Notes
J . Org. Chem., Vol. 63, No. 14, 1998 4815
molecular sieves 4A (1.6 g) in anhydrous CH2Cl2 was stirred
under Ar for 1 h at room temperature and cooled to -20 °C.
BF3‚OEt2 (4.2 µL) was added to this cooled mixture, and the
resulting mixture was stirred for 1 h at -20 °C. The reaction
mixture was neutralized with Et3N and filtered through a Celite
pad, and the filtrate was concentrated. The residue was purified
by flash column chromatography (hexanes-EtOAc 2:1) to give
9 (93 mg, 22%) as a syrup: 1H NMR (CDCl3) δ 7.43-7.16 (15H,
m), 5.63 (1H, t, J ) 9.9 Hz), 5.27 (1H, dd, J ) 9.5, 10.8 Hz), 5.18
(1H, dd, J ) 2.9, 10.3 Hz), 5.06 (1H, d, J ) 2.8 Hz), 4.93 (1H, d,
J ) 11.5 Hz), 4.86 (1H, d, J ) 1.7 Hz), 4.81 (1H, d, J ) 12.1 Hz),
4.74-4.50 (4H, m), 4.16-4.00 (4H, m), 3.77-3.68 (4H, m), 3.43
(1H, ddd, J ) 3.3, 4.3, 10.9 Hz), 3.38 (3H, s), 2.02, 2.00, 1.99,
1.60 (3H×4, each s); 13C NMR (CDCl3) δ 170.4, 170.1, 169.6,
169.4, 138.5, 138.2, 138.1, 129.9, 128.7, 128.6, 128.4, 128.2, 127.8,
127.6, 127.5, 127.4, 127.3, 127.0, 126.9, 97.7, 81.0, 80.8, 76.6,
74.6, 74.5, 74.4, 73.4, 72.1, 71.7, 71.6, 70.8, 69.0, 61.0, 54.9, 39.0,
20.5, 20.2; HRFABMS calcd for C42H49O14S (M - H)+ 809.2843,
found 809.2840.
Meth yl 3-O-(2,3,4,6-Tetr a -O-a cetyl-5-th io-r-D-glu cop yr a -
n osyl)-2,4,6-tr i-O-a cetyl-r-D-m a n n op yr a n osid e (10). A sus-
pension of 9 (93 mg, 0.12 mmol) and 20% Pd(OH)2 on carbon
(Perlman’s catalyst; 60 mg) in MeOH was stirred under H2
atmosphere overnight at room temperature. The mixture was
filtered through a Celite pad, and the filtrate was concentrated.
The residue was hydrogenated under the same conditions three
more times until the TLC experiment (hexanes-EtOAc 1:4)
indicated that all the benzyl groups were removed. The residue
was acetylated with Ac2O and pyridine and purified by flash
column chromatography (hexanes-EtOAc 1:1) to give 10 (50 mg,
66%) as a syrup: 1H NMR (CDCl3) δ 5.38-5.22, (4H, m), 5.01-
4.97 (2H, m), 4.71 (1H, s), 4.39 (1H, dd, J ) 4.8, 12.1 Hz), 4.29
(1H, dd, J ) 3.6, 9.6 Hz), 4.22 (1H, dd, J ) 5.5, 12.2 Hz), 4.08
(1H, dd, J ) 2.7, 12.3 Hz), 4.06 (1H, dd, J ) 3.0, 12.1 Hz), 3.86
(1H, ddd, J ) 2.7, 5.4, 10.0 Hz), 3.63 (1H, ddd, J ) 3.2, 4.5, 10.4
Hz), 3.41 (3H, s), 2.24, 2.11, 2.07, 2.05, 2.04, 2.03, 1.98 (3H×7,
each s); 13C NMR (CDCl3) δ 170.6, 170.5, 169.7, 169.4, 98.7, 80.3,
74.8, 73.0, 71.7, 70.3, 69.9, 68.4, 62.5, 61.1, 55.2, 38.7, 20.8, 20.76,
20.72, 20.6, 20.5; HRFABMS calcd for C27H39O17S (M + H)+
667.1908, found 667.1905.
Meth yl 3-O-(5-Th io-r-D-glu cop yr a n osyl)-r-D-m a n n op y-
r a n osid e (4). A solution of 10 (50 mg, 75 µmol) in MeOH (1.4
mL) and 30% NaOMe in MeOH (24 µL) was allowed to stand
overnight at room temperature. The mixture was neutralized
with Dowex 50W-X8 [H+] resin, and the resin was filtered off.
The filtrate was concentrated, and the residue was purified on
a column of Sephadex G-25 with water. The fractions containing
4 were pooled and concentrated. The residue was lyophilized
from water to give 4 (28 mg, quantitative yield) as an amorphous
powder: 1H NMR (D2O) δ 5.16 (1H, d, J ) 2.7 Hz), 4.77 (1H,
brs), 4.19 (1H, dd, J ) 3.3, 9.5 Hz), 3.98-3.62 (9H, m), 3.44 (3H,
s), 3.18-3.11 (1H, m); 13C NMR (D2O) δ 101.6, 84.6, 78.4, 76.4,
74.7, 74.3, 73.6, 70.7, 67.4, 61.6, 60.8, 55.6, 44.1; HRFABMS
calcd for C13H25O10S (M + H)+ 373.1168, found 373.1169.
