H.-Y.L. Wang et al. / Tetrahedron 69 (2013) 3432e3436
3435
4.3. (2R,3S,4S,5S,6R)-2-(((2R,3R,4aS,5S,7R,8R,8aR)-7-(Benzy-
loxy)-2,3-dimethoxy-2,3,5-trimethylhexahydro-2H-pyrano-
[3,4-b]-[1,4]dioxin-8-yl)oxy)-6-methyltetrahydro-2H-pyran-
3,4,5-triol (16)
J¼3.6,1.8 Hz,1H), 3.81 (dd, J¼9.6, 3.6 Hz,1H), 3.80 (dq, J¼9.6, 6.0 Hz,
1H), 3.75 (dd, J¼9.6, 3.6 Hz, 1H), 3.38 (dd, J¼9.6, 9.6 Hz, 1H), 3.32
(dd, J¼9.0, 9.0 Hz, 1H), 1.25 (d, J¼6.0 Hz, 3H), 1.24 (d, J¼6.0 Hz, 3H);
13C NMR (150 MHz, CD3OD)
d 100.1, 92.7, 77.8, 74.6, 74.2, 72.6, 72.3,
71.4, 70.3, 69.8, 18.4, 18.1; HRMS (CI): calcd for [C12H22O9Naþ]:
333.11560, found: 333.11566.
To a solution of allylic alcohol 15 (30 mg, 0.063 mmol) in tert-
butanol/acetone (125
lution of N-methylmorpholine-N-oxide/water (50% w/v, 65
m
L, 1:1 (v/v), 0.5 M) at 0 ꢀC was added a so-
m
L,1 M).
4.6. (3R,4R,5R,6S)-6-Methyl-3-(((2S,3R,4R,5R,6S)-3,4,5-
trihydroxy-6-methyltetrahydro-2H-pyran-2-yl)oxy)-tetrahy-
dro-2H-pyran-2,4,5-triol (3)
Crystalline OsO4 (0.16 mg, 1 mol %) was added and the reaction
mixture was stirred for 12 h at 0 ꢀC. The reaction mixture was then
quenched with 500
mL of saturated Na2S2O3 solution, extracted
with EtOAc (5ꢁ2 mL), and dried over with Na2SO4 and concen-
trated under reduced pressure. The compound was purified by flash
chromatography eluting with 85% EtOAc in hexanes to give the title
compound 16 (29.9 mg, 0.058 mmol, 93%); colorless oil; Rf 0.56
To a solution of di-saccharide 6 (26 mg, 0.05 mmol) in CH2Cl2
(0.5 mL), was added the 0.1 mL of 10:1 TFA/H2O. The reaction
mixture was stirred at room temperature for 40 min. The reaction
mixture was quenched with saturated 5 mL NaHCO3 solution, dried
over with Na2SO4, and concentrated to remove water and solvent
under reduced pressure. The crude compound was purified by
passing through a pad of silica gel eluting with 10% MeOH in EtOAc
to give the benzyl di-saccharide 17; To a solution of the benzyl di-
saccharide 17 in 0.5 mL MeOH was added 10% Pd/C (100 mg). The
reaction suspension was degassed and replaced atmosphere with
hydrogen gas three times. The reaction suspension was stirred with
hydrogen balloon for 24 h, filtered by passing through a pad of
Celite, concentrated under reduced pressure and under vacuo to
give the title compound 3 (13 mg, 0.043 mmol, 85%); viscous oil; Rf
(10% MeOH in EtOAc); [
a]
25 ꢂ50 (c 1.0, CH2Cl2); IR (thin film, cmꢂ1
)
D
3304, 2938, 2775, 2100, 1128, 1050; 1H NMR (600 MHz, CDCl3)
d
7.35e7.25 (m, 5H), 4.75 (d, J¼0.6 Hz, 1H), 4.74 (d, J¼1.2 Hz, 1H),
4.67 (d, J¼12.0 Hz, 1H), 4.47 (d, J¼12.0 Hz, 1H), 4.26 (dq, J¼9.6,
6.0 Hz, 1H), 3.99 (dd, J¼10.2, 3.0 Hz, 1H), 3.96 (m, 1H), 3.95 (dd,
J¼3.6, 1.8 Hz, 1H), 3.81 (dq, J¼9.6, 6.0 Hz, 1H), 3.64 (dd, J¼10.2,
10.2 Hz, 1H), 3.40 (dd, J¼9.6, 9.6 Hz, 1H), 3.23 (s, 3H), 3.22 (s, 3H),
1.25 (s, 3H), 1.24 (d, J¼6.0 Hz, 3H), 1.24 (s, 3H), 1.24 (d, J¼6.0 Hz, 3H);
13C NMR (150 MHz, CDCl3)
d 137.4,128.7 (2C),128.2 (2C),128.1, 99.9,
99.7, 98.5, 97.7, 74.00, 73.95, 72.2, 71.3, 69.4, 68.8, 68.0, 67.5, 67.1,
48.2, 47.9, 18.0, 17.9, 17.5, 16.9; HRMS (CI): calcd for [C25H38O11Naþ]:
537.23063, found: 537.23074.
