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(2 × 25 mL), dried with Na2SO4, and concentrated. The crude
product was co-evaporated twice with toluene and then
dissolved in CH2Cl2 (10 mL) followed by addition of (S)-1-O-
hexadecyl-2-O-benzyl-glycerol (19)29 (283 mg, 0.70 mmol) and
4 Å molecular sieves. The suspension was stirred for 40 min after
which time the mixture was cooled to 0 °C and 5-phenyl-1H-
tetrazole (105 mg, 0.72 mmol) was added. The suspension was
stirred for 1.5 h and allowed to warm to room temperature. It
was then cooled to 0 °C again and 5.5 M t-BuOOH in dry hexane
(130 lL, 0.72 mmol) was added. The mixture was stirred for 1 h
and then quenched by the addition of 1 M aqueous Na2SO3
(20 mL) and saturated aqueous NaHCO3 (20 mL). The phases
were separated after 15 min stirring and the aqueous phase was
extracted with CH2Cl2 (3 × 20 mL). The combined organic
phases were washed with brine (25 mL), dried with MgSO4,
and concentrated. Purification by column chromatography
(EtOAc–hexane, 3:7, Rf 0.22) gave the benzyl protected
phosphatidylinositol as a mixture of two diastereomers. These
were dissolved in t-BuOH (20 mL) and 10% Pd/C (70 mg) was
added. The suspension was hydrogenated under 10 bar of H2 for
18 h, and then filtered and concentrated to give 176 mg (70%)
of 1. Rf 0.20 (CHCl3–MeOH–H2O, 65:25:4); dH (500 MHz,
CDCl3–CD3OD, 9:1): 4.15–3.98 (m, 4H), 3.50–3.40 (m, 5H),
3.39 (t, J = 9.1 Hz, 1H), 3.24 (t, J = 9.1 Hz, 1H), 2.12 (m, 1H),
1.94 (m, 1H), 1.59–1.48 (m, 3H), 1.37 (m, 1H), 1.36–1.27 (br
s, 26H), 0.89 (t, J = 6.8 Hz, 3H); dC (75 MHz, CDCl3–CD3OD,
9:1): 79.0 (J = 6.2 Hz), 77.2, 75.8 (J = 5.6 Hz), 71.8, 71.7, 71.0,
69.1 (J = 7.3 Hz), 68.6 (J = 6.2 Hz), 31.8, 29.6, 29.5, 29.4, 29.2,
29.2, 27.6, 27.3 (J = 1.3 Hz), 25.9, 22.6, 13.9; dP (202 MHz,
CDCl3–CD3OD, 9:1): −0.21; ESI HRMS calcd. for C25H50O9P
[M − H]− m/z 525.3192, found m/z 525.3148.
7 T. G. Cross, D. Scheel-Toellner, N. V. Henriquez, E. Deacon,
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1D-3-Deoxy-myo-inositol 1-[(R)-3-(hexadecyloxy)-2-
hydroxypropyl hydrogen phosphate] (2)
Phosphorylation of 5 (114 mg) was performed as described
above to give 79 mg (67%) of 2. Rf 0.17 (CHCl3–MeOH–H2O,
65:25:4); dH (500 MHz, CDCl3–CD3OD, 3:1): 4.24–4.21 (m,
1H), 4.10–3.94 (m, 5H), 3.87–3.75 (m, 3H), 3.58 (t, 9.2 Hz, 1H),
3.27–3.17 (m, 2H), 2.16–2.10 (m, 1H), 1.61–1.23 (br s, 29H),
0.89 (t, J = 6.8 Hz, 3H); dC (75 MHz, CDCl3–CD3OD, 3:1):
79.6 (J = 5.6 Hz), 77.4 (J = 3.6 Hz), 73.9, 72.5, 71.3, 70.9, 69.0
(J = 7.1 Hz), 67.9 (J = 4.4 Hz), 67.4 (J = 5.1 Hz), 31.4, 29.2,
29.1, 29.0, 29.0, 28.8, 25.5, 22.1, 13.2; dP (202 MHz, CDCl3–
CD3OD, 3:1): 1.18; ESI HRMS calcd. for C25H50O10P [M − H]−
m/z 541.3141, found m/z 541.3088.
1D-myo-Inositol 1-[(R)-3-(hexadecyloxy)-2-hydroxypropyl
hydrogen phosphate] (3)
Phosphorylation of 6 (158 mg) was performed as described
above to give 92 mg (66%) of 3. Rf 0.14 (CHCl3–MeOH–H2O,
65:25:4); dH (300 MHz, CDCl3–CD3OD, 1:1): 4.25–4.19
(m, 1H), 4.09–3.90 (m, 4H), 3.80 (t, J = 9.2 Hz, 1H), 3.66 (t,
J = 9.5 Hz, 1H), 3.53–3.37 (m, 5H), 3.23 (t, J = 9.2 Hz, 1H),
1.64–1.52 (m, 2H), 1.34–1.20 (br s, 26H), 0.89 (t, J = 6.6 Hz,
3H); dC (75 MHz, CDCl3–CD3OD–D2O, 65:25:4): 77.3, 76.2,
73.9, 72.1, 71.6, 71.3, 71.1, 70.7, 69.3, 67.1, 31.7, 29.5, 29.4, 29.4,
29.2, 29.1, 25.7, 22.4, 13.7; dP (202 MHz, CDCl3–CD3OD, 1:1):
0.05; ESI HRMS calcd. for C25H50O11P [M − H]− m/z 557.3091,
found m/z 557.3079.
19 (a) C. S. Poulsen and R. Madsen, J. Org. Chem., 2002, 67, 4441;
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26 C. Jaramillo, J.-L. Chiara and M. Martín-Lomas, J. Org. Chem.,
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Acknowledgements
Financial support from the Danish Academy of Technical
Services, LiPlasome Pharma A/S, and the Lundbeck Foundation
are gratefully acknowledged.
27 T. Trnka, M. Budešínský and M. Cerný, Carbohydr. Res., 1994, 259,
131.
28 O. Arjona, A. de Dios, J. Plumet and B. Saez, J. Org. Chem., 1995,
60, 4932.
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