3-O-(2,3,4,6-Tetr a -O-a cetyl-5-th io-r/â-D-glu cop yr a n osyl)-
2,4-d i-O-b en zyl-N,6-O-ca r b on yl-1,5-d id eoxy-1,5-im in o-D-
m a n n itol (13). A suspension of 8 (354 mg, 0.695 mmol), 2,4-
di-O-benzyl-N,6-O-carbonyl-1,5-dideoxy-1,5-imino-D-mannitol (12)
(499 mg, 1.35 mmol), and activated molecular sieves 4A (2 g) in
anhydrous CH2Cl2 (7.9 mL) was stirred for 1 h at room
temperature and cooled to -78 °C. TMSOTf (20 µL) was added
dropwise to the cooled suspension, and the reaction mixture was
gradually warmed to 0 °C in a period of 2 h and stirred for an
additional 1 h at room temperature. Pyridine (2 mL) and Ac2O
(1.5 mL) were added to the mixture, and the resulting reaction
mixture was stirred overnight at room temperature. The
reaction mixture was diluted with CHCl3 and filtered through
a Celite pad. MeOH was added to the filtrate, and the resulting
solution was concentrated. The remaining solvent was coevapo-
rated with toluene several times. The residue was purified by
flash column chromatography (hexanes-EtOAc 1:1 f 1:2) to
give first the acetylated acceptor 3-O-acetyl-2,4-di-O-benzyl-N,6-
O-carbonyl-1,5-dideoxy-1,5-imino-D-mannitol (232 mg, 42%),
second the R-anomer of 13 (244 mg, 49%) as a white solid, and
finally the â-anomer of 13 (49 mg, 10%) as a syrup; 13R
(R-anomer): 1H NMR (CDCl3) δ 7.41-7.27 (10H, m), 5.62 (1H,
t, J ) 9.9 Hz), 5.27 (1H, dd, J ) 9.6, 10.8 Hz), 5.20 (1H, dd, J )
2.9, 10.4 Hz), 5.09 (1H, d, J ) 2.9 Hz), 4.99 (1H, d, J ) 12.1 Hz),
4.87 (1H, d, J ) 11.9 Hz), 4.62 (1H, d, J ) 12.1 Hz), 4.41 (1H, d,
J ) 11.9 Hz), 4.23 (1H, dd, J ) 2.5, 14.4 Hz), 4.21 (1H, t, J )
8.6 Hz), 4.11 (1H, dd, J ) 4.7, 12.4 Hz), 4.07 (1H, brs), 3.94 (1H,
t, J ) 9.3 Hz), 3.76 (1H, dd, J ) 3.7, 9.0 Hz), 3.73 (1H, dd, J )
2.8, 13.3 Hz), 3.69 (1H, dd, J ) 2.5, 9.7 Hz), 3.55 (1H, dt, J )
3.7, 8.5 Hz), 3.21 (1H, dt, J ) 3.8, 10.9 Hz), 2.88 (1H, d, J )
14.5 Hz), 2.05, 2.01, 1.99, 1.74 (3H×4, each s); 13C NMR (CDCl3)
δ 170.4, 169.9, 169.5, 169.3, 157.7, 137.9, 137.5, 128.7, 128.6,
128.1, 127.69, 127.67, 127.5, 83.9, 81.4, 76.4, 75.0, 74.5, 73.9,
71.9, 70.5, 70.4, 65.6, 60.8, 57.5, 40.9, 39.0, 20.8, 20.6, 20.5, 20.4;
HRFABMS calcd for C35H42NO13S (M + H)+ 716.2377, found
716.2374. 13â (â-anomer): 1H NMR (CDCl3) δ 7.44-7.28 (10H,
m), 5.45 (1H, t, J ) 9.1 Hz), 5.30 (1H, dd, J ) 9.6, 10.5 Hz), 5.08
(1H, t, J ) 9.4 Hz), 4.91 (1H, d, J ) 11.6 Hz), 4.79 (1H, d, J )
11.9 Hz), 4.57 (1H, d, J ) 8.8 Hz), 4.50 (1H, d, J ) 11.6 Hz),
4.45 (1H, d, J ) 11.9 Hz), 4.31-4.22 (3H, m), 4.09 (1H, dd, J )
3.5, 11.9 Hz), 3.90 (1H, brs), 3.87-3.82 (2H, m), 3.72 (1H, t, J )
9.1 Hz), 3.55-3.48 (1H, m), 2.97-2.91 (1H, m), 2.82 (1H, d, J )
14.6 Hz), 2.06, 2.04, 2.02, 1.91 (3H×4, each s); 13C NMR (CDCl3)
δ 170.4, 169.7, 169.3, 169.2, 157.7, 138.0, 136.9, 128.7, 128.6,
128.5, 128.44, 128.41, 128.3, 128.2, 128.1, 128.0, 127.7, 127.5,
80.7, 77.3, 75.2, 75.0, 74.4, 72.9, 71.8, 70.4, 69.4, 65.7, 61.5, 57.0,
41.0, 40.5, 20.6, 20.5; HRFABMS calcd for C35H42NO13S (M +
H)+ 716.2377, found 716.2380.
