6464 J . Org. Chem., Vol. 63, No. 19, 1998
Auzanneau et al.
was allowed to reach +10 °C in 7 h under N2. Triethylamine
(50 µL, 0.36 mmol) was added, and the solids were filtered off
and washed with CH2Cl2 (70 mL). The combined filtrate and
washings were washed successively with H2O (100 mL), 1 M
HCl (100 mL), saturated aqueous NaHCO3 (100 mL), and
saturated aqueous NaCl (100 mL). The aqueous washings
were reextracted with CH2Cl2 (2 × 100 mL), and the combined
organic phases were dried and concentrated. Flash chroma-
tography (100:5, 1 L; 100:7, 0.5 L; 100:8, 0.5 L; toluene-EtOAc)
gave the disaccharide 10 (1.33 g, 76%). Impure fractions
containing mostly 10 were pooled, concentrated, and submitted
to chromatography to give more disaccharide 10 (164 mg, 9%).
Since the disaccharide thus obtained was contaminated with
trichloroacetamide, an analytical sample was purified by gel
permeation and crystallized on standing.
H-6′B), 3.97 (bs, 1 H, H-4B), 4.23 (bs, 1 H, H-3B), 4.27 (m, 2
H, H-5A, H-5A′), 4.36 (bd, 1 H, H-5B), 4.45 (m, 3 H, H-6A,
H-2A′, H-6A′), 4.60 (dd, 1 H, J 2,1 ) 8.5 Hz, J 2,3 ) 11 Hz, H-2A),
4.77 (dd, 1 H, J 6′,6 ) 12.5 Hz, J 6′,5 ) 3 Hz, H-6′A), 4.80 (dd, 1
H, J 6′,6 ) 12.5 Hz, J 6′,5 ) 2.5 Hz, H-6′A′), 5.03 (bs, 1 H, H-1B),
5.63 (m, 3 H, H-4A, H-1A′, H-4A′), 5.92 (d, 1 H, H-1A), 6.16
(dd, 1 H, J 3,4 ) 11 Hz, H-3A), 6.24 (dd, 1 H, J 3,2 ) 9.5 Hz, J 3,4
) 11 Hz, H-3A′), 7.22-8.15 (m, 38 H, aromatics). Anal. Calcd
for C76H59N5O22: C, 65.5; H, 4.3; N, 5.0. Found: C, 65.7; H,
4.4; N, 5.0.
1,6-An h y d r o -4-O -(3,4,6-t r i -O -b e n z o y l-2-d e o x y -2-
p h th a lim id o-â-D-glu cop yr a n osyl)-2-d eoxy-2-(((tr ich lor o-
eth oxy)ca r bon yl)a m in o)-â-D-glu cop yr a n ose (13). Palla-
dium-on-carbon catalyst (10%-on-C, 50% in H2O, 100 mg) was
added to a solution of the azide 10 (88 mg, 0.098 mmol) in
MeOH (10 mL), and the reaction mixture was stirred under
H2 at room temperature for 4 h. The catalyst was filtered off
and rinsed with MeOH (3 × 4 mL), and the combined filtrate
and washings were concentrated. Residual traces of water and
MeOH were coevaporated with anhydrous toluene (4 × 10 mL),
and the residual white solid was dissolved in anhydrous
CH2Cl2 (10 mL) and treated with NEt3 (150 µL, 1.08 mmol)
and trichloroethyl chloroformate (20 µL, 0.15 mmol). The
reaction mixture was stirred under N2 at room temperature
for 0.5 h, and more trichloroethyl chloroformate (14 µL, 0.1
mmol) was added. The reaction was left to proceed for 18 h
at room temperature and quenched by addition of MeOH (50
µL). The solution was diluted with CH2Cl2 (15 mL) and
washed successively with 1 M HCl (10 mL), saturated aqueous
NaHCO3 (15 mL), and brine (15 mL). The aqueous washings
were reextracted with CH2Cl2 (3 × 10 mL), and the combined
organic phases were dried and concentrated. Chromatography
of the residue (64:36 hexanes-EtOAc) gave the carbamate 13
Meth od B. Benzoyl chloride (83 µL, 0.71 mmol) was added
to a solution of the disaccharide 11 (100.3 mg, 0.127 mmol) in
anhydrous CH2Cl2 (9 mL) containing anhydrous pyridine (1
mL) and DMAP (10 mg). The reaction mixture was stirred at
room temperature for 3 days and worked up as described for
the preparation of 3 and 8 using method B. Chromatography
(9:1 and then 5:1 toluene-EtOAc) gave the disaccharide 10
(101.8 mg, 90%).
