A R T I C L E S
Yin et al.
(hexanoylamino)-â-D-glucopyranoside (15). Freshly filed zinc and
cadmium (excess) were added to a solution of 14 (0.90 g, 0.62 mmol)
in acetic acid. The mixture was sonicated for 2 h. Insoluble materials
were removed by filtration, and the filtrate was concentrated in vacuo.
The residue was dissolved in ethyl acetate (100 mL), washed with
saturated NaHCO3 aqueous solution (100 mL) and brine (100 mL),
dried (MgSO4), and concentrated. The residue was dissolved in CH2-
Cl2 (100 mL), and hexanoic anhydride (290 µL, 1.24 mmol) and
pyridine (250 µL, 3.10 mmol) were added to the solution. The mixture
was stirred for 2 h, washed with 5% HCl (100 mL) and brine (100
mL), dried (MgSO4), and concentrated. SiO2 chromatography (ethyl
acetate/hexanes 1:4) was performed to afford the product as a clear oil
6H), 1.94-1.81 (m, 2H), 1.61-1.55 (m, 2H), 1.54-1.43 (m, 6H), 1.30-
1.12 (m, 16H), 0.89-0.82 (m, 12H). 13C NMR (CDCl3) δ 174.06,
173.77, 173.52, 173.05, 154.89, 154.36, 135.65 (d, J ) 6.4 Hz), 135.59
(d, J ) 6.9 Hz), 135.33 (d, J ) 6.0 Hz), 135.22 (d, J ) 6.4 Hz), 135.23,
135.03, 129.32, 129.22, 128.14, 129.09, 128.84, 128.70, 128.66, 128.33,
128.23, 100.76, 96.01 (d, J ) 6.9 Hz), 73.65 (d, J ) 6.0 Hz), 73.19 (d,
J ) 2.3 Hz), 72.69 (d, J ) 5.0 Hz), 71.38, 70.50, 70.23 (d, J ) 5.5
Hz), 70.12 (d, J ) 5.5 Hz), 69.89, 69.88, 69.86, 69.83, 69.82, 69.62,
66.35, 66.04, 53.49, 52.00 (d, J ) 8.2 Hz), 36.65, 36.37, 34.03, 33.99,
31.70, 31.38, 31.35, 31.18, 25.48, 25.15, 24.56, 24.31, 22.49, 22.47,
22.41, 22.34, 14.09, 14.03, 14.00, 13.97. 31P NMR (CDCl3) δ -1.75,
-3.11. HRFAB-MS (thioglycerol + Na+ matrix) m/e ([M + Na]+)
1543.6241 (100%); calcd 1543.6246.
1
(0.43 g, 0.31 mmol, 50%). H NMR (CDCl3) δ 7.40-7.26 (m, 20H),
5.84 (d, J ) 8.3 Hz, 1H), 5.25-5.02 (m, 6H), 4.99-4.92 (m, 4H),
4.86 (t, J ) 9.8 Hz, 1H), 4.76 (d, J ) 8.3 Hz, 1H), 4.49 (d, J ) 11.7
Hz, 1H), 4.32 (q, J ) 9.3 Hz, 1H), 4.23 (dd, J ) 11.7, 5.4 Hz, 1H),
4.12 (d, J ) 8.3 Hz, 1H), 3.93-3.86 (m, 2H), 3.72 (q, J ) 8.3 Hz,
1H), 3.58 (dt, J ) 9.8, 3.4 Hz, 1H), 3.44-3.42 (m, 1H), 3.35 (dd, J )
11.7, 3.9 Hz, 1H), 2.33 (t, J ) 7.3 Hz, 2H), 2.21-2.02 (m, 6H), 1.66-
1.34 (m, 8H), 1.39-1.12 (m, 16H), 0.91-0.06(m, 21H), 0.09 (s, 3H),
0.06 (s, 3H), -3.86, -5.02. 13C NMR (CDCl3) δ 178.63, 173.83,
173.78, 173.01, 154.85, 154.45, 135.54 (d, J ) 6.8 Hz), 135.48 (d, J
) 7.3 Hz), 135.20, 135.17, 129.18, 128.73, 128.69, 128.58, 128.51,
128.46, 128.13, 128.08, 100.79, 96.42, 73.70 (d, J ) 6.0 Hz), 73.13,
72.57, 72.52, 72.32, 72.03, 70.32, 69.96, 69.95, 69.90, 67.79, 65.99,
56.13, 56.87, 36.87, 36.70, 34.18, 34.10, 33.93, 31.61, 31.52, 31.37,
31.34, 31.22, 25.90, 25.37, 25.35, 24.62, 24.60, 24.28, 22.47, 22.45.
