2844 J . Org. Chem., Vol. 62, No. 9, 1997
Pozsgay et al.
5-(Meth oxyca r bon yl)p en tyl 3,4,6-Tr i-O-a cetyl-r-D-glu -
cop yr a n osid e (45). A mixture of 44 (2.5 g, 4.77 mmol), 10%
Pd-C (200 mg), EtOH (50 mL), and AcOH (1 mL) was stirred
under hydrogen at 23 °C at 200 psi for 24 h. Removal of the
catalyst by filtration and the volatiles under vacuum followed
by column chromatographic purification (2:1 hexanes-EtOAc)
gave 45 (1.7 g, 83%) as a colorless syrup: [R]D +111° (c 1.3);
NMR (CDCl3) 1H, δ 5.22 (dd, 1 H, J ) 9.8, 9.6), 5.01 (dd, 1 H,
J ) 10.0), 4.91 (d, 1 H, J ) 3.9), 4.27 (dd, 1 H, J ) 4.6, 12.3),
4.07 (dd, 1 H, J ) 2.3), 3.95 (ddd, 1 H), 3.82-3.62 and 3.56-
3.46 (2 m, 3 H), 3.69 (s, 3 H), 2.35 (m, 2 H, J ) 7.3), 2.09, 2.08,
2.04 (3 s, 9 H), 1.76-1.62 (m, 4 H), 1.48-1.34 (m, 2 H); 13C, δ
173.9, 171.0, 170.6, 169.5, 98.2, 73.5, 70.8, 68.4, 68.0, 67.6, 62.0,
51.7, 33.8, 28.9, 25.6, 24.5, 20.9, 20.7, 20.6; CI-MS m/ z 452
[(M + NH4)+]. Anal. Calcd for C19H30O11: C, 52.53; H, 6.96.
Found: C, 52.36; H, 6.90.
5-(Meth oxyca r bon yl)p en tyl r-D-Glu cop yr a n osid e (46).
A solution of 45 (1.6 g, 3.7 mmol) in dry MeOH (10 mL) was
treated with NaOMe (cat.) at 23 °C for 12 h. The reaction
mixture was treated with Dowex (50 × 8-100, H+), filtered,
and then concentrated to give 46 (1.1 g, quantitative) as an
amorphous white solid: [R]D +101° (c 0.4, H2O); NMR (D2O)
1H, δ 4.89 (d, 1 H, J ) 3.9), 3.69 (s, 3 H), 2.41 (m, 2 H, J )
7.4), 1.72-1.58 (m, 4 H), 1.47-1.34 (m, 2 H); 13C, δ 178.4, 98.8,
73.9, 72.5, 72.1, 70.3, 68.7, 61.3, 52.9, 34.4, 29.0, 25.7, 24.8;
CI-MS m/ z 326 [(M + NH4)+]. Anal. Calcd for C13H24O8: C,
50.64; H, 7.85. Found: C, 50.66; H, 7.90.
5-(Hydr azin ocar bon yl)pen tyl r-D-Glu copyr an oside (47).
A solution of 46 (1.0 g, 3.1 mmol) in dry EtOH (5 mL) was
treated with hydrazine hydrate (2.5 mL) at 23 °C for 3 days.
The usual workup followed by column chromatographic puri-
fication of the residue (1:1 EtOAc-MeOH) gave 47 (800 mg,
80%) as an amorphous white solid: [R]D +99° (c 0.2, H2O);
NMR (D2O) 1H, δ 4.90 (d, 1 H, J ) 3.5), 2.23 (m, 2 H, J ) 7.4),
1.73-1.55 (m, 4 H), 1.45-1.28 (m, 2 H); 13C, δ 176.5, 98.8, 73.9,
72.5, 72.1, 70.3, 68.7, 61.3, 34.4, 29.0, 25.3 (2C); CI-MS m/ z
309 [(M + H)+], 326 [(M + NH4)+]. Anal. Calcd for C12H24
N2O7: N, 9.09. Found: N, 9.25.
