Crich et al.
3H), 4.48 (d, J ) 12.5 Hz, 1H), 4.41(dd, J ) 3.0, 10.0 Hz, 1H),
4.24-4.36 (m, 5H), 4.18 (t, J ) 9.5 Hz, 1H), 4.07-4.08 (m, 1H),
3.95 (d, J ) 3.0 Hz, 1H), 3.91 (t, J ) 10.0 Hz, 2H), 3.77 (dd, J )
3.5, 10.0 Hz, 1H), 3.12 (dt, J ) 4.5, 9.5 Hz, 1H); 13C NMR (125
MHz, CDCl3) δ 138.8, 137.6, 137.5, 137.1, 133.8, 133.4, 133.2,
131.8, 130.7, 129.3, 129.1, 129.0, 128.9, 128.61, 128.55, 128.4,
128.2, 128.1, 127.9, 127.3, 127.0, 126.5, 126.3, 126.2, 126.1, 125.2,
120.3, 101.9, 101.5, 98.4, 90.5, 86.0, 84.5, 78.4, 77.4, 76.6, 75.7,
75.0, 72.7, 72.1, 68.64, 68.56, 67.7, 65.5, 58.8; ESIHRMS calcd
for C59H54O10SNa [M + Na]+ 977.3336, found 977.3380.
Phenyl 4,6-O-Benzylidene-2-O-benzyl-â-D-mannopyranosyl-
(1f3)-4,6-O-benzylidene-2-O-benzyl-1-thio-R-D-mannopyrano-
side (32). Removal of the naphthylpropargyl group from compound
31 (1.30 g, 1.36 mmol) by the standard protocol gave product 32
(0.95 g, 1.20 mmol) in 88% yield: [R]25D -2.2 (c 1.0, CHCl3); 1H
NMR (500 MHz, CDCl3) δ 7.45-7.49 (m, 6H), 7.24-7.38 (m,
19H), 5.68 (s, 1H), 5.64 (s, 1H), 5.33 (s, 1H), 5.06 (d, J ) 11.0
Hz, 1H), 4.77 (d, J ) 12.0 Hz, 1H), 4.62 (d, J ) 12.0 Hz, 1H),
4.55 (d, J ) 12.0 Hz, 1H), 4.42 (dd, J ) 3.0, 10.0 Hz, 1H), 4.35-
4.40 (m, 2H), 4.22-4.30 (m, 3H), 4.12-4.13 (m, 1H), 3.92 (t, J )
10.0 Hz, 1H), 3.83 (t, J ) 9.0 Hz, 1H), 3.74-3.78 (m, 2H), 3.58-
3.66 (m, 1H), 3.10 (dt, J ) 4.5, 9.5 Hz, 1H), 2.53 (d, J ) 9.5 Hz,
1H); 13C NMR (125 MHz, CDCl3) δ 138.1, 137.44, 137.36, 137.1,
133.7, 131.8, 129.3, 129.08, 129.05, 128.7, 128.6, 128.5, 128.4,
128.2, 127.9, 127.8, 126.3, 102.0, 101.8, 97.8, 86.1, 79.8, 77.5,
77.30, 77.25, 75.4, 74.9, 72.4, 72.2, 70.2, 68.7, 68.6, 67.0, 65.6;
ESIHRMS calcd for C46H46O10SNa [M + Na]+ 813.2704, found
813.2694.
J ) 5.0, 10.0 Hz, 1H); 13C NMR (125 MHz, CDCl3) δ 141.6, 138.8,
138.3, 137.5, 137.1, 136.6, 133.4, 133.2, 131.9, 130.7, 129.6, 129.2,
129.0, 128.9, 128.7, 128.5, 128.3, 128.23, 128.19, 128.1, 127.8,
127.4, 127.0, 126.5, 126.3, 126.2, 125.2, 124.4, 120.3, 101.9, 101.7,
101.5, 98.4, 97.9, 96.3, 90.4, 84.4, 78.4, 77.3, 77.0, 76.4, 76.1, 74.9,
74.3, 73.9, 73.7, 72.7, 72.1, 70.7, 70.2, 68.6, 68.2, 67.8, 58.6;
ESIHRMS calcd for C79H74O16SNa [M + Na]+ 1333.4590, found
1333.4589.