22.43, 22.36,17.93, 14.07, 14.02, 13.98, -3.86, -5.02. 31P NMR
(CDCl3) δ -1.76. HRFAB-MS (thioglycerol + Na+ matrix) m/e ([M
+ Na]+) 1397.6492 (56.3%); calcd 1397.6506.
4-O-(Benzyloxycarbonyl)-6-O-[6-O-(benzyloxycarbonyl)-4-O-[bis-
(benzyloxy)phosphoryl]-2-deoxy-3-O-hexanoyl-2-(hexanoylamino)-
â-D-glucopyranosyl]-1-O-[bis(benzyloxy)phosphoryl]-2-deoxy-3-O-
hexanoyl-2-(hexanoylamino)-r-D-glucopyranose (16). As described
for 13, compound 15 (0.43 g, 0.31 mmol) was treated with a 49%
aqueous solution of HF to give 4-O-(benzyloxycarbonyl)-6-O-[6-O-
(benzyloxycarbonyl)-4-O-[bis(benzyloxy)phosphoryl]-2-deoxy-3-O-
hexanoyl-2-(hexanoylamino)-â-D-glucopyranosyl]-2-deoxy-3-O-hexanoyl-
2-(hexanoylamino)-D-glucopyranose (0.26 g, 0.21 mmol, 68%) as a
colorless oil.1H NMR (CDCl3) δ 7.39-7.23 (m, 20H), 5.82 (d, J )
7.8 Hz, 1H), 5.75 (d, J ) 9.3 Hz, 1H), 5.37 (dd, J ) 10.3, 8.8 Hz,
1H), 5.30 (dd, J ) 10.7, 9.8 Hz, 1H), 5.20 (d, J ) 3.4 Hz, 1H), 5.16-
5.10 (m, 5H), 4.98-4.90 (m, 5H), 4.81 (d, J ) 8.3 Hz, 1H), 4.75 (t, J
) 9.8 Hz, 1H), 4.49 (dd, J ) 12.2, 2.5 Hz, 1H), 4.42-4.38 (m, 1H),
4.27-4.18 (m, 3H), 4.13-4.09 (m, 1H), 3.80-3.77 (m, 1H), 3.58-
3.46 (m, 3H), 2.21-2.05 (m, 8H), 1.60-1.43 (m, 8H), 1.34-1.12 (m,
16H), 0.92-0.82 (m, 12H). 13C NMR (CDCl3) δ 174.33, 173.97,
173.68, 173.12, 154.95, 154.58, 135.56 (d, J ) 6.9 Hz), 135.49 (d, J
) 7.6 Hz), 135.24, 135.18, 100.83, 91.36, 73.75 (d, J ) 6.1 Hz), 72.80,
72.60, 72.56, 72.15, 70.95, 70.26, 69.98, 69.94, 69.92, 69.89, 69.87,
54.74, 52.24, 36.76, 36.75, 34.16, 33.98, 31.56, 31.51, 31.36, 31.27,
25.39, 25.35, 24.60, 24.38, 22.49, 22.40, 14.10, 14.05, 14.02. 31P NMR
(CDCl3) δ -1.92. HRFAB-MS (thioglycerol + Na+ matrix) m/e ([M
+ Na]+) 1283.5652 (100%); calcd 1283.5644. As in the preparation
of 12, 4-O-(benzyloxycarbonyl)-6-O-[6-O-(benzyloxycarbonyl)-4-O-
[bis(benzyloxy)phosphoryl]-2-deoxy-3-O-hexanoyl-2-(hexanoylamino)-
â-D-glucopyranosyl]-2-deoxy-3-O-hexanoyl-2-(hexanoylamino)-D-glu-
