LETTER
Rapid Condensation of Lysophosphorylcholine and Fatty Acids
2017
HO
68, 3749. (i) Gugiu, B.; Salomon, R. G. Org. Lett. 2003, 5,
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CO2Me
(
(
(
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Lipid Res. 1977, 18, 548. (c) Diyizou, Y. L.; Genevois, A.;
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6
TBSCl
C3H4N2
95%
TBSO
CO2R
1969, 187, 520. (b) Gupta, C. M.; Radhakrishnan, R.;
Khorana, H. G. Proc. Natl. Acad. Sci. U.S.A. 1977, 74,
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Biochem. 1981, 113, 96. (d) Xia, J.; Hui, Y.-Z. Tetrahedron:
Asymmetry 1997, 8, 451.
7, R = Me
LiOH
4%
2e, R = H
9
Scheme 1 A method to obtain acid 2e
7) (a) Bruzic, K. S.; Salamónczyk, G.; Stec, W. J. J. Org.
Chem. 1986, 51, 2368. (b) Burgos, C. E.; Ayer, D. E.;
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Stawiꢀski, J. J. Org. Chem. 1989, 54, 1338. (d) Ali, S.;
Bittman, R. J. Org. Chem. 1988, 53, 5547. (e) Hébert, N.;
Just, G. J. Chem. Soc., Chem. Commun. 1990, 1497.
In summary, we have established a high-speed and opera-
tionally simple condensation of lyso-PC 1 and fatty acids
2
a–e by using 2,6-Cl C H COCl (5) and 1-methylimida-
2 6 3
zole, which were removed quite easily by chromatogra-
phy on silica gel. We believe that the present method is
applicable to other lysophosphorylcholines and fatty ac-
ids.
(
1
f) Ishihara, M.; Sano, A. Chem. Pharm. Bull. 1996, 44,
096. (g) Roodsari, F. S.; Wu, D.; Pum, G. S.; Hajdu, J. J.
Org. Chem. 1999, 64, 7727. (h) Xia, J.; Hui, Y.-Z. Chem.
Pharm. Bull. 1999, 47, 1659. (i) Ohlsson, J.; Magnusson, G.
Tetrahedron 2000, 56, 9975.
(
(
8) (a) Nicholas, A. W.; Khouri, L. G.; Ellington, J. C. Jr.;
Porter, N. A. Lipids 1983, 18, 434. (b) Bibak, N.; Hajdu, J.
Tetrahedron Lett. 2003, 44, 5875.
General Procedure for the Condensation (Table 2, Entry 2)
To a solution of 1 (55 mg, 0.11 mmol), acid 2a (0.069 mL, 62 mg,
9) Lindberg, J.; Ekeroth, J.; Konradsson, P. J. Org. Chem.
0
.22 mmol), and 1-methylimidazole (0.026 mL, 27 mg, 0.33 mmol)
2002, 67, 194.
in CH Cl (11 mL) was added 2,6-dichlorobenzoyl chloride (5,
2
2
(
10) (a) Delfino, J. M.; Stankovic, C. J.; Schreiber, S. L.;
0
.048 mL, 70 mg, 0.34 mmol). The solution was stirred at r.t. for 13
Richards, F. M. Tetrahedron Lett. 1987, 28, 2323.
h and concentrated to obtain an oil, which was purified by chroma-
(
b) Delfino, J. M.; Schreiber, S. L.; Richards, F. M.
tography (CH Cl –MeOH) to afford 3a (70 mg, 83%).
2
2
Tetrahedron Lett. 1987, 28, 2327.
(
(
11) Inanaga, J.; Hirata, K.; Saeki, H.; Katsuki, T.; Yamaguchi,
M. Bull. Chem. Soc. Jpn. 1979, 52, 1989.
Acknowledgment
12) The racemic lyso-PC 1 was conveniently prepared from
racemic glycidol in two steps according to the literature
This work was supported by a Grant-in-Aid for Scientific Research
from the Ministry of Education, Science, Sports, and Culture, Ja-
pan, and the Sasakawa Scientific Research Grant from The Japan
Science Society.
9
+
–
procedure: (i) POCl then [HO(CH ) NMe ] ·TsO ; (ii)
3
2 2
3
C H CO Cs.
1
5
31
2
(13) Makino, K.; Nakajima, N.; Hashimoto, S.; Yonemitsu, O.
Tetrahedron Lett. 1996, 37, 9077.
(
(
14) Due to the low solubility of lyso-PC 1, THF was omitted in
the preliminary study using 4.
References
15) Reaction was carried out until 1 was consumed completely
(
(
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1
by H NMR spectroscopy since separation of product 3a and
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2
2
142. (b) Berliner, J. A. Vasc. Pharmacol. 2002, 38, 187.
TLC analysis was useless for monitoring the progress of
reaction.
(
c) Podrez, E. A.; Poliakov, E.; Shen, Z.; Zhang, R.; Deng,
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f
MeOH): 1, 0.1–0.2; 2a–e, >0.8; 3a, 0.1–0.2; 3b, 0.1–0.2; 3c,
2002, 277, 38503. (d) Jerlich, A.; Schaur, R. J.; Pitt, A. R.;
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1-methylimidazole, 0.5; 1-butylimidazole, 0.6; and
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(
(
(17) Chromatography of a reaction mixture on silica gel was
conducted with CH Cl –MeOH (CH Cl only, then 5:1,
2
2
2
2
(b) Hébert, N.; Beck, A.; Lennox, R. B.; Just, G. J. Org.
finally 1:3). Excess 2a eluted very early, then DMAP,
followed rapidly by product 3a, though DMAP was slightly
more polar than 3a on TLC. Other by-product(s) derived
from the acid chloride (or simply the hydrolyzed acid) did
not interfere with the purification of 3a. In addition, CH Cl –
Chem. 1992, 57, 1777. (c) Yoneda, K.; Sasakura, K.;
Tahara, S.; Iwasa, J.; Baba, N.; Kaneko, T.; Matsuo, M.
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2
2
MeOH is a convenient solvent system for chromatography in
comparison with conventional CHCl –MeOH–H O because
3
2
of fast elution during chromatography, easy evaporation of
the eluent, and no contamination of silica gel impurity that is
frequently encountered with the latter solvent system.
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