D’YAKOVA et al.
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6.24–6.38 m (1H, 3′-H), 6.95–7.09 m (1H, 1′-H), 7.18–
7.34 s (1H, 6-H), 8.21–8.36 s (1H, NH).
280 mg (0.419 mmol) of compound I, 103.6 mg
(0.503 mmol) of N,N′-dicyclohexylcarbodiimide,
76.7 mg (0.629 mmol) of 4-dimethylaminopyridine,
and 54.9 mg (0.419 mmol) of 1,2-O-isopropylidene-
rac-glycerol (III) in 25 ml of methylene chloride was
stirred for 12 h. The mixture was treated with 12 ml of
water, the organic phase was separated, washed with
water (2×20 ml), dried over sodium sulfate, and evap-
orated under reduced pressure, and the residue was
purified by column chromatography on silica gel using
hexane–ethyl acetate (9:1) as eluent. Yield 253.2 mg
(77%), Rf 0.40 (A), mp 51–53°C (from hexane).
1H NMR spectrum (CDCl3), δ, ppm: 0.78–0.96 t (6H,
CH3), 1.17–1.34 m (48H, CH2), 1.34 s and 1.42 s (6H,
2-Me), 1.51–1.69 m (4H, β-CH2), 2.22–2.39 m (4H,
α-CH2), 2.58–2.74 m (4H, COCH2), 3.61–3.70 m
(1H, OCH), 4.04–4.38 m (8H, OCH2), 5.19–5.30 m
(1H, OCH).
6-{4-[1,3-Bis(palmitoyloxy)propan-2-yloxy]-1,4-
dioxobutoxy}hexyl 2′,3′-didehydro-3′-deoxythymi-
din-5′-yl succinate (IX) was synthesized from
60.0 mg (0.078 mmol) of compound II and 37.4 mg
(0.094 mmol) of ester VIII in the presence of
17.20 mg (0.141 mmol) of 4-dimethylaminopyridine
and 23.14 mg (0.113 mmol) of N,N′-dicyclohexylcar-
bodiimide. The product was isolated by chromatog-
raphy on silica gel using chloroform as eluent. Yield
22.8 mg (41%), Rf 0.50 (D), mp 77–79°C (from
1
chloroform). H NMR spectrum (CDCl3), δ, ppm:
0.79–0.97 t (6H, CH3), 1.21–1.39 m (48H, CH2),
1.53–1.70 m (16H, β-CH2, CH2), 1.90 s (3H, 5-CH3),
2.26–2.39 t (4H, α-CH2), 2.53–2.71 m (8H, COCH2),
4.08–4.25 m (4H, OCH2), 4.26–4.35 m (2H, 5′-H),
4.96–5.12 m (1H, 4′-H), 5.18–5.35 m (1H, OCH),
5.85–6.00 m (1H, 2′-H), 6.24–6.38 m (1H, 3′-H),
6.95–7.09 m (1H, 1′-H), 7.18–7.34 s (1H, 6-H), 8.21–
8.36 s (1H, NH).
Compounds VII, IX, and X were synthesized in
a similar way.
1,3-Bis(palmitoyloxy)propan-2-yl 2,3-dihydroxy-
propyl succinate (V). A solution of 270.0 mg
(0.010 mmol) of compound IV and 26 mg of Dowex
50WX2 in 2 ml of methanol was stirred for 2 h at
50°C, the exchanger was filtered off, the filtrate was
concentrated under reduced pressure, and the residue
was recrystallized from hexane. Yield 227.6 mg (90%),
Rf 0.31 (C), mp 58–60°C. 1H NMR spectrum (CDCl3),
δ, ppm: 0.73–0.89 t (6H, CH3), 1.12–1.28 m (48H,
CH2), 1.44–1.60 m (4H, β-CH2), 2.18–2.35 m (4H,
α-CH2), 2.52–2.68 m (4H, COCH2), 3.45–3.71 m
(2H, OCH2), 3.78–3.96 m (1H, OCH), 4.05–4.18 m
(4H, OCH2), 4.19–4.33 m (2H, OCH2), 5.09–5.26 m
(1H, OCH).
1,3-Bis(palmitoyloxy)propan-2-yl 2,3-bis(2′,3′-di-
dehydro-3′-deoxythymidin-5′-yloxy)propyl succi-
nate (X) was synthesized from 40.0 mg (0.054 mmol)
of compound V and 43.2 mg (0.108 mmol) of ester
VIII in the presence of 19.8 mg (0.162 mmol) of
4-dimethylaminopyridine and 26.8 mg (0.130 mmol)
of N,N′-dicyclohexylcarbodiimide. The product was
isolated by column chromatography on silica gel using
chloroform containing 2% of methanol as eluent. Yield
1
25.2 mg (58%), Rf 0.53 (E). H NMR spectrum
(CDCl3), δ, ppm: 0.74–0.92 t (6H, CH3), 1.14–1.32 s
(48H, CH2), 1.51–1.68 m (4H, β-CH2), 1.86–2.04 s
(6H, 5-CH3), 2.20–2.38 t (4H, α-CH2), 2.56–2.75 m
(12H, COCH2), 3.61–3.79 s (1H, OCH), 4.08–4.28 m
(12H, OCH2, 5′-H), 4.35–4.52 m (1H, OCH), 4.96–
5.11 m (2H, 4′-H), 5.1–5.32 m (1H, OCH), 5.80–
6.00 m (2H, 2′-H), 6.18–6.36 m (2H, 3′-H),
6.89–7.08 m (2H, 1′-H), 7.12–7.30 s (2H, 6-H), 8.20–
8.40 s (2H, NH).
1,3-Bis(palmitoyloxy)propan-2-yl 2′,3′-didehy-
dro-3′-deoxythymidin-5′-yl succinate (VII) was ob-
tained from 46.0 mg (0.070 mmol) of glycerolipid
derivative I and 15.3 mg (0.069 mmol) of nucleoside
VI in the presence of 17.2 mg (0.082 mmol) of
N,N′-dicyclohexylcarbodiimide and 12.8 mg
(0.105 mmol) of 4-dimethylaminopyridine. The prod-
uct was isolated by column chromatography on silica
gel using hexane–ethyl acetate (7:3) as eluent. Yield
41.3 mg (69%), Rf 0.26 (C), mp 120–122°C (from
1,3-Bis(palmitoyloxy)propan-2-yl 6-(2′,3′-dide-
hydro-3′-deoxythymidin-5′-yloxyphosphoryloxy)-
hexyl succinate (XII). Triethylammonium phospho-
nate XI, 55.4 mg (0.059 mmol), and nucleoside VI,
26.6 mg (0.119 mmol), were dried by evaporation of
their mixtures with 3 ml of pyridine. The reactants
were then dissolved in 5 ml of pyridine, 21.8 μl
(0.178 mmol) of pivaloyl chloride was added under
stirring at room temperature, and the mixture was
stirred for 15 min, diluted with chloroform (15 ml),
and washed with a 5% solution of sodium bisulfite
1
chloroform). H NMR spectrum (CDCl3), δ, ppm:
0.82–0.97 t (6H, CH3), 1.21–1.36 m (48H, CH2), 1.54–
1.69 m (4H, β-CH2), 1.88–2.05 s (3H, 5-CH3), 2.25–
2.40 m (4H, α-CH2), 2.58–2.74 m (4H, COCH2), 4.08–
4.53 m (6H, OCH2, 5′-H), 4.98–5.15 m (1H, 4′-H),
5.18–5.35 m (1H, OCH), 5.85–6.00 m (1H, 2′-H),
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 10 2011