7036
L. Ji et al. / Tetrahedron 69 (2013) 7031e7037
3.86 (d, J¼12.2 Hz, 1H, ABq), 3.48 (d, J¼4.9 Hz, 1H), 2.10 (s, 3H), 2.08
with brine (2ꢂ30 mL), dried over anhydrous Na2SO4, filtered, con-
centrated under reduced pressure to afford crude 15 as white crys-
talline solid. Colorless needle-shaped crystal (2.50 g, 94%) was
(s, 3H), 2.03 (s, 3H), 1.99 (s, 3H), 1.96 (s, 3H) ppm. 13C NMR
(101 MHz, CDCl3)
d
¼170.98, 170.70, 170.54, 170.51, 170.43, 70.62,
68.66, 68.18, 62.58, 62.32, 58.55, 44.33, 23.71, 21.22 (2C), 21.14 (2C)
ppm. MS (EI): m/z¼43(100%), 84(100%), 179(92%), 402(17%, Mþ1).
Anal. Calcd for C17H23NO10: C, 50.87; H, 5.78; N, 3.49; Found: C,
51.01; H, 5.49; N, 3.27.
obtained after recrystallization in EtOH.
25
Colorless needles, mp 198.0e199.6 ꢁC. [
a]
ꢀ33.7 (c 0.89,
D
CHCl3). FT-IR (neat) nmax¼3331, 2923, 1652, 1541, 1201, 803,
671 cmꢀ1 1H NMR (400 MHz, CDCl3):
.
d
¼7.10 (d, J¼7.3 Hz, 1H),
5.75e5.69 (m, 1H), 5.64e5.42 (m, 2H), 4.93 (s, 1H), 4.5 (br s, 1H),
4.40 (d, J¼11.9 Hz,1H, ABq), 4.24 (d, J¼11.9 Hz, 1H, ABq), 4.22 (s, 1H),
2.14 (s, 3H), 2.09 (s, 3H), 2.02 (s, 3H), 1.99 (s, 3H), 1.97 (s, 3H) ppm.
4.2.3. (1S,2R,3S,4S,5S,6R)-6-Acetamido-4-(acetoxymethyl)-5-chloro-
4-hydroxycyclohexane-1,2,3-triyl triacetate (14). To a solution of 12
(2.01 g, 5.0 mmol) inTHF (20 mL), glacial acetic acid (10 mL) followed
by aqueous KCl (3.73 g, 50.0 mmol) solution (20 mL) was added at
0e5 ꢁC. The mixture was stirred at rt for 48 h monitored by TLC
(developing solvent: DCM/EtOAc (1:1, v/v)) and solid NaHCO3 was
added carefully to neutralize the acid to pH¼7. The mixture was
extracted with dichloromethane (3ꢂ30 mL). The combined organic
phase was washed with brine (2ꢂ30 mL), dried over anhydrous
Na2SO4, filtered, concentrated under reduced pressure to afford
crude 15 as white crystalline solid. Colorless needle-shaped crystal
(1.76 g, 80%) was obtained recrystallization in EtOH.
13C NMR (101 MHz, CDCl3):
d
¼172.27, 170.78, 170.53, 170.20, 170.15,
78.06, 72.77, 70.43, 69.69, 69.50, 53.70, 24.12, 22.98, 21.48, 21.31,
21.26, 21.18 ppm. MS (EI): m/z¼43(100%), 162(73%), 384(69%),
530(23%, Mþ1). Anal. Calcd for C17H24INO10: C, 38.58; H, 4.57; N,
2.65; Found: C, 38.74; H, 4.73; N, 2.55.
4.2.6. (1S,2R,3S,4S,6S)-6-Acetamido-4-(acetoxymethyl)-4-hydroxycy
clohexane-1,2,3-triyl triacetate (penta-N,O-acetylvaliolamine) (13).
NaBH4 (760 mg, 20.0 mmol) was added to a solution of 15 (2.41 g,
5.0 mmol) in MeOH (25 mL) at rt with stirring. After stirring for 8 h
at the same temperature, the mixture was adjust to pH¼6e7 with
acetic acid and concentrated. The residual was dissolved in H2O
(25 mL) and extracted with dichloromethane (3ꢂ30 mL), washed
with brine (2ꢂ30 mL), dried over anhydrous Na2SO4, filtered,
concentrated under reduced pressure to afford crude 15. White
crystalline solid (1.82 g, 90%) was obtained after recrystallization in
MTBE/EtOH (1:1, v/v).
