless oil-like
product 4 in 49% yield (42 mg). This was further purified
with normal-phase HPLC (Agillent 1100), equipped with a
sample loop (500 mL), semipreparative column (9.4 ´ 250
mm ZORBAX SIL, 5 mm material), eluents: EtOAc/n-hex-
ane 1:5, flow rate: 3 mL/min and detection of Refractive In-
dex. A white-oil product corresponding to the retention
time of 32.5 min in the chromatogram was obtained in 51%
8
19-826.
5. Zajonc, D. M.; Cantu III, C.; Mattner, J.; Zhou, D.; Savage, P.
B.; Bendelac, A. ; Wilson, I. A.; Teyton, L. Nat. Immunol.
2
005, 6, 810-818.
6
. De Jonghe, S.; Vaan Overmeire, I.; Van Calenbergh, S.;
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8
. Fan, G.-T.; Pan, Y.-I.; Lu, K.-C.; Cheng, Y.-P.; Lin, W.-C.;
Lin, S.; Lin, C.-H.; Wong, C.-H.; Fang, J.-M.; Lin, C.-C. Tet-
rahedron 2005, 61, 1855-1862.
yield (20 mg). Anal. C40
ESI+Q-TOF MS, M = 681.6 (m/z), [M+H] = 682.4; H-
NMR (500 MHz, C ) d 0.85 (t, J = 7.0 Hz, 6H), 1.22-1.26
m, 46H), 1.61-1.64 (m, 6H), 2.02 (s, 6H), 2.05 (s, 3H),
7
H75NO calcd mass: 682.0 amu,
+
1
6
D
6
9
. Chiu, H.-Y.; Tzou, D.-L.; Patkar, L. N.; Lin, C.-C. J. Org.
Chem. 2003, 68, 5788.
(
2
4
.18 (t, J = 7.5 Hz, 2H), 3.96 (dd, J = 2.0, J = 11.5 Hz, 1H),
.27 (dd, J = 4.5, J = 11.5 Hz, 1H), 4.46 (m, 1H), 4.90 (d, J
1
0. Plettenburg, O.; Vera Bodmer-Narkevitch, V.; Wong, C.-H.
J. Org. Chem. 2002, 67, 4559-4564.
=
9.5 Hz, 1H), 5.08 (dd, J = 2, J = 8.3 Hz, 1H), 5.91 (d, J =
1
1. Luo, S.-Y.; Kulkarni, S. S.; Chou, C.-H.; Liao, W.-M.; Hung,
1
3
9
.5 Hz, 1H); C-NMR (125 MHz, C
CH ), 20.8 (CH ), 21.0 (CH ), 22.7 (CH
5.6 (CH ), 28.0 (CH ), 29.2 (CH ), 29.3 (CH
), 29.6 (CH ), 29.7 (CH ), 31.9 (CH ), 36.7 (CH
7.4 (CH), 62.9 (CH ), 71.9 (CH), 73.0 (CH), 170.1 (C),
70.9 (C), 171.1 (C), 172.8 (C).
6
D
6
) d 14.1 (CH
), 25.5 (CH
), 29.4
),
3
), 20.7
S.-C. J. Org. Chem. 2006, 71, 1226-1229.
12. Goff, R.-D.; Gao, Y.; Mattner, J.; Zhou, D.; Yin, N.; Cantu
III, C.; Teyton, L.; Bendelac, A.; Savage, P. B. J. Am. Chem.
Soc. 2004, 126, 13602-13603.
(
3
3
3
2
2
),
2
2
2
2
2
(
CH
2
2
2
2
2
1
3. Ndonye, R. M.; Izmirian, D. P.; Dunn, M. F.; Yu, K. O. A.;
Porcelli, S. A.; Khurana, A.; Kronenberg, M.; Richardson, S.
K.; Howell, A. R. J. Org. Chem. 2005, 70, 10260-10270.
4. Kim, S.; Song, S.; Lee, T.; Jung, S.; Kim, D. Synthesis 2004,
4
1
2
1
1
6
, 847-850.
ACKNOWLEDGMENT
5. Xia, C. F.; Yao, Q. J.; Schumann, J.; Rossy, E.; Chen, W. L.;
Zhu, L. Z.; Zhang, W. P.; De Libero, G.; Wang, P. G. Bioorg.
Med. Chem. Lett. 2006, 16, 2195-2199.
We thank the National Science Council of Taiwan for
providing financial support (NSC-95-2113-M-007-039).
16. (a) Brik, A.; Wu, C. Y.; Wong, C. H. Org. Biomol. Chem.