854
S. Serna et al. / Tetrahedron: Asymmetry 20 (2009) 851–856
aminopropyl)-3-ethylcarbodiimide
hydrochloride
(166 mg,
concentrated to dryness and the crude product was purified by
0.87 mmol) and 4-dimethylaminopyridine (50 mg, 0.40 mmol)
were added at room temperature. The reaction mixture was stirred
until TLC (hexane/EtOAc; 4/1) showed complete conversion of the
starting material (2 h). The mixture was diluted with EtOAc
(100 mL) and washed with aqueous HCl (0.01 M), water, saturated
aqueous NaHCO3 and brine. The organic layer was dried over anhy-
drous MgSO4, filtered and concentrated. The crude product was
purified by flash chromatography (hexane/EtOAc, 9/1 to 1/3) to
give the title compound as a white solid (350 mg, 98%). Rf 0.39
medium pressure flash chromatography (hexane/EtOAc, 93/7 to
1/1) to give the title compound as a white solid (600 mg, 82%). Rf
0.41 (hexane/EtOAc, 4/1); ½a D20
ꢂ
¼ þ22:1 (c 0.95, CHCl3); 1H NMR
(500 mg, CDCl3) d 7.85–6.89 (m, 26H, Ar), 5.52 (s, 1H, OCHPh),
5.33 (d, J = 8.1, 1H, H-1), 5.12 (d, J = 11.9, 1H, CH2Nap), 4.98 (d,
J = 11.9, 1H, CH2Nap), 4.81 (d, J = 12.3, 1H, CH2Ph), 4.78–4.69 (m,
2H, CH2Ph, H-10), 4.62 (d, J = 12.2, 1H, CH2Ph), 4.47 (d, J = 12.3,
1H, CH2Ph), 4.41 (dd, J = 8.8, 10.7, 1H, H-3), 4.21–4.10 (m, 3H, H-
2, H-4, H-6a0), 4.05 (dd, J = 3.1, 11.5, 1H, H-6a), 3.79 (d, J = 10.3,
1H, H-6b), 3.70–3.51 (m, 5H, H-5, H-20, H-30, H-40, H-6b0), 3.31–
(hexane/EtOAc, 4/1);
½
a 2D0
ꢂ
¼ þ7:3 (c 0.76, CHCl3); 1H NMR
t
(500 mg, CDCl3) d 7.87–7.69 (m, 4H, Ar), 7.56–7.32 (m, 10H, Ar),
7.12 (d, J = 8.0, 2H, Ar), 5.59 (s, 1H, OCHPh), 5.05–4.96 (m, 2H, H-
2, CH2Nap), 4.86 (d, J = 12.2, 1H, CH2Nap), 4.62 (d, J = 10.1, 1H, H-
1), 4.38 (dd, J = 5.0, 10.5, 1H, H-6a), 3.85–3.71 (m, 3H, H-3, H-4,
H-6b), 3.48 (td, J = 5.0, 9.6, 1H, H-5), 2.67 (t, J = 6.7, 2H, CH2Lev),
2.60–2.46 (m, 2H, CH2Lev), 2.34 (s, 3H, CH3Tol), 2.13 (s, 3H,
CH3Lev). 13C NMR (126 mg, CDCl3) d 206.11, 171.20, 138.51,
137.12, 135.55, 133.48, 133.18, 132.96, 129.67, 129.05, 128.28,
128.17, 128.00, 127.90, 127.64, 126.81, 126.12, 126.02, 125.86,
101.28, 87.06, 81.26, 79.59, 74.36, 71.74, 70.48, 68.54, 37.75,
29.79, 28.02, 21.15. HRMS (ESI): m/z calcd for C36H36NaO7S:
635.2079 [M+Na]+; found 635.2131.
3.19 (m, 2H, H-50, OH), 0.68 (s, 9H, BuTBS), 0.05 (s, 3H, CH3TBS),
ꢀ0.10 (s, 3H, CH3TBS). 13C NMR (126 mg, CDCl3)
d 138.52,
137.72, 137.32, 135.91, 133.71, 133.28, 133.01, 131.61, 128.97,
128.41, 128.24, 128.15, 127.94, 127.79, 127.65, 127.36, 127.10,
126.72, 126.09, 126.01, 125.83, 123.12, 103.63, 101.26, 93.51,
81.27, 80.29, 78.95, 77.93, 75.43, 74.68, 74.56, 74.40, 73.57,
68.67, 68.37, 66.30, 57.98, 25.30, 17.52, ꢀ4.25, ꢀ5.52. HRMS
(ESI): m/z calcd for C58H63NNaO12Si: 1016.4017 [M+Na]+; found
1016.4034.