Colorless needles, mp 180.2e182.1 ꢁC. [
a
]
D
25 ꢀ18.4 (c 1.08, CHCl3).
FT-IR (neat) nmax¼3377, 1748, 1662, 1519, 1373, 1218, 1041, 931, 896,
832 cmꢀ1. 1H NMR (400 MHz, CDCl3):
d
¼6.97 (d, J¼9.7 Hz, 1H), 5.53
(dd, J¼17.2, 7.7 Hz, 1H), 5.48 (dd, J¼10.5, 4.4 Hz, 1H), 5.42 (d,
J¼9.2 Hz, 1H), 4.99 (dd, J¼6.3, 3.3 Hz, 1H), 4.48 (br s, 1H), 4.32 (d,
J¼12.3 Hz, 1H, ABq), 4.19 (d, J¼12.3 Hz, 1H, ABq), 4.14 (s, 1H), 2.14 (s,
3H), 2.09 (s, 3H), 2.02 (s, 3H), 2.00 (s, 3H), 1.97 (s, 3H) ppm. 13C NMR
(101 MHz, CDCl3):
d
¼172.49, 170.82, 170.57, 170.50, 170.21, 78.68,
White crystalline solid, mp 135.5e137.1 ꢁC (lit.12a 137e138 ꢁC);
20
71.85, 69.35, 68.98, 67.08, 56.83, 51.55, 24.09, 21.45, 21.29, 21.25,
21.14 ppm. MS (EI): m/z¼43(100%), 384(47%), 438(15%, Mþ1). Anal.
Calcd for C17H24ClNO10: C, 46.64; H, 5.53; N, 3.20. Found: C, 46.85;
H, 5.69; N, 3.06.
[
a
]
25 ꢀ14.4 (c 1.19, CHCl3) (lit.15
[
a
]
25 ꢀ19.6 (c 0.2, CHCl3), lit.12a
[a]
D
D
D
ꢀ17.8 (c 2.0, CHCl3)). FT-IR (neat) nmax¼2925, 1741, 1657, 1524, 1366,
1220, 1105, 1029, 933, 670 cmꢀ1. 1H NMR (400 MHz, CDCl3):
d
¼7.14
(d, J¼9.0 Hz, 1H), 5.51 (t, J¼10.3 Hz, 1H), 5.06 (d, J¼9.9 Hz, 1H), 4.91
(dd, J¼10.7, 4.4 Hz, 1H), 4.71 (dd, J¼4.5, 1.4 Hz, 1H), 3.98 (d,
J¼11.4 Hz, 1H, ABq), 3.85 (br s, 1H), 3.76 (d, J¼11.4 Hz, 1H, ABq), 2.06
(s, 3H), 2.03 (s, 3H), 1.98 (s, 3H), 1.97 (s, 3H), 1.96 (s, 3H) ppm. 13C
4.2.4. (1S,2R,3S,4S,5S,6R)-6-Acetamido-4-(acetoxymethyl)-5-bromo-
4-hydroxycyclohexane-1,2,3-triyl triacetate (15). To a solution of 12
(2.01 g, 5.0 mmol) in THF (20 mL), glacial acetic acid (10 mL) fol-
lowed by aqueous KBr (5.95 g, 50.0 mmol) solution (20 mL) was
added at 0e5 ꢁC. The mixture was stirred at rt for 18 h monitored by
TLC (developing solvent: DCM/EtOAc (1:1, v/v)) and solid NaHCO3
was added carefully to neutralize the acid to pH¼7. The mixture
was extracted with dichloromethane (3ꢂ30 mL). The combined
organic phase was washed with brine (2ꢂ30 mL), dried over an-
hydrous Na2SO4, filtered, concentrated under reduced pressure to
afford crude 15 as white crystalline solid. Colorless needle-shaped
NMR (101 MHz, CDCl3):
d
¼170.43, 170.32, 170.10, 170.06, 169.25,
74.56, 72.67, 71.85, 68.67, 65.95, 44.91, 32.62, 23.37, 20.61 (2C),
20.55, 20.34 ppm. MS(EI): m/z¼43(100%), 168(100%), 210(100%),
386(26%), 404(30%, Mþ1). Anal. Calcd for C17H25NO10: C, 50.62; H,
6.25; N, 3.47; Found: C, 50.23; H, 6.42; N, 3.38.
