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10.3, 9.4 Hz, 1H), 5.10–4.98 (m, 1H), 4.46 (ddd, J=10.1, 4.5, 2.1 Hz,
1H), 4.33 (dd, J=12.3, 4.6 Hz, 1H), 4.05 (ddd, J=16.1, 11.4, 3.9 Hz,
2H), 3.60–3.38 (m, 8H), 2.82–2.72 (m, 2H), 2.12–2.02 (m, 9H), 1.62–
1.52 (m, 2H), 1.27 (s, 30H), 0.89 ppm (t, J=6.7 Hz, 3H); 13C NMR
(75 MHz, CDCl3): d=170.5, 169.8, 83.5, 80.2, 72.0, 71.9, 71.1, 68.7,
68.0, 61.9, 61.6, 57.9, 31.9, 31.1, 29.7, 29.7, 29.7, 29.6, 29.5, 29.4,
26.1, 22.7, 20.69, 20.66, 20.6, 14.1 ppm; MS (EI): m/z: 682.5
[M+Na]+.
1-O-Hexadecyl-2-O-methyl-3-S-(2’-amino-2’-deoxy-b-d-glucopyra-
nosyl)-sn-glycerol (8): 23 (100 mg, 0.13 mmol) was directly dis-
solved in 33 wt% of MeNH2/EtOH (5 mL), and the resulting mixture
was heated at reflux and stirred overnight, and then concentrated
to dryness. The resulting residue was purified by flash chromatog-
raphy (CH2Cl2/MeOH, 3:1) to afford 8 as a white solid (37 mg,
56%); Rf =0.27 (CH2Cl2/MeOH, 3:1); [a]2D5 =À32.48 (c=0.1, MeOH);
1H NMR (300 MHz, CD3OD): d=4.41 (d, 1H, J=9.8 Hz, H-1), 3.88 (d,
J=12.0 Hz, 1H), 3.73–3.55 (m, 5H), 3.53–3.44 (m, 6H), 3.36 (d, J=
8.4 Hz, 1H), 2.97 (dd, J=13.7, 5.4 Hz, 1H, SCHa), 2.85 (dd, J=13.8,
5.4 Hz, 1H, SCHb), 2.70 (d, J=18.3 Hz, 1H, H-2), 1.58 (d, J=6.6 Hz,
2H), 1.32 (s, 33H, OCH2CH2(CH2)13CH3), 0.93 ppm (t, J=6.7 Hz, 3H,
CH2CH3); 13C NMR (75 MHz, CD3OD): d=87.8 (C-1), 82.3, 81.4, 78.9,
72.7, 72.1, 71.7, 63.0, 58.0, 57.7 (C-2), 49.9, 49.6, 49.3, 49.0, 48.7,
48.5, 48.2, 33.1, 31.9, 30.8, 30.6, 30.5, 27.3, 23.8, 14.5 ppm (CH2CH3);
ESI-HRMS: m/z [M+Na]+ calcd for C26H53NO6SNa+: 530.3491,
found: 530.3487.