Methyl 4,6-O-Benzylidene-2-O-benzyl-3-O-[3-(naphthalen-1-
yl)prop-2-ynyl]-â-D-mannopyranosyl-(1f3)-4,6-O-benzylidene-
2-O-benzyl-â-D-mannopyranosyl-(1f3)-4,6-O-benzylidene-2-O-
benzyl-R-D-mannopyranosyl-(1f3)-4,6-O-benzylidene-2-O-benzyl-
â-D-mannopyranosyl-(1f3)-4,6-O-benzylidene-2-O-benzyl-â-D-
mannopyranosyl-(1f3)-4,6-O-benzylidene-2-O-benzyl-â-D-
mannopyranosyl-(1f3)-4,6-O-benzylidene-2-O-benzyl-â-D-
mannopyranoside (35R) and Methyl 4,6-O-Benzylidene-2-O-
benzyl-3-O-[3-(naphthalen-1-yl)-prop-2-ynyl]-â-D-
mannopyranosyl-(1f3)-4,6-O-benzylidene-2-O-benzyl-â-D-
mannopyranosyl-(1f3)-4,6-O-benzylidene-2-O-benzyl-â-D-
mannopyranosyl-(1f3)-4,6-O-benzylidene-2-O-benzyl-â-D-
mannopyranosyl-(1f3)-4,6-O-benzylidene-2-O-benzyl-â-D-
mannopyranosyl-(1f3)-4,6-O-benzylidene-2-O-benzyl-â-D-
mannopyranosyl-(1f3)-4,6-O-benzylidene-2-O-benzyl-â-D-
mannopyranoside (35â). To a stirred solution of sulfoxide donor
34 (120 mg, 0.09 mmol), TTBP (40 mg, 0.16 mmol), and 4 Å
molecular sieves in a mixed solvent of CH2Cl2 and 1-octene (7.5
mL, v/v, 4:1), at -78 °C under argon atmosphere, was added Tf2O
(15 µL, 0.09 mmol). After the reaction mixture was stirred at -78
°C for 30 min, a solution of acceptor 29 (80 mg, 0.075 mmol) in
CH2Cl2 (1.5 mL) was added. The stirring was maintained for
30 min at -78 °C, and the reaction temperature was allowed to
warm to -20 °C slowly over 30 min. The resultant mixture
was stirred for another 30 min at -20 °C before it was quenched
by pouring into aq NaHCO3 solution. The mixture was diluted
with CH2Cl2 and filtered through Celite. The organic layer was
washed with brine, dried over Na2SO4, and concentrated. The
residue was purified by chromatography on silica gel (hexane/ethyl
acetate; 2:1f 1.5:1) to give a mixture of hexasaccharides 35R,
35â (103 mg, 61%) in 1:1 ratio as estimated by 1H NMR
spectroscopy of the mixture. Separation of 30 mg of the mixture
by RP HPLC using a gradient of 90% A to 100% A over 144 min
(A: CH3CN, B: H2O; Varian Microsorb C18 250 × 21.4 mm;
flow rate: 5 mL/min; UV detection: 215 nm) gave pure samples
Phenyl 4,6-O-Benzylidene-2-O-benzyl-3-O-[3-(naphthalen-1-
yl)-prop-2-ynyl]-â-D-mannopyranosyl-(1f3)-4,6-O-benzylidene-
2-O-benzyl-â-D-mannopyranosyl-(1f3)-4,6-O-benzylidene-2-O-
benzyl-1-thio-R-D-mannopyranoside (33). Coupling of sulfoxide
donor 23 (0.063 g, 0.10 mmol) with thioglycoside 32 (0.062 g,
0.08 mmol) by the standard coupling protocol gave trisaccharide
33 (0.074 g, 0.06 mmol) as a colorless syrup in 73% yield: [R]27
D
-40.5 (c 1.0, CHCl3); 1H NMR (500 MHz, CDCl3) δ 8.33 (d, J )
8.0 Hz, 1H), 7.84 (t, J ) 7.5 Hz, 2H), 7.63 (d, J ) 7.0 Hz, 1H),
7.44-7.52 (m, 10H), 7.28-7.40 (m, 20H), 7.18-7.23 (m, 5H),
7.11-7.12 (m, 3H), 5.66 (s, 1H), 5.60 (s, 1H), 5.56 (s, 1H), 5.49
(s, 1H), 4.99 (d, J ) 12.0 Hz, 1H), 4.93 (d, J ) 12.0 Hz, 1H), 4.77
(t, J ) 12.0 Hz, 2H), 4.53-4.70 (m, 4H), 4.43 (dd, J ) 3.0, 10.0
Hz, 1H), 4.06-4.35 (m, 10H), 3.85-3.94 (m, 6H), 3.71 (dd, J )
3.0, 10.0 Hz, 1H), 3.08-3.14 (m, 2H); 13C NMR (125 MHz, CDCl3)
δ 138.8, 138.2, 137.5, 137.4, 137.0, 133.7, 133.4, 133.2, 131.9,
130.7, 129.3, 129.0, 128.9, 128.7, 128.5, 128.4, 128.3, 128.2, 128.1,
127.9, 127.8, 127.3, 126.9, 126.5, 126.3, 126.2, 125.2, 120.3, 101.8,
101.7, 101.5, 98.0, 90.4, 85.8, 84.4, 78.4, 76.1, 75.4, 74.9, 74.2,
73.9, 73.4, 72.3, 71.9, 68.6, 67.8, 65.5, 58.7; ESIHRMS calcd for
C79H74O15SNa [M + Na]+ 1317.4641, found 1317.4630.
of 35R, 35â.
