Page 11 of 16
The Journal of Organic Chemistry
thereafter by filtration. The product residue was collected 105.6, 101.4, 101.3, 100.7, 99.3, 78.0, 75.5, 74.6, 73.6, 73.1,
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in vacuo and dissolved again in dimethylformamide (DMF)
(20 mL), into which benzaldehyde dimethylacetal (mL, 23.1
mmol) and camphorsulfonic acid (430 mg, 1.85 mmol) were
added and the reaction was allowed to proceed at 50 °C
overnight. The reaction was quenched with Et3N, diluted
with DCM (100 mL) and washed with a saturated water so-
lution of NaHCO3 followed by saturated brine, and then
dried over Na2SO4, filtered, and concentrated in vacuo. Due
to limited solubility, the resulting residue was used in the
next step without purification.
72.5, 71.9, 71.5, 70.5, 68.4, 67.1, 65.9, 60.3, 20.9, 20.7, 20.6,
20.6. ESI HRMS: m/z calcd for C41H46NaO15 [M + Na]+
801.2729, found 801.2733.
Synthesis of benzyl 1-ol-2,3-di-O-acetyl-6-O-benzyl-
β–D–glucopyranosyl-(1→4)-2,3-di-O-acetyl-6-O-ben-
zyl-β-D-glucopyranoside (T7). Triethylsilane (0.835 g, 7.2
mmol) and trifluoromethanesulfonic acid (TfOH, 1.08 g, 7.2
mmol) were sequentially added into a cooled (-78 °C) solution
of T6 (1.8 g, 2.4 mmol) in anhydrous DCM. The reaction mix-
ture was stirred at -78 °C for 1 h and then quenched with meth-
anol and triethyl amine. The resulting mixture was washed with
saturated aqueous NaHCO3 and water, and dried over Na2SO4.
The filtrate was concentrated in vacuo and the resulting residue
was purified by silica gel column chromatography (hex-
ane:ethyl acetate:dichloromethane = 3:1:1) to afford com-
pound T7 (1.68 g, 90%) as colorless syrup. 1H NMR (800 MHz,
Chloroform-d) δ 7.46 – 7.22 (m, 15H), 5.10 (t, J = 9.4 Hz, 1H),
5.03 (dd, J = 9.8, 7.9 Hz, 1H), 4.94 – 4.88 (m, 2H), 4.77 (dd, J
= 11.1, 6.0 Hz, 2H), 4.63 (d, J = 12.4 Hz, 1H), 4.53 (t, J = 11.9
Hz, 3H), 4.50 (d, J = 8.0 Hz, 1H), 4.47 (d, J = 8.0 Hz, 1H), 3.96
(t, J = 9.5 Hz, 1H), 3.80 – 3.74 (m, 2H), 3.72 (td, J = 10.3, 9.7,
3.8 Hz, 2H), 3.43 (dt, J = 10.0, 2.5 Hz, 1H), 3.32 (dt, J = 9.2,
4.4 Hz, 1H), 3.10 (d, J = 3.7 Hz, 1H), 2.06 (s, 3H), 2.01 (s, 3H),
1.96 (s, 3H), 1.96 (s, 3H). 13C{1H} NMR (201 MHz, Chloro-
form-d) δ 171.2, 170.2, 169.7, 169.1, 137.7, 137.4, 137.0,
128.6, 128.6, 128.4, 128.1, 128.1, 128.0, 127.9, 127.7, 100.1,
75.8, 75.0, 74.8, 73.7, 73.6, 72.8, 71.8, 71.6, 70.7, 70.2, 69.8,
67.3, 20.9, 20.7, 20.7, 20.7. ESI HRMS: m/z calcd for
C41H48NaO15 [M + Na]+ 803.2885, found 803.2876.