An a lytica l Da ta for 10. Mp: 116-118 °C. [R]20 ) +26
D
(c 1.0, CH2Cl2). 1H NMR: δ 3.19 (bs, 1 H, H-2B), 3.73 (dd, 1
H, J 6,6′ ) 7.5 Hz, J 6,5 ) 6 Hz, H-6B), 3.82 (bs, 1 H, H-4B), 4.01
(bd, 1 H, H-6′B), 4.48 (m, 2 H, H-5A and H-5B), 4.56 (dd, 1 H,
J 6,6′ ) 12.5 Hz, J 6,5 ) 6 Hz, H-6A), 4.71 (dd, 1 H, J 6′,5 ) 3 Hz,
H-6′A), 4.75 (dd, 1 H, J 2,1 ) 8.5 Hz, J 2,3 ) 10.5 Hz, H-2A), 5.40
(bs, 1 H, H-3B), 5.63 (bs, 1 H, H-1B), 5.74 (t, 1 H, J 4,3 + 4,5 ) 19
Hz, H-4A), 6.09 (d, 1 H, H-1A), 6.24 (dd, 1 H, J 3,4 ) 10 Hz,
H-3A), 7.20-8.05 (m, 24 H, aromatics). Anal. Calcd for
C
48H38N4O14: C, 64.4; H, 4.3; N, 6.3. Found: C, 64.3; H, 4.3;
N, 5.9.
1,6-An h yd r o-2-a zid o-4-O-(3,4,6-tr i-O-ben zoyl-2-d eoxy-
(62 mg, 60%) as a white powder. Mp: 125-127 °C. [R]20
)
D
-11 (c 1.05, CH2Cl2). 1H NMR: δ 3.70 (dd, 1 H, J 6,6′ ) 8 Hz,
2-p h th a lim id o-â-D-glu cop yr a n osyl)-2-d eoxy-â-D-glu cop y-
r a n ose (11) a n d 1,6-An h yd r o-2-a zid o-3,4-d i-O-(3,4,6-tr i-
O-ben zoyl-2-d eoxy-2-p h th a lim id o-â-D-glu cop yr a n osyl)-2-
d eoxy-â-D-glu cop yr a n ose (12). A suspension of the diol 4
(100 mg, 0.53 mmol) in anhydrous CH2Cl2 (30 mL) containing
4 Å activated molecular sieves (3 g) was stirred under N2 for
1 h at room temperature. A solution of TMSOTf in CH2Cl2
(0.16 M, 100 µL, 0.016 mmol) followed by a solution of the
trichloroacetimidate8 9 (41 mg, 0.054 mmol) in CH2Cl2 (100
µL) were added, and the reaction was monitored by TLC (3:1
toluene-EtOAc; Rf(11) 0.16, Rf(12) 0.37). More TMSOTf in
CH2Cl2 (0.16 M, 3 × 100 µL, 0.048 mmol) and more donor 9
(14 × 41 mg, 0.75 mmol) in CH2Cl2 (100 µL) were added
portionwise over 3 h, and the stirred reaction mixture was then
left for 18 h under N2 at room temperature. Triethylamine
(18 µL, 0.13 mmol) was added, and the molecular sieves were
decanted and washed with CH2Cl2 (10 mL). The combined
supernatant and washings were concentrated, and chroma-
tography (9:1 followed by 5:1 and 1:1 toluene-EtOAc) gave
the trisaccharide 12 contaminated with trichloroacetamide,
which was removed by gel permeation chromatography (55 mg,
7%), and the disaccharide 11 (200 mg, 47%). For analytical
purposes an aliquot of 11 was also submitted to gel permeation
while the remaining disaccharide was used directly in the
benzoylation step.
J 6,5 ) 6 Hz, H-6B), 3.75 (bs, 1 H, H-4B), 3.86 (bd, 1 H, J 2,NH
)
9.5 Hz, H-2B), 4.00 (bd, 1 H, H-6′B), 4.35 (bd, 1 H, H-5B), 4.47
(dd, 1 H, J 6,6′ ) 12 Hz, J 6,5 ) 7.5 Hz, H-6A), 4.54 (m, 1 H,
H-5A), 4.63 (d, 1 H, J ) 12 Hz, OCHHCCl3), 4.70 (dd, 1 H,
J 6′,5 ) 2 Hz, H-6′A), 4.75 (dd, 1 H, J 2,1 ) 8.5 Hz, J 2,3 ) 11 Hz,
H-2A), 4.85 (d, 1 H, OCHHCCl3), 5.38 (bs, 1 H, H-1B), 5.57
(bs, 1 H, H-3B), 5.66 (t, 1 H, J 4,3
) 19 Hz, H-4A), 5.69 (d,
+ 4,5
1 H, NHB), 6.04 (d, 1 H, H-1A), 6.29 (dd, 1 H, J 3,4 ) 9 Hz,
H-3A), 7.11-8.00 (m, 24 H, aromatics). Anal. Calcd for C51H41
-
Cl3N2O16: C, 58.7; H, 4.0; N, 2.7. Found: C, 58.8; H, 4.2; N,
2.7.