1
Hexasaccharide 35R: [R]20 -127.7 (c 0.5, CHCl3); H NMR
D
(500 MHz, CDCl3) δ 8.33 (d, J ) 8.5 Hz, 1H), 7.82 (t, J ) 8.0
Hz, 2H), 7.62 (d, J ) 7.0 Hz, 1H), 7.05-7.50 (m, 61H), 6.97 (d,
J ) 7.5 Hz, 2H), 5.63 (s, 1H), 5.57 (s, 1H), 5.56 (s, 1H), 5.55 (s,
1H), 5.45 (s, 1H), 5.39 (s, 1H), 4.45-5.07 (m, 15H), 4.39 (dd, J )
3.5, 9.0 Hz, 2H), 3.68-4.25 (m, 33H), 3.63 (s, 3H), 3.60-3.65
(m, 1H), 3.45 (dt, J ) 4.5, 9.0 Hz, 1H), 3.05-3.12 (m, 3H), 3.01
(dt, J ) 4.5, 9.5 Hz, 1H); 13C NMR (125 MHz, CDCl3) δ 138.8,
138.29, 138.27, 138.2, 137.9, 137.7, 137.5, 137.4, 137.3, 133.4,
133.2, 130.7, 129.5, 129.00, 128.96, 128.91, 128.85, 128.7, 128.6,
128.47, 128.45, 128.4, 128.34, 128.29, 128.24, 128.21, 128.16,
128.1, 128.0, 127.88, 127.85, 127.8, 127.3, 126.9, 126.5, 126.3,
126.2, 125.2, 120.3, 103.9, 102.2, 101.8, 101.69, 101.65, 101.5,
98.8, 98.5, 97.6, 97.3, 90.4, 84.4, 78.8, 78.3, 77.3, 76.9, 76.1, 76.0,
75.1, 74.8, 74.24, 74.16, 74.1, 73.9, 73.8, 73.7, 73.5, 73.3, 73.2,
72.6, 72.4, 72.1, 71.8, 68.7, 68.6, 67.8, 67.7, 67.5, 64.6, 58.6, 57.7;
ESIHRMS calcd for C134H132O31Na [M + Na]+ 2259.8645, found
Phenyl 4,6-O-Benzylidene-2-O-benzyl-3-O-[3-(naphthalen-1-
yl)-prop-2-ynyl]-â-D-mannopyranosyl-(1f3)-4,6-O-benzylidene-
2-O-benzyl-â-D-mannopyranosyl-(1f3)-4,6-O-benzylidene-2-O-
benzyl-1-thio-R-D-mannopyranoside S-Oxide (34). To a stirred
solution of 33 (0.98 g, 0.76 mmol) in CH2Cl2 (40 mL) was added
a solution of m-CPBA (77%, 0.17 g, 0.76 mmol) in CH2Cl2 (2
mL) dropwise at -78 °C. The resultant mixture was stirred for 1
h during which time the temperature was allowed to warm up to
-20 °C slowly. The reaction mixture was then quenched by pouring
into aq NaHCO3 solution and was diluted with CH2Cl2. The organic
layer was separated, washed with 1 M aq NaOH solution and brine,
dried over anhydrous Na2SO4, and concentrated. The residue was
purified by chromatography on silica gel (hexane/ethyl acetate;
1.5:1) to give the title compound 34 (0.98 g, 98%): [R]25D -103.9
2259.8513.
1
Hexasaccharide 35â: [R]20 -132.2 (c 0.5, CHCl3); H NMR
D
1
(c 1.0, CHCl3); H NMR (500 MHz, CDCl3) δ 8.34 (d, J ) 8.0
(500 MHz, CDCl3) δ 8.33 (d, J ) 8.0 Hz, 1H), 7.83 (t, J ) 7.5
Hz, 2H), 7.63 (d, J ) 7.0 Hz, 1H), 7.09-7.51 (m, 63H), 5.62 (s,
1H), 5.55 (s, 1H), 5.53 (s, 1H), 5.51 (s, 1H), 5.50 (s, 1H), 5.48 (s,
1H), 4.98-5.08 (m, 5H), 4.89 (d, J ) 12.0 Hz, 1H), 4.66-4.83
(m, 7H), 4.59-4.63 (m, 2H), 4.53-4.54 (m, 1H), 4.39 (dd, J )
4.5, 10.5 Hz, 2H), 3.78-4.24 (m, 30H), 3.68 (dd, J ) 3.0, 9.5 Hz,
Hz, 1H), 7.84 (t, J ) 8.0 Hz, 2H), 7.11-7.65 (m, 39H), 5.58 (s,
2H), 5.48 (s, 1H), 5.01 (d, J ) 12.0 Hz, 1H), 4.93 (d, J ) 12.0 Hz,
1H), 4.58-4.77 (m, 7H), 4.43-4.52 (m, 2H), 4.11-4.31 (m, 8H),
4.08 (t, J ) 9.5 Hz, 1H), 3.94 (t, J ) 10.0 Hz, 1H), 3.85-3.88 (m,
4H), 3.71-3.78 (m, 2H), 3.15 (dt, J ) 5.0, 10.0 Hz, 1H), 3.08 (dt,
6814 J. Org. Chem., Vol. 72, No. 18, 2007