3-O-(2,3,4,6-Tet r a -O-a cet yl-5-t h io-r-D-glu cop yr a n osyl)-
N,6-O-ca r bon yl-1,5-d id eoxy-1,5-im in o-D-m a n n itol (14).
A
suspension of 13R (177 mg, 0.248 mmol) and 20% Pd(OH)2 on
carbon (160 mg) in MeOH (7 mL) was stirred under H2
atmosphere overnight at room temperature. The mixture was
filtered through a Celite pad, and the filtrate was concentrated.
The residue was purified by flash column chromatography
(CHCl3-MeOH 19:1) to give 14 (120 mg, 90%) as a syrup: 1H
NMR (CDCl3) δ 5.53 (1H, t, J ) 9.4 Hz), 5.31 (1H, dd, J ) 9.6,
10.8 Hz), 5.15-5.11 (2H, m), 4.45-4.35 (4H, m), 4.11 (1H, dd, J
) 3.4, 12.1 Hz), 4.07 (1H, dd, J ) 3.0, 11.0 Hz), 3.99 (1H, dd, J
) 2.3, 14.5 Hz), 3.72 (1H, dt, J ) 4.0, 10.8 Hz), 3.56 (1H, ddd, J
) 3.8, 7.8, 9.4 Hz), 3.47-3.43 (2H, m), 3.29 (1H, brs), 3.09 (1H,
dd, J ) 1.4, 14.5 Hz), 2.07, 2.06, 2.04, 2.02 (3H×4, each s); 13C
NMR (CDCl3) δ 170.8, 170.0, 169.9, 169.5, 158.4, 84.8, 81.0, 75.1,
72.1, 70.8, 68.3, 67.4, 65.6, 61.3, 58.0, 45.7, 39.1, 20.6, 20.5;
HRFABMS calcd for C21H30NO13S (M + H)+ 536.1438, found
536.1438.
3-O-(5-Th io-r-D-glu cop yr a n osyl)-1,5-d id eoxy-1,5-im in o-
D-m a n n itol (2). A solution of 14 (95.2 mg, 0.178 mmol) and
KOH (227 mg, 4.0 mmol) in 90% aqueous EtOH (4.6 mL) was
stirred for 4 h at 65 °C, and the mixture was cooled to 0 °C. The
cooled mixture was carefully neutralized to pH 7 with 1 M acetic
acid, and the resulting solution was concentrated. The residue
was chromatographed on silica gel (2-propanol-water-NH4OH
7:2:1) and subsequently with Sephadex G-25 (water) to 2 (44.7
mg, 63%) as an acetic acid salt after being lyophilized from water
for 4 days: 1H NMR (D2O) δ 5.18 (1H, d, J ) 2.8 Hz), 4.53 (1H,
brs), 4.11 (1H, t, J ) 10.0 Hz), 4.01 (1H, dd, J ) 3.1, 12.6 Hz),
3.95 (1H, dd, J ) 2.9, 9.8 Hz), 3.93-3.90 (3H, m), 3.85 (1H, dd,
J ) 3.0, 9.6 Hz), 3.77 (1H, dd, J ) 8.7, 9.6 Hz), 3.65 (1H, dd, J
) 8.7, 10.4 Hz), 3.42 (1H, dd, J ) 2.9, 13.6 Hz), 3.30 (1H, d, J )
13.6 Hz), 3.24-3.12 (2H, m), 1.93 (3H, s); 13C NMR (D2O) δ 84.5,
80.1, 76.3, 74.6, 74.3, 66.8, 66.5, 61.2, 60.9, 58.9, 48.3, 44.2;
HRFABMS calcd for C12H24NO8S (M - AcO)+ 342.1223, found
342.1222.
Meth yl 5-Th io-r-D-m a n n op yr a n osid e (16). A solution of
1,2,3,4,6-penta-O-acetyl-5-thio-R-D-mannopyranose 15 (3.03 g,
7.46 mmol) in methanolic HCl prepared from AcCl (6 mL) and
ice-cooled MeOH (60 mL) was stirred overnight at room tem-
perature in a tightly capped flask. The reaction mixture was
neutralized with saturated aqueous NaHCO3 and concentrated
to give a solid. The solid was suspended in hot EtOH (200 mL),
and the insoluble material was filtered off. The filtrate was
concentrated, and the residue was chromatographed on silica
gel (CHCl3-MeOH 9:1 f 4:1) to give 16 (1.4 g, 89%) as a syrup.
Spectral data of its tetraacetate were consistent with those
reported.24
Meth yl 2,4,6-Tr i-O-ben zoyl-5-th io-r-D-m a n n op yr a n osid e
(17). A suspension of 16 (1.4 g, 6.66 mmol) and Bu2SnO (2.0 g,
8.0 mmol) in MeOH (12 mL) was refluxed for 3 h, cooled, and
concentrated. A mixture of the residue, 4-methoxybenzyl chlo-