1,6-Di-O-a ce t yl-4-O-(3,4,6-t r i-O-b e n zoyl-2-d e oxy-2-
p h th a lim id o-â-D-glu cop yr a n osyl)-2-d eoxy-2-(((tr ich lor o-
eth oxy)ca r bon yl)a m in o)-r,â-D-glu cop yr a n ose (14). The
anhydro compound 13 (62 mg, 0.059 mmol) was dissolved in
9:1 Ac2O-CF3CO2H (20 mL), and the solution was stirred for
18 h at room temperature. Solvents were evaporated, and
residual traces of acid were coevaporated with toluene. Chro-
matography (6:4 hexanes-EtOAc) of the dry residue gave the
anomeric mixture of diacetate 14 (62 mg, 91%). 1H NMR in
CDCl3 showed an R:â ratio of 75:25. 1H NMR for the R-ano-
mer: δ 1.83, 2.18 (2 s, 2 × 3 H, CH3CO), 3.68 (dd, 1 H, J 6,6′
)
12 Hz, J 6,5 ) 3 Hz, H-6B), 3.76 (m, 1 H, H-5A), 3.87-4.07 (m,
2 H, H-6A and H-5B), 4.12-4.32 (m, 4 H, H-6′A, H-2B, H-4B
and H-6′B), 4.43 (d, 1 H, J ) 12 Hz, OCHHCCl3), 4.50 (dd, 1
H, J 2,1 ) 8.5 Hz, J 2,3 ) 11 Hz, H-2A), 4.64 (d, 1 H, OCHHCCl3),
5.24 (d, 1 H, J NH,2 ) 9.5 Hz, NHB), 5.54 (t, 1 H, J 4,3 + 4,5 ) 19.5
An a lytica l Da ta for 11. White powder. Mp: 103-105 °C.
[R]20 ) +17 (c 1.0, CH2Cl2). 1H NMR: δ 3.16 (bd, 1 H, J 2,3
)
D
5 Hz, H-2B), 3.36 (bd, 1 H, J OH,3 ) 4.5 Hz, OH-3B), 3.59 (dd,
1 H, J 6,6′ ) 7 Hz, J 6,5 ) 5.5 Hz, H-6B), 3.62 (bd, 1 H, J 4,3 ) 4.5
Hz, H-4B), 3.83 (d, 1 H, H-6′B), 3.87 (m, 1 H, H-3B), 4.30 (m,
1 H, H-5A), 4.32 (bd, 1 H, H-5B), 4.45 (dd, 1 H, J 6,6′ ) 12.5 Hz,
J 6,5 ) 6 Hz, H-6A), 4.66 (dd, 1 H, J 2,1 ) 8.5 Hz, J 2,3 ) 11 Hz,
H-2A), 4.82 (dd, 1 H, J 6′,5 ) 3 Hz, H-6′A), 5.25 (bs, 1 H, H-1B),
Hz, H-4A), 5.66 (dd, 1 H, J 3,2
) 9 Hz, J 3,2
) 11 Hz,
or 3,4
or 3,4
H-3B), 5.77 (d, 1 H, H-1A), 6.11 (dd, 1 H, H-3A), 6.15 (d, 1 H,
J 1,2 ) 3 Hz, H-1B), 7.20-8.20 (m, 24 H, aromatics).
1,6-Di-O-a ce t yl-4-O-(3,4,6-t r i-O-b e n zoyl-2-d e oxy-2-
p h th a lim id o-â-D-glu cop yr a n osyl)-2-d eoxy-2-(((tr ich lor o-
et h oxy)ca r b on yl)a m in o)-r-D-glu cop yr a n osyl Br om id e
(15). A solution of HBr in AcOH (33%, 800 µL) was added to
5.70 (t, 1 H, J 4,3
) 19.5 Hz, H-4A), 5.84 (d, 1 H, H-1A),
+
4,5
6.21 (dd, 1 H, J 3,4 ) 9.5 Hz, H-3A), 7.20-8.05 (m, 19 H,
aromatics). Anal. Calcd for C41H34N4O13: C, 62.3; H, 4.3; N,
7.1. Found: C, 62.3; H, 4.4; N, 6.9.
a solution of the diacetate 14 (49 mg, 0.043 mmol) in
anhydrous CH2Cl2 (2 mL). The reaction mixture was stirred
under N2 for 3 h at room temperature, and solvents were
evaporated. Residual acid was coevaporated with toluene (4
× 8 mL), and the residue was dissolved in CH2Cl2 (8 mL); this
solution was rapidly washed with aqueous saturated NaHCO3
An a lytica l Da ta for 12. White powder. Mp: 145-147 °C.
[R]20 ) +43 (c 1.0, CH2Cl2). 1H NMR: δ 2.72 (bs, 1 H, H-2B),
D
3.30 (dd, 1 H, J 6,6′ ) 7 Hz, J 6,5 ) 6 Hz, H-6B), 3.77 (bd, 1 H,