1-O-Hexadecyl-2-O-methyl-3-S-(2’-amino-2’-deoxy-a-d-glucopyr-
anosyl)-sn-glycerol (9): A solution of 22 (100 mg, 0.15 mmol) in
MeOH (5 mL) at RT was treated with NaOMe (20 mg, 0.37 mmol) to
reach pH 9. The mixture was stirred at RT overnight, neutralized
with Amberlite IR120 H+ exchange resin, filtered, and concentrated
in vacuo to afford a white solid, which was redissolved in MeOH
(5 mL). The solution was treated with 10 wt% of Pd/C (20 mg) and
stirred for 2 h under an atmosphere of H2. The mixture was filtered
and concentrated to dryness, and the resulting residue was puri-
fied by flash chromatography (CH2Cl2/MeOH, 5:1) to afford 22 as
Phenyl 3,4,6-tri-O-acetyl-2-phthalimido-2-deoxy-1-thio-b-d-glu-
copyranoside (24): A solution of 21 (477 mg, 1.00 mmol) in CH2Cl2
(10 mL) at RT was treated with thiophenol (0.2 mL, 2.00 mmol) and
BF3·Et2O (0.5 mL, 4.00 mmol). After stirring at RT overnight, the re-
action mixture was washed with saturated aq NaCl, dried with
Na2SO4, and concentrated to dryness. The resulting residue was pu-
rified by flash chromatography (hexane/EtOAc, 3:1) to afford 24 as
a yellow syrup (390 mg, 74%); Rf =0.24 (hexane/EtOAc, 3:1);
1H NMR data are in agreement with those reported earlier.[26]
a white solid (62 mg, 81%); Rf =0.18 (CH2Cl2/MeOH, 5:1); [a]D25
=
44.68 (c=0.1, MeOH); 1H NMR (500 MHz, CD3OD): d=5.36 (d, 1H,
J=5.1 Hz, H-1), 3.95 (ddd, J=11.0, 5.5, 3.2 Hz, 1H), 3.81 (dd, J=
12.0, 2.3 Hz, 1H), 3.72 (dd, J=12.0, 5.4 Hz, 1H), 3.54 (ddd, J=15.4,
8.4, 4.8 Hz, 3H), 3.47–3.41 (m, 6H), 3.34–3.31 (m, 1H), 3.07 (dd, 1H,
J=10.4, 5.1 Hz, H-2), 2.84–2.76 (m, 2H, SCH2), 1.58–1.52 (m, 2H),
1.29 (d, J=17.5 Hz, 31H, OCH2CH2(CH2)13CH3), 0.88 ppm (t, J=
7.0 Hz, 3H, CH2CH3); 13C NMR (126 MHz, CD3OD): d=87.2 (C-1),
81.3, 74.9, 72.7, 72.3, 72.2, 62.5, 58.0, 56.7 (C-2), 33.3, 33.1, 30.8,
30.7, 30.6, 30.5, 27.2, 23.7, 14.4 ppm (CH2CH3); ESI-HRMS: m/z
[M+Na]+ calcd for C26H53NO6SNa+: 530.3491, found: 530.3510.
Hexadecyl p-toluenesulfonate (29): A solution of 28 (500 mg,
2.06 mmol) in dry pyridine (20 mL) was treated at 08C with p-TsCl
(2.0 g, 10.31 mmol). After stirring RT overnight, the reaction mixture
was concentrated to dryness. The resulting residue was purified by
flash chromatography (hexane/EtOAc, 10:1) to afford 29 as a white
solid (653 mg, 89%); Rf =0.23 (hexane/EtOAc, 10:1); 1H NMR
(300 MHz, CDCl3): d=7.79 (d, J=8.3 Hz, 2H), 7.34 (d, J=8.0 Hz,
2H), 4.02 (t, J=6.5 Hz, 2H), 2.44 (s, 3H), 1.68–1.55 (m, 2H), 1.34–
1.15 (m, 26H), 0.88 ppm (t, J=6.7 Hz, 3H).
2-Phthalimido-2-deoxy-b-d-glucopyranoside tetraacetate (21): A
solution of d-glucosamine·HCl (1.00 g, 4.64 mmol) in 1m aq NaOH
(10.0 mL) was treated with phthalic anhydride (2.96 g, 20.00 mmol).