4.1.4. tert-Butyldimethylsilyl 2-O-acetyl-4,6-O-benzylidene-3-
O-(2-naphthylmethyl)-b-
D-mannopyranosyl-(l?4)-3,6-di-O-
benzyl-2-deoxy-2-phthalamido-b-
D-glucopyranoside 8
4.1.2. tert-Butyldimethylsilyl 4,6-O-benzylidene-2-O-
To a cooled (0 °C) solution of compound 7 (1.26 g, 1.27 mmol) in
dry CH2Cl2 (55 mL), pyridine (4.2 mL, 51.9 mmol) and trifluoro-
methanesulfonic anhydride (3.5 mL, 20.8 mmol) were added. The
reaction mixture was stirred at 0 °C until TLC (hexane/EtOAc; 4/
1) showed complete conversion of the starting material (1 h). The
mixture was diluted with CH2Cl2 and washed with saturated NaH-
CO3 solution. The organic layer was dried over anhydrous MgSO4,
filtered and concentrated to afford the trifluoromethanesulfonate,
which was used in the next step without further purification. The
crude product was dissolved in dry toluene (28 mL) and tetrabutyl-
ammonium acetate (1.04 g, 3.45 mmol) was added. The resulting
suspension was sonicated for 18 h. The reaction mixture was con-
centrated to dryness and the crude product was purified by flash
chromatography (hexane/EtOAc, 4/1) to give the title compound
as a white solid (960 mg, 73%, two steps). Rf 0.44 (hexane/EtOAc,
levulinoyl-3-O-(2-naphthylmethyl)-b-
D-glucopyranosyl-(l?4)-
3,6-di-O-benzyl-2-deoxy-2-phthalamido-b-
D
-glucopyranoside 6
A mixture of thioglycoside 4 (500 mg, 0.81 mmol), acceptor 538
(328 mg, 0.54 mmol) and 3 Å molecular sieves in dry CH2Cl2 (3 mL)
was stirred under argon for 45 min at room temperature. The mix-
ture was cooled to ꢀ20 °C and N-iodosuccinimide (200 mg,
0.81 mmol) was added, followed by trimethylsilyl trifluorometh-
anesulfonate (15 lL, 0.08 mmol). The reaction mixture was stirred
at ꢀ20 °C until TLC (hexane/EtOAc; 4/1) showed complete conver-
sion of acceptor (90 min). The reaction was quenched by adding
Et3N (250 lL), filtered through a plug of Celite and the filtrate
was concentrated. The crude product was purified by medium
pressure flash chromatography (hexane/EtOAc, 95/5 to 60/40) to
give the title compound as a white foam (450 mg, 85%). Rf 0.31
(hexane/EtOAc, 4/1);
½
a 2D0
ꢂ
¼ þ5:7 (c 0.5, CHCl3); 1H NMR
4/1); ½a 2D0
ꢂ
¼ þ3:0 (c 0.20, CHCl3); 1H NMR (500 mg, CDCl3) d
(500 mg, CDCl3) d 7.85–6.91 (m, 26H, Ar), 5.50 (s, 1H, OCHPh),
5.30 (d, J = 8.1, 1H, H-1), 5.07–4.95 (m, 2H, H-20, CH2Nap), 4.83
(d, J = 12.3, 1H, CH2Nap), 4.75 (m, 2H, CH2Ph), 4.63 (d, J = 8.0, 1H,
H-10), 4.49 (d, J = 12.2, 1H, CH2Ph), 4.44 (d, J = 12.4, 1H, CH2Ph),
4.31–4.19 (m, 2H, H-6a0, H-3), 4.13–3.98 (m, 2H, H-2, H-4), 3.82
(dd, J = 3.1, 11.1, 1H, H-6a), 3.73–3.60 (m, 3H, H-6b, H-30, H-40),
3.55 (d, J = 9.1, 1H, H-5), 3.49 (t, J = 10.3, 1H, H-6b0), 3.27 (td,