69.0, 68.9, 68.6, 67.0, 62.1, 51.5, 33.9, 29.0, 25.6, 24.6, 21.0,
20.8, 20.7; CI-MS m/ z 924 [((M + NH4)+]. Anal. Calcd for
C49H62O15
: C, 66.05; H, 7.01. Found: C, 66.12; H, 7.05.
Further elution gave 50 (238 mg, 57%) as a colorless syrup:
1
[R]D +100° (c 1.1); NMR (CDCl3) H, δ 7.40-7.05 (m, 15 H),
5.89 (m, 1 H), 5.43 (dd, 1 H, J ) 9.5, 9.7), 5.27 and 5.18 (2 m,
2 H), 5.02 (d, 1 H, J ) 3.6), 4.99 (t, 1 H, J ) 9.7), 4.95 (d, 1 H,
J ) 3.3), 4.88, 4.81, 4.74, 4.58, 4.46, 4.45 (6 d, 12 H, J ) 10.9-
12.1), 4.27 (dd, 1 H, J ) 4.4, 12.2), 3.63 (s, 3 H), 3.45 (dd, 1 H,
J ) 9.5), 2.31 (m, 2 H, J ) 7.5), 2.09, 2.03, 1.96 (3 s, 9 H),
1.74-1.60 (m, 4 H), 1.50-1.34 (m, 2 H); 13C, δ 170.6, 170.0,
169.8, 138.7, 138.5, 137.8, 134.7, 128.3-127.4, 117.3, 97.0, 96.4,
81.4, 79.6, 77.2, 75.5, 75.4, 74.8, 73.5, 72.1, 71.6, 71.0, 68.8,
68.7, 68.1, 67.2, 62.1, 51.4, 33.9, 29.1, 25.7, 24.7, 20.9, 20.8,
20.7; CI-MS m/ z 924 [((M + NH4)+]. Anal. Calcd for
C49H62O15: C, 66.05; H, 7.01. Found: C, 66.16; H, 6.99.
5-(Meth oxyca r bon yl)p en tyl O-(3,4,6-Tr i-O-a cetyl-2-O-
ben zyl-r-D-glu cop yr a n osyl)-(1f2)-3,4,6-tr i-O-a cetyl-r-D-
glu cop yr a n osid e (52). Treatment of 45 (3.6 g, 8.2 mmol)
with the chloride 51 (6.0 g, 14.5 mmol) in the presence of Ag2-
CO3 (8.0 g, 29.0 mmol), 4 Å powdered molecular sieves (3 g),
and AgClO4 (600 mg, 2.9 mmol) in dry CH2Cl2 (60 mL) at 23
°C for 24 h under the conditions described for the preparation
of 49 gave, after column chromatography (2:1 hexanes-
EtOAc), 52 (5.2 g, 78%) as a colorless syrup: [R]D +119° (c
1
0.9); NMR (CDCl3) H, δ 7.40-7.25 (m, 5 H), 5.44 (2 t, 2 H),
4.98 (d, 1 H, J ) 3.7), 4.96 (2 t, 2 H), 4.88 (d, 1 H, J ) 3.3),
4.62 and 4.57 (2 d, 2 H, J ) 12.0), 4.31-4.00 (m, 6 H), 3.54
(dd, 1 H, J ) 9.4), 3.69-3.47 (m, 3 H), 3.66 (s, 3 H), 2.33 (m,
2 H), 2.09, 2.08, 2.04, 2.03, 2.01, and 1.98 (6 s, 18 H), 1.72-
1.59 (m, 4 H), 1.47-1.38 (m, 2 H); 13C, δ 174.0, 170.5-169.7,
137.4, 128.5-127.5, 98.1, 96.8, 77.6, 76.8, 73.1, 71.7 (2C), 68.9,
68.6, 68.4, 68.1, 67.2, 62.0, 61.4, 51.4, 33.8, 29.0, 25.6, 24.6,
20.8, 20.7, 20.6; CI-MS m/ z 830 [((M + NH4)+]. Anal. Calcd
for C38H52O19: C, 56.15; H, 6.45. Found: C, 56.01; H, 6.48.