0.31 (20% methanol in EtOAc); [
a
]
25 ꢂ20 (c 1.0, MeOH); IR (thin film,
D
cmꢂ1) 3351, 2981, 2935, 1645, 1055, 1032; 1H NMR (600 MHz,
CD3OD)
d
5.20 (d, J¼1.8 Hz, 1H), 4.98 (d, J¼1.8 Hz, 1H), 3.89 (dd,
4.4. (2R,3S,4S,5S,6R)-2-(((2R,3R,4R,5R,6S)-2-(Benzyloxy)-4,5-
dihydroxy-6-methyltetrahydro-2H-pyran-3-yl)oxy)-6-
methyltetrahydro-2H-pyran-3,4,5-triol (18)
J¼9.6, 3.6 Hz,1H), 3.85 (dq, J¼9.6, 6.0 Hz,1H), 3.84 (dd, J¼3.6,1.8 Hz,
2H), 3.78 (dq, J¼9.6, 6.0 Hz, 1H), 3.75 (dd, J¼9.6, 3.6 Hz, 1H), 3.44
(dd, J¼9.6, 9.6 Hz, 1H), 3.39 (dd, J¼9.6, 9.6 Hz, 1H), 1.31 (d, J¼6.0 Hz,
3H), 1.29 (d, J¼6.0 Hz, 3H); 13C NMR (150 MHz, CD3OD)
d 104.2,
To a solution of di-saccharide 16 (19.3 mg, 0.0375 mmol) in
CH2Cl2 (375 mL) was added 75 mL of TFA/H2O (10:1). The reaction
94.6, 81.2, 74.7, 74.1, 72.4, 72.2, 71.9, 70.3, 69.5,18.4,18.0; HRMS (CI):
calcd for [C12H22O9Naþ]: 333.11560, found: 333.11568.
mixture was stirred at room temperature for 4 h. The reaction
mixture was then quenched with saturated NaHCO3 solution
(3.0 mL), dried over with Na2SO4 and concentrated under reduced
pressure. The crude product was purified by flash chromatography
eluting with 8% MeOH in EtOAc to give the title compound 18
4.7. (3R,4R,5R,6S)-3-(((2S,3R,4R,5S,6S)-3,5-Dihydroxy-6-
methyl-4-(((2S,3R,4R,5R,6S)-3,4,5-trihydroxy-6-
methyltetrahydro-2H-pyran-2-yl)oxy)-tetrahydro-2H-pyran-
2-yl)oxy)-6-methyltetrahydro-2H-pyran-2,4,5-triol (2)
(14.7 mg, 0.0367 mmol, 98%); colorless oil; Rf 0.48 (20% MeOH in
25
EtOAc); [
a
]
þ5.0 (c 1.0, MeOH); IR (thin film, cmꢂ1) 3372, 2071,
To a solution of tri-saccharide 5 (42 mg, 0.05 mmol) in CH2Cl2
(0.5 mL) was added 0.1 mL of 10:1 TFA/H2O. The reaction mixture
was stirred at room temperature for 40 min. The reaction mixture
was quenched with saturated 5 mL of NaHCO3 solution, dried over
with Na2SO4, and concentrated to remove water and solvent under
reduced pressure. The crude compound was purified by passing
through a pad of silica gel eluting with 10% MeOH in EtOAc to give
diacetate; to the solution of the subsequent diacetate in MeOH
(0.2 mL) was added LiOH (9.6 mg, 0.4 mmol) and stirred for 5 h. The
reaction mixture was concentrated under reduced pressure and
purified by passing through a pad of silica gel eluting with 15%
MeOH in EtOAc to give the benzyl tri-saccharide 19; the resulting
benzyl tri-saccharide 19 was dissolved in 0.5 mL MeOH and added