After stirring at RT overnight, the mixture was concentrated to dry-
ness. The resultant syrup was redissolved in pyridine (10.0 mL), and
Ac2O (3.0 mL) and DMAP (50 mg) were added slowly. After stirring
overnight, the reaction mixture was concentrated to dryness, and
the resulting residue was purified by flash chromatography
(hexane/EtOAc, 1:1) to yield 21 as a yellow solid (1.48 g, 67%); Rf =
0.37 (hexane/EtOAc, 1:1); 1H NMR data are in agreement with
those reported earlier.[25]
3-(Hexadecyloxy)propan-1-ol (26): A solution of 1,3-propanediol
(192 mg, 2.52 mmol) in dry DMF (10 mL) was treated at RT with
NaH (14 mg, 0.60 mmol; dispersion in mineral oil), and the mixture
was stirred for 30 min. The solution was then further treated with
29 (200 mg, 0.50 mmol) in a single portion. The reaction mixture
was heated to 808C and stirred overnight. After quenching with
MeOH (1 mL), the mixture was concentrated to dryness. The result-
ing residue was purified by flash chromatography (hexane/EtOAc,
8:1) to afford 26 as a waxy solid (89 mg, 60%); Rf =0.19 (hexane/
1-O-Hexadecyl-2-O-methyl-3-S-(2’-phthalimido-2’-deoxy-3’,4’,6’-
tri-O-acetyl-b-d-glucopyranosyl)-sn-glycerol (23): A solution of 19
(100 mg, 0.29 mmol) and 21 (230 mg, 0.48 mmol) in dry CH2Cl2
(10 mL) was treated with BF3·Et2O (0.25 mL, 2.00 mmol). After stir-
ring at RT overnight, the reaction mixture was washed with saturat-
ed aq NaHCO3 and water, dried over Na2SO4, and concentrated in
vacuo. The residue was purified by flash chromatography (hexane/
EtOAc, 4:1) to afford 23 as a yellow solid (144 mg, 65%); Rf =0.17
(hexane/EtOAc, 4:1); 1H NMR (300 MHz, CDCl3): d=7.94–7.83 (m,
2H), 7.81–7.72 (m, 2H), 5.85 (dd, J=10.1, 9.2 Hz, 1H), 5.55 (d, J=
10.6 Hz, 1H), 5.21 (dd, J=23.3, 13.3 Hz, 1H), 4.38 (dd, J=16.6,
6.1 Hz, 1H), 4.34–4.25 (m, 1H), 4.19 (dd, J=12.3, 2.2 Hz, 1H), 3.90
(ddd, J=10.1, 4.8, 2.3 Hz, 1H), 3.52–3.44 (m, 3H), 3.37 (d, J=5.6 Hz,
5H), 2.93 (dd, J=13.7, 5.5 Hz, 1H), 2.74 (dd, J=13.7, 5.6 Hz, 1H),
2.16–2.08 (m, 3H), 2.03 (d, J=9.4 Hz, 3H), 1.88 (s, 3H), 1.60–1.48
(m, 2H), 1.26 (s, 29H), 0.89 ppm (t, J=6.7 Hz, 3H); 13C NMR
(75 MHz, CDCl3): d=170.7, 170.1, 169.5, 134.4, 123.5, 81.7, 79.6,
76.0, 71.7, 71.5, 70.8, 68.9, 62.4, 62.2, 57.7, 53.9, 31.9, 31.2, 29.7,
29.5, 29.4, 26.1, 22.7, 20.8, 20.6, 20.5, 14.1 ppm; MS (EI): m/z: 786.5
[M+Na]+.
1
EtOAc, 8:1); H NMR (300 MHz, CDCl3): d=3.79 (dd, J=10.7, 5.3 Hz,
2H), 3.62 (t, J=5.7 Hz, 2H), 3.44 (t, J=6.6 Hz, 2H), 1.89–1.79 (m,
2H), 1.65–1.51 (m, 2H), 1.27 (s, 26H), 0.89 ppm (t, J=6.7 Hz, 3H).
3-(Hexadecyloxy)propan-1-O-(2’-phthalimido-2’-deoxy-3’,4’,6’-tri-
O-acetyl-b-d-glucopyranosyl)-sn-glycerol (27): A solution of 24
(56 mg, 0.17 mmol), 26 (89 mg, 0.17 mmol) and NIS (69 mg,
0.30 mmol) in dry CH2Cl2 (10 mL) was treated with AgOTf (8 mg,
0.03 mmol). After stirring at RT overnight, the reaction mixture was
washed with saturated aq NaHCO3 and water, dried over Na2SO4,
and concentrated to dryness. The residue was purified by flash
chromatography (hexane/EtOAc, 4:1) to afford 27 as a yellow solid
(53 mg, 45%); Rf =0.18 (hexane/EtOAc, 4:1); 1H NMR (300 MHz,
CDCl3): d=7.94–7.65 (m, 4H), 5.81 (dd, J=10.7, 9.1 Hz, 1H), 5.36 (d,
J=8.5 Hz, 1H), 5.27–5.05 (m, 1H), 4.41–4.25 (m, 2H), 4.22–4.11 (m,
1H), 3.96–3.81 (m, 2H), 3.69–3.47 (m, 1H), 3.27–3.15 (m, 2H), 3.13–
2.94 (m, 2H), 2.18–2.06 (m, 3H), 2.04 (d, J=3.0 Hz, 3H), 1.91–1.79
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ChemMedChem 2013, 8, 511 – 520 518