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Synthesis of phenyl 2,3-di-O-acetyl-4,6-O-benzyli-
dene-1-thio-β–D–glucopyranoside (T4). The crude diol
T3 from the previous synthesis was dissolved in anhydrous
pyridine (10 mL) into which acetic anhydride (10 mL) was
added. The reaction was stirred overnight at room temper-
ature and quenched with methanol. Solvent was removed at
reduced pressure and the residue was washed with 4M
aqueous HCl, saturated aqueous NaHCO3, and brine, and
dried over anhydrous Na2SO4. The residue was purified by
silica gel column chromatography (hexane:ethyl acetate =
4:1) to afford T4 (5.1 g, 74% three steps) as a white foam.
1H NMR (800 MHz, Chloroform-d) δ 7.51 – 7.46 (m, 2H), 7.44
– 7.40 (m, 2H), 7.35 (ddd, J = 8.1, 6.3, 3.7 Hz, 6H), 5.50 (s,
1H), 5.34 (t, J = 9.3 Hz, 1H), 5.01 (dd, J = 10.1, 8.9 Hz, 1H),
4.81 (d, J = 10.0 Hz, 1H), 4.39 (dd, J = 10.6, 5.0 Hz, 1H), 3.79
(t, J = 10.3 Hz, 1H), 3.67 (t, J = 9.6 Hz, 1H), 3.58 (td, J = 9.7,
5.0 Hz, 1H), 2.10 (s, 3H), 2.03 (s, 3H). 13C{1H} NMR (201
MHz, Chloroform-d) δ 170.1, 169.5, 136.7, 133.0, 131.7,
129.2, 129.1, 128.4, 128.3, 126.2, 101.5, 86.6, 78.1, 77.2,
77.1, 76.9, 72.9, 70.8, 70.7, 68.5, 20.8, 20.8. The NMR spec-
tral data are in accordance with literature.39 ESI HRMS: m/z
calcd for C23H24NaO7S [M + Na]+ 467.1135, found 467.1131.
Synthesis of benzyl 2,3,4,6-tetra-O-acetyl-β-D-[1-
13C]glucopyranosyl-(1→4)-1-2,3-di-O-acetyl-6-O-ben-
zyl-β–D–glucopyranosyl-(1→4)-2,3-di-O-acetyl-6-O-
benzyl-β-D-glucopyranoside (T8). A mixture of glycosyl
acceptor T7 (1.68 g, 2.16 mmol) and donor peracetyl-gluco-
pyranosyl-trichloroacetimidate (1.169 g, 2.376 mmol) was
stirred in 20 mL anhydrous diethyl ether/dichloromethane
(1:1) with molecular sieves (4Å) at room temperature un-
der argon for 30 min. The mixture was then cooled to –20
°C and trimethylsilyl trifluoromethanesulfonate (TMSOTf,
12 μL, 0.068 mmol) was added into it. The reaction was
slowly warmed to room temperature over 1 h. TLC analysis
showed complete conversion of starting material to a major
product. The reaction was quenched by the addition of 0.1
mL triethylamine and filtered. The filtrate was concentrated
in vacuum and purified by silica gel chromatography (hex-
ane: ethyl acetate = 4:1) to yield protected trisaccharide T8
(1.56 g, 65%) as colorless syrup. 1H NMR (800 MHz, Chlo-
roform-d) δ 7.45 – 7.30 (m, 15H), 5.08 (t, J = 9.5 Hz, 1H), 5.03
– 4.98 (m, 1H), 4.93 (q, J = 9.7, 9.3 Hz, 2H), 4.88 (d, J = 12.3
Hz, 1H), 4.80 (q, J = 8.3, 7.6 Hz, 1H), 4.75 – 4.72 (m, 1H), 4.65