10% Pd/C (100 mg). The reaction suspension was degassed and
replaced atmosphere with hydrogen gas for three times. The re-
action suspension was stirred under the hydrogen balloon for 24 h,
filtered by passing through a pad of Celite, concentrated under
reduced pressure and under vacuo to give the title compound 2
D
1508, 1334, 1120, 973, 786; 1H NMR (600 MHz, CD3OD)
d 7.35e7.28
(m, 5H), 4.87 (d, J¼1.8 Hz, 1H), 4.74 (d, J¼1.8 Hz, 1H), 4.70 (d,
J¼12.0 Hz, 1H), 4.54 (d, J¼12.0 Hz, 1H), 3.98 (dq, J¼9.6, 6.0 Hz, 1H),
3.92 (dd, J¼3.6, 1.8 Hz, 1H), 3.81 (dd, J¼3.6, 1.8 Hz, 1H), 3.79 (dd,
J¼9.6, 3.6 Hz, 1H), 3.74 (dd, J¼9.6, 3.0 Hz, 1H), 3.62 (dq, J¼9.0,
6.0 Hz, 1H), 3.37 (dd, J¼9.6, 9.6 Hz, 1H), 3.35 (dd, J¼9.6, 9.6 Hz, 1H),
1.25 (d, J¼6.6 Hz, 3H), 1.24 (d, J¼6.6 Hz, 3H); 13C NMR (150 MHz,
CD3OD)
d 139.1, 129.6 (2C), 129.2 (2C), 129.0, 100.1, 97.9, 76.9, 74.3,
74.1, 72.6, 72.3, 71.7, 70.5, 70.4, 70.3, 18.2, 18.0; HRMS(CI): calcd for
[C19H28O9þNaþ]: 423.16255, found: 423.16269.
4.5. (3R,4R,5R,6S)-6-Methyl-3-(((2R,3S,4S,5S,6R)-3,4,5-
trihydroxy-6-methyltetrahydro-2H-pyran-2-yl)oxy)-tetrahy-
dro-2H-pyran-2,4,5-triol (4)
To a solution of benzyl di-saccharide 18 (11.4 mg, 0.030 mmol) in
MeOH (0.1 mL) was added 10% Pd/C (60 mg). The reaction sus-
pension was degassed and replaced atmosphere with hydrogen gas
three times. The reaction mixture was stirred for 24 h and filtered
through a pad of Celite. The solute was concentrated under reduced
pressure to give the title compound 4 (8.2 mg, 0.026 mmol, 90%);
(18.5 mg, 0.041 mmol, 81%); viscous oil; Rf 0.19 (20% MeOH in
25
EtOAc); [
a
]
D
ꢂ82 (c 1.2, MeOH); IR (thin film, cmꢂ1) 3356, 2981,
2934, 1572, 1416, 1059, 986; 1H NMR (600 MHz, CD3OD)
d 5.18 (d,
J¼1.8 Hz, 1H), 5.10 (d, J¼1.8 Hz, 1H), 4.98 (d, J¼1.8 Hz, 1H), 4.12 (dd,
J¼3.6, 1.8 Hz, 1H), 4.03 (dd, J¼3.6, 1.8 Hz, 1H), 3.86 (m, 7H), 3.57 (dd,
J¼9.6, 9.6 Hz, 1H), 3.45 (dd, J¼9.6, 9.6 Hz, 1H), 3.43 (dd, J¼9.6,
9.6 Hz, 1H), 1.35 (d, J¼6.0 Hz, 3H), 1.31 (d, J¼6.0 Hz, 3H), 1.29 (d,
viscous oil; Rf 0.52 (40% MeOH in EtOAc); [
a]
25 þ16 (c 1.0, MeOH); IR
D
(thin film, cmꢂ1) 3375, 2991, 2942, 1570, 1145, 995; 1H NMR
(600 MHz, CD3OD)
3.98 (dq, J¼9.6, 6.0 Hz, 1H), 3.86 (dd, J¼3.0, 1.8 Hz, 1H), 3.83 (dd,
d
5.10 (d, J¼1.8 Hz, 1H), 4.79 (d, J¼1.2 Hz, 1H),
J¼6.0 Hz, 3H); 13C NMR (150 MHz, CD3OD)
d 104.0(2C), 94.7, 80.9,