7786 J . Org. Chem., Vol. 63, No. 22, 1998
Bernlind and Oscarson
3:2) to give 13 (174 mg, 107 µmol, 34%) and 126 mg (123 µmol,
39%) of the transacylated acceptor, (2,3,4,6-tetra-O-benzoyl-
â-D-glucopyranosyl)-(1f4)-7-O-acetyl-1,6-anhydro-2,3-di-O-
benzoyl-L-glycero-â-D-manno-heptopyranose.
gel chromatography (toluene/EtOAc 4:1) to yield 16 (68 mg,
36 µmol, 92%): 13C NMR δ 20.2, 21.1, 35.2, 61.2, 62.2, 63.4,
65.2, 67.2, 67.7, 68.3, 69.2, 69.6, 69.8, 70.3, 70.5, 70.6, 71.9,
72.4, 73.5, 74.5, 97.5, (J C,H ) 172 Hz), 99.1 (J C,H ) 173 Hz),
101.5 (J C,H ) 163 Hz), 121.8-137.0, 164.9-166.1, 169.7, 170.7.
2-(4-Tr iflu or oa cet a m id op h en yl)et h yl L-glycer o-r-D-
ma n n o-h eptopyr an osyl-(1f2)-[â-D-glu copyr an osyl-(1f4)]-
L-glycer o-r-D-m a n n o-h ep top yr a n ose (17). Compound 16
(64 mg, 34 µmol) was dissolved in MeOH (4 mL). The pH was
adjusted to 11 by addition of sodium methoxide (1 M in
MeOH), and the mixture was stirred for 5 h. Dowex H+ ion-
exchange resin was added to neutralize the solution. Filtration
and concentration gave crude 17, which was dissolved in H2O,
washed with Et2O, and purified by size-exclusion chromatog-
raphy on a Biogel P2 column (eluent H2O containing 1%
n-BuOH). Freeze-drying the product-containing fractions
yielded pure 17 (23 mg, 29 µmol, 88%): [R]D +32 (c 1.0, H2O);
13C NMR (D2O) δ 35.5, 61.5, 63.5, 63.6, 66.8, 68.9, 69.0, 69.6,
70.0, 70.3, 70.7, 70.9, 71.2, 72.4, 74.0, 76.3, 76.7, 77.0, 78.1,
98.6 (J C,H ) 172 Hz), 102.7 (J C,H ) 172 Hz), 103.3 (J C,H ) 161
Hz), 123.1, 130.7, 133.9, 138.9; 1H NMR (assorted peaks) δ
4.49 (J 1,2 ) 8 Hz), 4.90, 4.98. HRMS calcd for C30H43F3NO19
[M-H]- 778.2381, found 778.2438.
b. P r oced u r e B (SEt). Ethyl 2,3,4,6,7-penta-O-benzoyl-
1-thio-L-glycero-R-D-manno-heptopyranoside (180 mg, 232 µmol)
and 11 (157 mg, 171 µmol) were stirred under argon with
powdered molecular sieves (4A) in CH2Cl2/Et2O (1:2, 6 mL) at
room temperature for 45 min. DMTST (195 mg, 755 µmol)
was added, and the mixture was stirred overnight, when an
additional 90 mg (348 µmol) of DMTST was added. After the
mixture was further stirred overnight, more donor (170 mg,
219 µmol) and NIS (64 mg, 284 µmol) were added. The
mixture was left another night, whereafter it was diluted with
toluene and washed with Na2S2O3. Drying and filtration of
the organic phase followed by concentration gave a crude
product that was purified by silica gel chromatography (two
columns: toluene/EtOAc 4:1 and light petroleum (bp 40-65
°C)/EtOAc 3:2) to give 104 mg (63.8 µmol, 37%) of 13, 61 mg
(83.5 µmol) of hydrolyzed donor, 2,3,4,6,7-penta-O-benzoyl-1-
thio-L-glycero-R-D-manno-heptopyranose, and 73 mg (79.6
µmol, 47%) of unreacted 11. 13: [R]D -37 (c 1.0, CHCl3); 13C
NMR δ 20.7, 62.5, 63.0, 64.4, 65.6, 68.2, 68.7, 69.3, 69.6, 69.9,
70.1, 72.0, 72.8, 73.0, 73.4, 76.2, 78.5, 97.5, 101.0, 101.6, 128.1-
133.5, 164.7-166.0, 170.4.