(d, J = 11.7 Hz, 1H), 4.60 (d, J = 12.4 Hz, 1H), 4.54 – 4.44 (m,
3H), 4.39 – 4.34 (m, 1H), 4.36 – 4.29 (m, 1H), 4.28 (dt, J =
16.6, 8.4 Hz, 1H), 4.10 (q, J = 7.2 Hz, 1H), 3.99 – 3.89 (m, 2H),
3.90 – 3.81 (m, 1H), 3.74 (d, J = 2.5 Hz, 1H), 3.72 – 3.66 (m,
1H), 3.65 (dt, J = 10.8, 3.3 Hz, 1H), 3.41 (dt, J = 9.9, 2.6 Hz,
1H), 3.30 (d, J = 9.4 Hz, 1H), 3.26 – 3.21 (m, 1H), 3.10 – 3.05
(m, 1H), 2.06 (s, 3H), 2.01 (s, 3H), 2.00 (s, 3H), 1.98 (s, 4H),
1.97 (s, 3H), 1.96 (s, 3H), 1.96 (s, 3H), 1.93 (s, 3H). 13C{1H}
NMR (201 MHz, Chloroform-d) δ 170.5, 170.3, 170.2, 170.1,
169.6, 169.3, 169.0, 168.7, 137.6, 137.1, 137.0, 128.8, 128.7,
128.6, 128.4, 128.4, 128.3, 128.2, 128.2, 128.1, 127.9, 127.6,
Synthesis of benzyl 2,3-di-O-acetyl-4,6-O-benzyli-
dene-β–D–glucopyranosyl-(1→4)-2,3-di-O-acetyl-6-O-
benzyl-β-D-glucopyranoside (T6). A solution of glycosyl
donor T4 (1.5 g, 3.4 mmol) and acceptor T5 (synthesized
according to literature40) (1.8 g, 4.8 mmol) in anhydrous
DCM (10 mL) was stirred with activated molecular sieves (4
Å) under argon for 30 min. N-iodosuccinimide (0.765 g, 3.4
mmol) was then added and stirring was continued for 30
min more. After addition of a catalytic amount of silver tri-
flate (AgOTf, 0.009 g, 0.034 mmol), the color of the reaction
mixture turned yellow brown. The reaction was quenched
by addition of triethyl amine (Et3N) and stirred for an addi-
tional 20 min. This reaction mixture was diluted with DCM
and washed with sodium thiosulfate to remove iodine. The re-
sulting residue was collected in vacuo and purified by silica gel
column chromatography (hexane:ethyl acetate = 3:1) to afford
1
T6 (1.8 g, 70%) as colorless syrup. H NMR (800 MHz, Chlo-
roform-d) δ 7.47 – 7.41 (m, 6H), 7.39 – 7.34 (m, 7H), 7.32 –
7.30 (m, 2H), 5.47 (s, 1H), 5.19 (t, J = 9.5 Hz, 1H), 5.14 (t, J =
9.4 Hz, 1H), 5.03 (dd, J = 9.7, 8.0 Hz, 1H), 4.91 (d, J = 12.3 Hz,
1H), 4.88 (dd, J = 9.3, 8.0 Hz, 1H), 4.80 (d, J = 12.0 Hz, 1H),
4.64 (d, J = 12.3 Hz, 1H), 4.60 – 4.50 (m, 2H), 4.35 (dd, J =
10.4, 5.0 Hz, 1H), 4.13 (q, J = 7.2 Hz, 1H), 4.00 (t, J = 9.5 Hz,
1H), 3.78 (qd, J = 11.1, 2.8 Hz, 2H), 3.70 (t, J = 10.2 Hz, 1H),
3.61 (t, J = 9.6 Hz, 1H), 3.45 (ddd, J = 9.9, 3.4, 1.9 Hz, 1H),
3.32 (td, J = 9.7, 5.0 Hz, 1H), 2.03 (s, 3H), 2.02 (s, 3H), 2.02
(s, 3H), 1.99 (s, 3H). 13C{1H} NMR (201 MHz, Chloroform-d)
δ 170.0, 169.6, 169.5, 169.0, 137.6, 136.9, 136.7, 129.1,
128.6, 128.3, 128.2, 128.2, 128.1, 128.0, 127.8, 127.6, 126.1,
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