5-(Meth oxyca r bon yl)p en tyl O-(3,4,6-Tr i-O-a cetyl-r-D-
glu cop yr a n osyl)-(1f2)-3,4,6-tr i-O-a cetyl-r-D-glu cop yr a -
n osid e (53). Treatment of 52 (5.2 g, 6.4 mmol) with 10%
Pd-C (300 mg) in EtOH (50 mL) and AcOH (1 mL) under H2
at 23 °C at 300 psi for 24 h under the conditions described for
the preparation of 45 gave 53 (4.0 g, 86%) as a white crystalline
material (iPr2O): mp 97-98 °C; [R]D +153° (c 1.3); NMR
5-[[(2-Am in oeth yl)am in o]car bon yl]pen tyl r-D-Glu copy-
r a n osid e (48). A solution of the ester 46 (250 mg, 0.8 mmol)
in ethylenediamine (2 mL) was stirred at 80 °C for 12 h. The
solution was concentrated under vacuum. Water was added
to and evaporated from the residue several times. Column
chromatographic purification of the residue (MeOH-EtOAc
1:1 then MeOH) afforded 48 (225 mg, 83%): [R]D +51° (c 0.4);
1
(CDCl3) H, δ 5.43 (dd, 1 H, J ) 9.9, 9.6), 5.12 (dd, 1 H, J )
9.6), 5.02 (dd, 1 H, J ) 9.8), 5.01 (d, 1 H, J ) 3.6), 4.99 (t, 1 H,
J ) 9.6), 4.96 (d, 1 H, J ) 3.7), 4.29 and 4.25 (2 dd, 2 H, J )
4.6, 12.2), 4.08 (2 dd, 2 H), 4.02-3.93 (m, 2 H), 3.89 (dd, 1 H,
J ) 9.9), 3.78-3.60 and 3.50-3.40 (2 m, 3 H), 3.68 (s, 3 H),
2.47 (d, 1 H, J ) 11.4), 2.34 (m, 2 H, J ∼ 7.5), 2.11, 2.09, 2.07,
2.06, 2.05, and 2.02 (6 s, 18 H), 1.72-1.61 (m, 4 H), 1.47-1.36
(m, 2 H); 13C, δ 170.7-169.5, 96.7, 95.4, 74.6, 73.1, 71.0, 70.5,
68.5, 68.4, 68.3, 67.6, 67.4, 61.9, 61.6, 51.5, 33.8, 29.0, 25.6,
24.5, 20.9, 20.71, 20.67, 20.6; CI-MS m/ z 740 [((M + NH4)+].
Anal. Calcd for C31H46O19: C, 51.52; H, 6.42. Found: C, 51.42;
H, 6.37.
1
NMR (D2O) H, δ 4.91 (d, 1 H, J ) 3.8), 3.26 (t, 2 H), 2.74 (t,
2 H), 2.29 (m, 2 H, J ) 7.4), 1.71-1.58 (m, 4 H), 1.47-1.32
(m, 2 H); 13C, δ 98.8, 73.9, 72.6, 72.1, 70.4, 68.7, 61.3, 42.4,
40.6, 36.4, 29.1, 25.9, 25.7; CI-MS m/ z 337 [(M + H)+] and
350 [(M + NH4)+]. Anal. Calcd for C14H28N2O7: N, 8.33.
Found: N, 8.24.