(2,3,4,6,7-P en ta -O-ben zoyl-L-glycer o-r-D-m a n n o-h ep to-
p yr a n osyl)-(1f2)-[(2,3,4,6-tetr a -O-ben zoyl-â-D-glu cop yr a -
n osyl)-(1f4)]-1,6,7-tr i-O-a cetyl-3-O-ben zoyl-L-glycer o-r-
D-m a n n o-h ep top yr a n ose (14). To a solution of 13 (180 mg,
110 µmol) in acetic anhydride (10 mL) was added concentrated
sulfuric acid (50 µL) at room temperature. The mixture was
stirred for 20 min, at which time NaOAc (150 mg) was added.
The mixture was stirred for another 10 min, diluted with
toluene, and washed with NaHCO3 (10 mL, aq, sat.) and water.
The organic phase was dried (MgSO4) and concentrated. Silica
gel chromatography (toluene/EtOAc 4:1) of the residue afforded
14 (161 mg, 93 µmol, 85%): [R]D -27 (c 1.0, CHCl3); 13C NMR
δ 20.3, 20.9, 21.0, 61.2, 62.4, 63.7, 65.1, 67.1, 68.2, 69.3, 69.8,
Meth yl [2-(4-Tr iflu or oacetam idoph en yl)eth yl (2,3,4,6,7-
P en ta -O-ben zoyl-L-glycer o-r-D-m a n n o-h ep top yr a n osyl)-
(1f2)-[(2,3,4,6-tetr a-O-ben zoyl-â-D-glu copyr an osyl)-(1f4)]-
(6,7-d i -O -a c e t y l-3-O -b e n z o y l-L -g l yc er o-r-D -m a n n o-
h e p t op yr a n osyl)-(1f5)-4-O-b e n zyl-3-d e oxy-7,8-O-iso-
p r op ylid en e-r-D-m a n n o-oct-2-u lop yr a n osid ]on a te (18). A
mixture of 15 (79 mg, 45.6 µmol) and methyl [2-(4-trifluoro-
acetamidophenyl)ethyl 4-O-benzyl-3-deoxy-7,8-O-isopropylidene-
R-D-manno-oct-2-ulopyranosid]onate35 (19, 42 mg, 70.3 µmol)
in dry CH2Cl2 containing powdered molecular sieves (4 Å) was
stirred under argon at room temperature for 1 h. The solution
was cooled to -25 °C, NIS (16 mg, 71.1 µmol) and triflic acid
(1.5 µL, 17.0 µmol) were added, and the mixture was stirred
for 1 h, during which it was allowed to reach a temperature of
+5 °C. The reaction was quenched with the addition of
NaHCO3 (aq, sat., 1.5 mL) and Na2S2O3 (10% aq, 1.5 mL),
stirred for 10 min, and filtered through Celite. The organic
phase was separated and concentrated in vacuo. Coevapora-
tion of the residue from toluene followed by silica gel chroma-
tography (toluene/EtOAc 3:1) gave 18: (73 mg, 32.2 µmol,
71%). Further elution (toluene/EtOAc 1:1) rendered 12 mg of
unreacted 19. 18 [R]D -2.2 (c 1.0, CHCl3); 13C NMR δ 20.6,
21.4, 24.4, 26.3, 31.8, 35.4, 52.6 (OCH3), 62.5, 63.6, 63.8, 65.0,
65.2, 68.0, 68.4, 68.6, 69.5, 69.8, 70.3, 70.5, 70.9, 71.9, 72.0,
72.7, 73.3, 74.3, 74.4, 74.6, 98.4, 98.6 (J C,H ) 174 Hz), 99.2
(J C,H ) 171 Hz), 101.5 (J C,H ) 165 Hz), 109.3, 120.8-137.8,
70.1, 70.4, 71.0, 71.8, 71.9, 72.1, 73.3, 73.8, 75.5, 91.4 (J C,H
)
178 Hz), 99.0 (J C,H ) 172 Hz), 101.6 (J C,H ) 161 Hz), 127.9-
133.5, 164.9-166.0, 168.4, 169.8, 170.7. Anal. Calcd for
C
96H82O31: C, 66.6; H, 4.8. Found: C, 66.4; H, 4.7.
Eth yl (2,3,4,6,7-P en ta -O-ben zoyl-L-glycer o-r-D-m a n n o-
h ep top yr a n osyl)-(1f2)-[(2,3,4,6-tetr a -O-ben zoyl-â-D-glu -
cop yr a n osyl)-(1f4)]-6,7-d i-O-a cet yl-3-O-b en zoyl-1-t h io-
L-glycer o-r-D-m a n n o-h ep top yr a n ose (15). Ethanethiol (42
µL, 0.57 mmol) was added to a solution of 14 (139 mg, 80 µmol)
in CH2Cl2 (4 mL) containing powdered molecular sieves (4 Å),
and the mixture was stirred for 10 min at room temperature
under argon. Freshly distilled BF3 etherate (230 µL, 1.87
mmol) was added, and the mixture was stirred overnight.
