SYNTHESIS OF CATIONIC CHOLESTEROL DERIVATIVES
1191
water (2 25 ml), and dried with Na SO . The solvent OCHCH C=CH), 2.66 m (4H, OCOCH CH OCO),
2
4
2
2
2
+
+
was evaporated, the residue was subjected to
chromatography (eluent chloroform methanol, 25: 1).
3.35 s [6H, N (CH ) ], 3.78 m [2H, CH N (CH ) ],
4.00 4.34 m [4H, HOCH CH N (CH ) ], 4.58 m
3 2 2 3 2
+
2
2
3 2
Yield 0.74 g (89%), R 0.64 (B), mp 42 43 C.
H NMR spectrum, , ppm: 0.68 s (3H, CH3),
(1H, OCOCH), 5.35 m (1H, C=CH). Mass spec-
f
1
+
trum, m/z: 602.5 [M I] . C H IINO . Calculated:
37
64
5
0
6
.86 d (3H, CH , J 6.8 Hz), 0.89 d (3H, CH , J
602.9.
3
3
.7 Hz), 1.01 s (3H, CH ), 1.03 1.61 m (21H,
3
N-[(3 -Cholesteryloxy)syccinyl]piperazine (VI).
A solution of 0.45 g (1 mmol) of cholesteryl hydro-
succinate (I), 0.18 g (2 mmol) of piperazine, 1 g of
dicyclohexylcarbodiimide in a mixture of 11 ml
acetonitrile and 8 ml of chloroform was heated to
cholesteryl), 1.81 2.03 m (5H, cholesteryl), 2.20
.30 m (8H, OCHCH C=CH, 2NCH ), 2.66 m (4H,
2
2
3
OCOCH CH OCO), 4.56 m (1H, OCOCH), 5.31 m
2
2
+
(
1H, C=CH). Mass spectrum, m/z: 558.4 M .
C H NO . Calculated: M 557.8.
3
5
59
4
35 C for 2 h. The residue of dicyclohexylurea was
N,N,N-trimethyl[2-(3 -cholesteryloxy)syccinyl-
oxyethyl]ammonium iodide (IV). A solution of
.080 g (0.1 mmol) of tertiary amine III in 3 ml of
DMSO was heated for 6 h to 65 C with 0.3 ml
0.4 mmol) of methyl iodide. The reaction mixture
filtered off and washed with acetonitrile. The solution
was evaporated, the residue was subjected to
0
chromatography (eluent dichloromethane methanol,
1
30: 1). Yield 0.130 g (27%), R 0.43 (C). H NMR
f
(
spectrum, , ppm: 0.68 s (3H, CH ), 0.86 d (3H,
3
was diluted with 30 ml of chloroform, washed with
water (2 10 ml), and dried with Na SO . The solvent
CH , J 6.8 Hz), 0.89 d (3H, CH , J 6.8 Hz), 1.01 s
3
3
(3H, CH ), 1.03 1.61 m (21H, cholesteryl), 1.81
2
4
3
was evaporated, the residue was subjected to
2.03
OCHCH C=CH,
m
(5H, cholesteryl), 2.25 br.d (2H,
Hz), 2.58 br.s (4H,
OCOCH CH OCO), 2.81 m (4H, 2CH NH), 3.49 m
chromatography (eluent chloroform methanol, 25: 1).
J
9
2
1
Yield 0.031 g (32%), R 0.34 (Å). H NMR spectrum,
f
2
2
2
,
ppm: 0.68 s (3H, CH ), 0.86 d (3H, CH , J
(4H, 2CH NCO), 4.55 m (1H, OCOCH), 5.30 m
(1H, C=CH). Mass spectrum, m/z: 577.3 [M+Na] .
3
3
2
+
6
.8 Hz), 0.89 d (3H, CH , J 6.7 Hz), 1.01 s (3H,
3
CH ), 1.03 1.61 m (21H, cholesteryl), 1.81 2.03 m
3
(
5H, cholesteryl), 2.30 m (2H, OCHCH C=CH),
REFERENCES
2
2
.66 m (4H, OCOCH CH OCO), 3.45 s [9H,
2 2
+
+
N(CH ) ], 3.49 m (2H, OCOCH2CH2N ), 3.92 m
1. Lasic, D.D., Liposomes in Gene Delivery, New York:
CRC Press, 1997, pp. 3 13.
2. Miller, A.D., Angew. Chem. Int. Ed., 1998, vol. 37,
no. 7, pp. 1768 1785.
3
3
+
(
2H, CH N ), 4.58 m (1H, OCOCH), 5.35 m (1H,
2
+
C=CH). Mass spectrum, m/z: 572.1 [M I] .
C H INO . Calculated: M 572.8.
3
7
62
4
3
. Konstantinova, I.D. and Serebrennikova, G.A., Usp.
Khim., 1996, vol. 65, no. 6, pp. 581 598.
N,N-Dimethyl-N-2-hydroxyethyl[2-(3 -choles-
teryloxy)syccinyloxyethyl]ammonium iodide (V). A
solution of 0.180 g (0.25 mmol) of tertiary amine III
in 9 ml of acetone was heated to 65 C for 3 h with
4
. Maslov, M.A., Sycheva, E.V., Morozova, N.G., and
Serebrennikova, G.A., Izv. Akad. Nauk, Ser. Khim.,
2
000, no. 3, pp. 485 500.
0
.2 ml (0.6 mmol) of 2-bromoethanol and 0.60 g of
5. Singhal, A. and Huang, L., Gene Therapeutics:
Methods and Applications of Direct Gene Transfer,
Wolff, J.A., Ed., Boston: Birknauser, 1994.
6. Konstantinova, T.V., Klykov, V.N., and Serebrenni-
kova, G.A., Bioorgan. Khimiya, 2001, vol. 27, no. 6,
pp. 459 462.
sodium iodide. The residue after removal of the
solvent was subjected to chromatography eluting in
succession with chloroform and chloroform methanol
mixture (25: 1). Yield 0.135 g (57%), R 0.52 (C).
f
1
HNMR spectrum, , ppm: 0.68 s (3H, CH ), 0.86 d
3
7
. Hughes, J.A., Aronsohn, A.J., Avrutskaya, A.V., and
Juliano, R.L., Pharm. Res., 1996, vol. 13, no. 9,
pp. 404 407.
(
3H, CH , J 6.8 Hz), 0.89 d (3H, CH , J 6.7 Hz),
3
3
1
1
.01 s (3H, CH ), 1.03 1.61 m (21H, cholesteryl),
3
.81 2.03 m (5H, cholesteryl), 2.30 m (2H,
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 38 No. 8 2002