5-(Met h oxyca r b on yl)p en t yl O-(2-O-Allyl-3,4,6-t r i-O-
ben zyl-â-D-glu cop yr a n osyl)-(1f2)-3,4,6-tr i-O-a cetyl-r-D-
glu cop yr a n osid e (49) a n d 5-(Meth oxyca r bon yl)p en tyl
O-(2-O-Allyl-3,4,6-tr i-O-ben zyl-r-D-glu copyr an osyl)-(1f2)-
3,4,6-tr i-O-a cetyl-r-D-glu cop yr a n osid e (50). A mixture of
45 (200 mg, 4.6 mmol), 11 (330 mg, 6.5 mmol), Ag2CO3 (145
mg, 526 µmol), and 4 Å powdered molecular sieves (160 mg)
in dry CH2Cl2 (4 mL) was stirred at 23 °C for 1 h with exclusion
of light and then cooled to 0 °C. AgClO4 (50 mg, 241 µmol)
was added, and the mixture was stirred at 0 °C for 80 min
and then was filtered through celite. The insoluble material
was washed several times with CHCl3, and the combined
filtrate and washings were washed successively with saturated
aqueous NaHCO3 and H2O, dried (Na2SO4), and then concen-
trated. Column chromatography (2:1 hexanes-EtOAc) of the
residue gave 49 (73.2 g, 17.3%) as a colorless syrup: [R]D +51°
5-(Hyd r a zin oca r bon yl)p en tyl O-r-D-Glu cop yr a n osyl-
(1f2)-r-D-glu cop yr a n osid e (54). A solution of 53 (1.0 g, 1.4
mmol) in dry MeOH (20 mL) was treated with a catalytic
amount of NaOMe at 23 °C for 16 h. The mixture was
neutralized (Dowex 50 × 8-100, H+), filtered, and concen-
trated. A solution of the crude residue in EtOH (5 mL) was
treated with hydrazine hydrate (1.5 mL) at 23 °C for 12 h.
The usual workup followed by column chromatographic puri-
fication of the residue (MeOH) gave 54 (475 mg, 72%), which
was obtained as an amorphous white solid after freeze-
1
drying: [R]D + 131° (c 0.9, H2O); NMR (D2O) H, δ 5.15 and
5.08 (2 d, 2 H, J ) 3.7), 2.23 (m, 2 H, J ∼ 7.2), 1.74-1.58 (m,
4 H), 1.44-1.32 (m, 2 H); 13C, δ 176.6, 96.7, 95.9, 75.7, 73.5,
72.6, 72.4, 72.2, 72.1, 70.3, 70.2, 68.7, 61.3, 61.1, 34.4, 28.9,
25.67, 25.64; FAB-MS m/ z 471 [((M + 1)+], 493 [((M + Na)+].
Anal. Calcd for C18H34N2O12: N, 5.95. Found: N, 5.53.
5-(Meth oxyca r bon yl)p en tyl O-(4,6-Di-O-a cetyl-2-O-a l-
lyl-3-O-ben zyl-r-D-glu cop yr a n osyl)-(1f2)-O-(3,4,6-tr i-O-
a cet yl-r-D-glu cop yr a n osyl)-(1f2)-3,4,6-t r i-O-a cet yl-r-D-
glu cop yr a n osid e (55). A mixture of 53 (7.7 g, 10.7 mmol),
36 (10.6 g, 25.7 mmol), 2,6-di-tert-butyl-4-methylpyridine (6.0
g, 29.2 mmol), and 4 Å powdered molecular sieves (5 g) in dry
CH2Cl2 (110 mL) was stirred at 23 °C for 1 h and then was
1
(c 0.4); NMR (CDCl3); H, δ 7.40-7.10 (m, 15 H), 5.88 (m, 1
H), 5.47 (dd, 1 H, J ) 9.6), 5.25 and 5.12 (2m, 2 H), 5.07 (d, 1
H, J ) 3.6), 4.99 (dd, 1 H, J ) 9.9), 4.92, 4.81, 4.76, 4.56, 4.48,
4.47 (6 d, 12 H, J ) 10.7-12.1), 4.40 (d, 1 H, J ) 7.7), 4.29
(dd, 1 H, J ) 4.4, 12.3), 4.28-4.18 and 4.14-3.98 (2 m, 4 H),
3.76 (dd, 1 H, J ) 9.8), 3.73-3.36 (m, 7 H), 3.63 (s, 3 H), 3.28
(dd, 1 H, J ) 8.5), 2.30 (m, 2 H, J ∼ 7.5), 2.09, 2.02 (2 s, 9 H),
1.70-1.54 (m, 4 H), 1.44-1.32 (m, 2 H); 13C, δ 170.7, 170.3,
169.8, 138.5, 138.0, 137.9, 135.0, 128.4-127.6, 116.7, 104.6,
98.5, 84.6, 81.3, 77.4, 77.1, 75.7, 75.0, 74.6, 73.5, 73.4, 71.8,