J = 4.9, 9.5, 1H, H-50), 2.75–2.55 (m, 2H, CH2Lev), 2.52–2.34 (m,
7.84–6.89 (m, 26H, Ar), 5.57 (s, 1H, OCHPh), 5.55 (d, J = 2.5, 1H,
H-20), 5.33 (d, J = 8.1, 1H, H-1), 4.91–4.79 (m, 2H, CH2Ar), 4.77–
4.68 (m, 3H, CH2Ar, H-10), 4.47 (d, J = 12.2, 2H, CH2Ar), 4.32 (t,
J = 9.7, 1H, H-3), 4.20 (dd, J = 4.7, 10.4, 1H, H-6a0), 4.17–4.09 (m,
2H, H-2, H-4), 3.94 (t, J = 9.5, 1H, H-40), 3.83 (dd, J = 2.2, 11.0, 1H,
H-6a), 3.71 (d, J = 11.0, 1H, H-6b), 3.66–3.54 (m, 3H, H-5, H-30, H-
6b0), 3.20 (td, J = 4.9, 9.6, 1H, H-50), 2.22 (s, 3H, CH3CO), 0.68 (s,
t
9H, BuTBS), 0.05 (s, 3H, CH3TBS), ꢀ0.09 (s, 3H, CH3TBS). 13C NMR
t
2H, CH2Lev), 2.12 (s, 3H, CH3Lev), 0.65 (s, 9H, Bu TBS), 0.03 (s,
(126 mg, CDCl3) d 170.30, 168.24, 167.56, 138.64, 137.86, 137.44,
135.26, 133.68, 133.27, 132.95, 131.58, 128.95, 128.43, 128.20,
128.09, 127.91, 127.78, 127.72, 127.60, 127.12, 126.18, 126.14,
3H, CH3TBS), -0.12 (s, 3H, CH3TBS). 13C NMR (126 mg, CDCl3) d
206.11, 171.22, 138.70, 138.09, 137.26, 135.80, 133.63, 133.24,
132.94, 131.64, 129.02, 128.43, 128.27, 127.97, 127.90, 127.87,
127.81, 127.75, 127.67, 127.00, 126.53, 126.07, 125.93, 125.86,
123.03, 101.25, 100.67, 93.32, 81.73, 78.56, 78.05, 76.40, 74.89,
74.31, 74.11, 73.72, 73.60, 68.65, 67.91, 65.92, 57.85, 37.68,
29.82, 27.81, 25.33, 17.54, ꢀ4.22, ꢀ5.50. HRMS (ESI): m/z calcd
for C63H69NNaO14Si: 1114.4385 [M+Na]+; found 1114.4362.
125.99, 125.81, 125.36, 123.14, 123.01, 101.55, 99.50 (C-10, JC1 –
0
H10
= 160.0 Hz), 93.43, 79.24, 77.86, 76.77, 75.72, 74.38, 74.34,
73.42, 71.46, 69.17, 68.56, 68.45, 66.95, 57.83, 25.30, 21.05,
17.52, ꢀ4.26, ꢀ5.52. HRMS (ESI): m/z calcd for C60H65NNaO13Si:
1058.4122 [M+Na]+; found 1058.4124.
4.1.5. 2-O-Acetyl-4,6-O-benzylidene-3-O-(2-naphthylmethyl)-b-
D-
4.1.3. tert-Butyldimethylsilyl 4,6-O-benzylidene-3-O-(2-
mannopyranosyl-(l?4)-3,6-di-O-benzyl-2-deoxy-2-phthalamido-
naphthylmethyl)-b-
deoxy-2-phthalamido-b-
To a stirred solution of compound 6 (800 mg, 0.74 mmol) in
CH2Cl2 (20 mL) was added solution of hydrazine acetate
D
-glucopyranosyl-(l?4)-3,6-di-O-benzyl-2-
b-
D
-glucopyranosyl N-phenyl trifluoroacetimidate 10
To a cooled (0 °C) stirred solution of compound 8 (200 mg,
D
-glucopyranoside 7
0.19 mmol) in THF (1 mL) were added TBAF (1 M in THF, 300
0.30 mmol) and acetic acid (18 L, 0.30 mmol). The reaction mix-
lL,
a
l
(102 mg, 1.10 mmol) in MeOH (2.0 mL). The mixture was stirred
at room temperature until TLC (hexane/EtOAc; 7/3) showed com-
plete conversion of the starting material (1 h). The mixture was
ture was stirred at 0 °C until TLC (hexane/EtOAc; 4/1) showed com-
plete conversion of the starting material (2 h). The reaction
mixture was diluted with EtOAc (100 mL) and washed with satu-