NaHCO3 (aq, sat., 3 mL) was added, and the mixture stirred
for another 1 h, whereafter the organic phase was separated,
dried (MgSO4), and concentrated. Silica gel chromatography
(toluene/EtOAc 4:1) of the residue afforded unreacted 14 (18
mg, 13%) and 15 (115 mg, 66 µmol, 83%): [R]D -15 (c 1.0,
CHCl3); 13C NMR δ 14.9, 20.3, 21.1, 25.5, 60.7, 62.4, 63.7, 65.2,
67.5, 68.4, 69.4, 69.7, 69.9, 70.6, 70.7, 71.0, 71.8, 72.1, 73.4,
74.3, 79.0, 83.4, 99.0, 101.6, 127.9-133.5, 164.8-166.0, 169.8,
170.5. Anal. Calcd for C96H84O29S: C, 66.5; H, 4.9. Found:
C, 63.3; H, 4.7.
164.8-168.0, 170.1, 170.7. Anal. Calcd for C123H112F3NO38
C, 65.1; H, 5.0. Found: C, 65.0; H, 5.0.
:
Meth yl [2-(4-Tr iflu or oa ceta m id op h en yl)eth yl L-glyc-
er o-r-D-m a n n o-Hep top yr a n osyl-(1f2)-[â-D-glu cop yr a n o-
syl-(1f4)]-L-glycer o-r-D-m a n n o-h ep top yr a n osyl-(1f5)-3-
deoxy-r-D-ma n n o-oct-2-u lopyr an osid]on ate (20). Compound
18 (64 mg, 28 µmol) dissolved in aqueous acetic acid (80%, 3
mL) was heated at 70 °C for 3 h. The solution was concen-
trated, coevaporated from toluene (3 × 1.5 mL), and then
dissolved in MeOH (3 mL). The pH was adjusted to 12 by
treatment with a 1 M NaOMe solution in MeOH. The mixture
was stirred at room temperature for 3 h, neutralized with
Dowex 50 H+ ion-exchange resin, filtered, and concentrated.
The residue was dissolved in H2O, washed with diethyl ether,
and desalted on a Bio-Gel P2 column (eluted with distilled H2O
containing 1% of n-BuOH). The product-containing fractions
were freeze-dried, and the residue was dissolved in absolute
ethanol (3 mL). To the solution was added HOAc (200 µL, aq,
60% v/v) and palladium on activated carbon (10%, 13 mg). The
mixture was hydrogenolyzed at 9 atm for 16 h, filtered, and
concentrated in vacuo. The residue was once again purified
by size-exclusion chromatography as above to give 20 (25 mg,
24.3 mmol, 86%): [R]D +41 (c 1.0, H2O); 13C NMR (D2O) δ 35.0,
35.2, 54.1, 61.4, 63.5, 63.6, 63.8, 65.0, 65.8, 66.9, 69.0, 69.4,
69.5, 69.9, 70.3, 70.8, 71.1, 71.4, 72.3, 72.5, 74.0, 75.9, 76.2,
76.7, 77.3, 79.5, 99.3, 100.2 (J C,H ) 172 Hz), 102.8 (J C,H ) 169
2-(4-Tr iflu or oa ceta m id op h en yl)eth yl (2,3,4,6,7-P en ta -
O-ben zoyl-L-glycer o-r-D-m a n n o-h ep top yr a n osyl)-(1f2)-
[(2,3,4,6-tetr a -O-ben zoyl-â-D-glu cop yr a n osyl)-(1f4)]-6,7-
d i-O-a ce t yl-2-O-b e n zoyl-L -glycer o-r-D -m a n n o-h e p t o-
p yr a n osid e (16). 2-(4-Trifluoroacetamido)phenylethanol (20
mg, 92 µmol) was added to a solution of 15 (67 mg, 39 µmol)
in CH2Cl2/Et2O (1:1, 3 mL) containing powdered molecular
sieves (4 Å). After being stirred for 30 min, the mixture was
cooled (0 °C) and NIS (20 mg, 89 µmol) and triflic acid (1.4
µL, 16 µmol) were added. The ice bath was removed, and the
coupling was allowed to continue for 20 min, whereafter the
mixture was diluted (CH2Cl2) and filtered through Celite. The
filtrate was washed with Na2S2O3 (10% aq) and water, dried
(MgSO4), and concentrated. The residue was purified by silica