4.2.7. (1S,2S,3R,4S,5S)-5-Amino-1-(hydroxymethyl)cyclohexane-
1,2,3,4-tetraol ((þ)-valioamine) (6). Ba(OH)2 (8.6 g, 50.0 mmol) was
added to a suspension of 13 (2.02 g, 5.0 mmol) in water (50 mL). The
mixture was heated for 8 h at 80 ꢁC with stirring and cooled to room
temperature, and CO2 gas was bubbled through the mixture. The re-
sultant precipitate was filtered off and washed with water. The filtrate
and washing were combined then evaporated. The residual product
was dissolved with deionized water (250 mL) and Amberlite CG-50
(NHþ4 ) resin (100 mL) was added into the solution and stirred for
5 h. The resin obtained by filtration was washed with 1.0 M aqueous
ammonia (300 mL) and white solid was furnished with evaporating
filtrate under reduced pressure. The solid was redissolved with
deionized water (250 mL) and Dowex 1ꢂ2 (OHꢀ) (100 mL) was added
into the solution and stirred for 2 h to give free (þ)-valioamine (6)
(920 mg, 95%) with evaporating filtrate under reduced pressure.
Amorphouswhite solid, mp 176.5e180.3 ꢁC (lit.26 mp 178e180 ꢁC).
crystal (2.22 g, 92%) was obtained after recrystallization in EtOH.
25
Colorless needles, mp 192.5e193.8 ꢁC (ethanol). [
a]
ꢀ19.5 (c
D
0.99, CHCl3). FT-IR (neat) nmax¼2922, 2362, 1747, 1654, 1369, 1217,
1077, 1038, 891, 669 cmꢀ1 1H NMR (400 MHz, CDCl3):
.
d¼6.98 (d,
J¼9.7 Hz, 1H), 5.58 (dd, J¼7.5, 4.0 Hz, 1H), 5.55e5.47 (m, 2H), 4.99
(dd, J¼6.3, 3.3 Hz, 1H), 4.38 (br s, 1H), 4.33 (d, J¼12.3 Hz, 1H, ABq),
4.22 (d, J¼12.3 Hz, 1H, ABq), 4.13 (d, J¼1.4 Hz, 1H), 2.13 (s, 3H), 2.08
(s, 3H), 2.01 (s, 3H), 1.98 (s, 3H), 1.95 (s, 3H) ppm. 13C NMR
(101 MHz, CDCl3):
d
¼172.46, 170.77, 170.47, 170.43, 170.20, 78.40,
72.14, 69.47, 69.10, 68.34, 51.98, 46.88, 24.09, 21.45, 21.29, 21.24,
21.16 ppm. MS (EI): m/z¼43(100%), 384(63%), 482(15%, Mþ1 for for
79Br), 484(15%, Mþ1 for for 81Br). Anal. Calcd for C17H24BrNO10: C,
42.34; H, 5.02; N, 2.90; Found: C, 42.61; H, 4.89; N, 2.78.
[
a
]
25 þ17.8 (c 1.00, H2O) (lit.10
[
a
]
20 þ17.6 (c 0.52, H2O); lit.4 [
a
]
20 þ18.8
D
D
D
4.2.5. (1S,2R,3S,4S,5S,6R)-6-Acetamido-4-(acetoxymethyl)-4-hydroxy-
5-iodocyclohexane-1,2,3-triyl triacetate (16). To a solution of 12
(2.01 g, 5.0 mmol) in THF (20 mL), glacial acetic acid (10 mL) followed
by aqueous KI (8.30 g, 50.0 mmol) solution (30 mL) was added at
0e5 ꢁC. The mixture was stirred at room temperature for 18 h
monitored by TLC (developing solvent: DCM/EtOAc (1:1, v/v)) and
solid NaHCO3 was added carefully to neutralize the acid to pH¼7. The
mixture was extracted with dichloromethane (3ꢂ30 mL), washed
(c 1, H2O)). 1H NMR (400 MHz, D2O):
d
¼3.71 (t, J¼9.5 Hz,1H), 3.46 (d,
J¼6.4 Hz, 1H), 3.40 (d, J¼11.2 Hz, 1H), 3.35e3.27 (m, 2H), 3.22 (s, 1H),
1.77 (d, J¼15.1 Hz,1H),1.57 (d, J¼13.1 Hz,1H) ppm.13C NMR (101 MHz,
D2O):
d¼75.29, 72.55, 70.69, 69.78, 64.79, 51.04, 29.54 ppm.
4.2.8. (1S,2S,3R,4S,5S)-5-((1,3-Dihydroxypropan-2-yl)amino)-1-(hy-
droxymethyl)cyclohexane-1,2,3,4-tetraol (voglibose) (7). To a solution
of 6 (483 mg, 2.5 mmol) in DMF (30 mL), 1,3-dihydroxyacetone