copyranose (260 mg, 0.21 mmol) was treated with 5-phenyl-1H-
tetrazole (59 mg, 0.41 mmol), dibenzyl diisopropylphosphoramidite
(140 µL, 0.41 mmol), and then H2O and MMPP (202 mg, 0.41 mmol)
to afford 16 (243 mg, 0.16 mmol, 76%) as a clear oil. 1H NMR (CDCl3)
δ 7.40-7.25 (m, 30H), 6.32 (d, J ) 8.8 Hz, 1H), 5.63 (dd, J ) 5.4,
3.9 Hz, 1H), 5.59 (d, J ) 8.3 Hz, 1H), 5.17-4.93 (m, 14H), 4.84 (t, J
) 9.8 Hz, 1H), 4.51 (dd, J ) 11.72, 2.0 Hz, 1H), 4.32 (q, J ) 9.3 Hz,
1H), 3.96-3.88 (m, 2H), 3.77 (d, J ) 11.2 Hz, 1H), 3.38 (ddd, J )
7.3, 5.4, 1.5 Hz, 1H), 3.32 (dd, J ) 12.7, 4.4 Hz, 1H), 2.20-2.09 (m,
2-Deoxy-6-O-[2-deoxy-3-O-hexanoyl-2-(hexanoylamino)-â-D-glu-
copyranosyl]-3-O-hexanoyl-2-(hexanoylamino)-r-D-glucopyranose
1,4′-Bisphosphate (2). Compound 16 (240 mg, 0.16 mmol) was
dissolved in THF (20 mL) and transferred to a hydrogenation vessel.
Palladium on carbon (10%, 100 mg) was added to the vessel. The vessel
was subjected to H2 (200 psi) at room temperature for 8 h. The catalyst
was removed via filtration through a Celite pad, and solvent was
removed in vacuo. The residue was lyophilized from a water solution
1
to give 5 (117 mg, 0.13 mmol, 81%) as a white powder. H NMR
(CD3OD) δ 5.48-5.45 (m, 1H), 5.25 (t, J ) 9.3 Hz, 1H), 5.17 (t, J )
10.8 Hz, 1H), 4.74 (d, J ) 8.3 Hz, 1H), 4.24-4.23 (m, 1H), 4.15 (d,
J ) 10.7 Hz, 1H), 4.08-4.01 (m, 2H), 3.90-3.79 (m, 4H), 3.59 (t, J
) 9.8 Hz, 1H), 3.52-3.51 (m, 1H), 2.41-2.25 (m, 4H), 2.23-2.11
(m, 4H), 1.63-1.53 (m, 8H), 1.36-1.24 (m, 16H), 0.93-0.89 (m, 12H).
13C NMR (CD3OD) δ 176.85, 176.54, 175.34, 175.94, 102.64, 96.48
(d, J ) 4.1 Hz), 76.81, 74.59, 74.55, 74.11, 69.42, 69.16, 62.04, 55.54,
53.31 (d, J ) 7.6 Hz), 37.55, 37.11, 35.30, 35.11, 32.79, 32.71, 32.63,
32.59, 26.84, 26.72, 25.86, 25.53, 23.63, 23.60, 23.57, 14.50, 14.42.
31P NMR (CD3OD) δ 3.88, 2.02. HRFAB-MS (thioglycerol + Na+
matrix) m/e ([M + Na]+) 915.3608 (100%); calcd 915.3633. Anal.
Calcd for C36H66N2O19P2: C, 48.43; H, 7.45. Found: C, 48.59; H, 7.46.
3-O-Acetyl-6-O-[3-O-acetyl-2-acetamino-2-deoxy-â-D-glucopyra-
nosyl]-2-acetamino-2-deoxy-r-D-glucopyranose 1,4′-Bisphosphate
1
(1). H NMR (CD3OD) δ 5.50-5.49 (m, 1H), 5.22 (t, J ) 9.8 Hz,
1H), 5.15 (dd, J ) 10.7, 9.3 Hz, 1H), 4.77 (d, J ) 8.3 Hz, 1H), 4.24-
4.20 (m, 1H), 4.14 (dt, J ) 10.7, 2.9 Hz, 1H), 4.08 (d, J ) 11.7 Hz,
1H), 4.04-4.01 (m, 1H), 3.90-3.78 (m, 4H), 3.58 (t, J ) 9.3 Hz, 1H),
3.51-3.50 (m, 1H), 2.05 (s, 3H), 2.03 (s, 3H), 1.96 (s, 3H), 1.93 (s,
3H). 13C NMR (CD3OD) δ 174.19, 173.80, 172.75, 172.39, 102.45,
96.23 (d, J ) 4.8 Hz), 76.75, 74.96, 74.55, 74.44, 74.03, 69.51, 69.25,
62.01, 55.80, 53.50 (d, J ) 7.6 Hz), 23.16, 22.78, 21.25, 21.13. 31P
NMR (CD3OD) δ 3.85, 2.15. HRFAB-MS (thioglycerol + Na+ matrix)
m/e ([M + 4Na - 3H]+) 757.0571 (100%); calcd 757.0587.
3-O-Decanoyl-2-(decanoylamino)-6-O-[3-O-decanoyl-2-(deca-
noylamino)-2-deoxy-â-D-glucopyranosyl]-2-deoxy-r-D-gluco-
pyranose 1,4′-Bisphosphate (3). 1H NMR (CD3OD) δ 5.48-5.46 (m,
1H), 5.25 (t, J ) 9.8 Hz, 1H), 5.17 (t, J ) 9.8 Hz, 1H), 4.77 (d, J )
8.3 Hz, 1H), 4.22 (q, J ) 9.3 Hz, 1H), 4.14 (dt, J ) 10.7, 2.9 Hz, 1H),
4.07 (d, J ) 11.7 Hz, 1H), 4.02-3.99 (m, 1H), 3.92-3.79 (m, 4H),
3.60 (t, J ) 9.8 Hz, 1H), 3.51-3.50 (m, 1H), 2.33-2.31 (m, 4H), 2.21-
2.16 (m, 4H), 1.59-1.55 (m, 8H), 1.33-1.25 (m, 48H), 0.91-0.88
(m, 12H). 13C NMR (CD3OD) δ 176.80, 176.49, 175.28, 174.97, 102.77,
96.28 (d, J ) 5.3 Hz), 76.89, 74.63, 74.35, 73.94, 69.40, 69.19, 62.02,
55.58, 53.40 (d, J ) 8.4 Hz), 37.68, 37.23, 35.42, 35.20, 33.32, 33.27,
33.25, 30.94, 30.88, 30.84, 30.80, 30.78, 30.75, 30.69, 30.67, 30.64,
30.54, 27.24, 27.14, 26.24, 26.14, 23.97, 23.93, 14.66, 14.63. 31P NMR
(CD3OD) δ 3.88, 2.06. HRFAB-MS (thioglycerol + Na+ matrix) m/e
([M + 4Na - 3H]+) 1183.5773 (100%); calcd 1183.5776.
2-Deoxy-3-O-hexanoyl-2-(hexanoylamino)-2-r-D-glucopyranose
4-Phosphate (4). As described for 12, compound 8 (500 mg, 1.02
mmol) was treated with benzyl chloroformate (180 µL, 1.22 mmol)
and DMAP (124 mg, 1.02 mmol) to afford tert-butyldimethylsilyl 6-O-
(benzyloxycarbonyl)-2-deoxy-3-O-hexanoyl-2-(hexanoylamino)-â-D-
9
2434 J. AM. CHEM. SOC. VOL. 125, NO. 9, 2003