1
886
J. Budka et al. / Tetrahedron 56 (2000) 1883–1887
repeated three times and the solid residue was then dried
under vacuum (1 Torr) at 80ЊC to give 0.46 g of dichloride 6
chloride 11 (97%). This compound was used for the next
reaction without further purification.
(97% yield).
Synthesis of derivative 12
The solution of the above prepared 6 in 20 ml of dry THF
was added dropwise to the mixture of 6-amino-6-deoxy-
The above prepared derivative 11 (0.62 g, 1.46 mmol) and
bis(2-amino-ethyloxy) derivative 10 (0.50 g, 0.68 mmol)
were dissolved in 20 ml of dry THF at room temperature
under N2 atmosphere. Then triethylamine (0.20 ml,
1.36 mmol) was injected via septum to this solution and
resulting mixture was stirred for 12 h at room temperature.
The reaction mixture was then poured into 40 ml of water
and extracted with chloroform (4×15 ml). The combined
1
,2;3,4-di-O-isopropylidene-a-d-galactopyranose 3 (0.34
g, 1.3 mmol) and triethylamine (0.18 ml) in 20 ml of dry
THF. The resulting mixture was stirred for 48 h at rt, then
poured into 40 ml of water and extracted with chloroform
(
4×15 ml). The combined organic layers were dried over
MgSO and then evaporated to dryness to yield 0.70 g of
4
crude product in the form of a brown oil. This oil was
purified by column chromatography on silica gel using
chloroform/ethyl acetate (5:1) mixture as an eluent to give
organic layers were dried over MgSO and evaporated to
4
dryness to yield 0.96 g of crude product as a purplish solid.
Pure product was obtained by the recrystallization from
dioxane/ethyl acetate (1:1) to give 0.50 g of 12 (49%,
0
.37 g of pure product 7 (52%, white solid), mp 168–171ЊC
2
0
(
7
ethanol). [a] Ϫ32 (c0.5, CHCl ); [Found: C, 66.96; H,
d
3
2
0
.83; N, 2.15. C H N O ·2H O requires C, 67.36; H,
white crystals), mp 167–169ЊC. [a] ϩ31 (c0.5,
7
2
98
2
16
2
d
1
8.02; N, 2.18%]; H NMR (CDCl ) d: 8.60 (d, 2H,
CHCl ); [Found: C, 62.02; H, 6.88; N, 1.81. C H N O
26
3
3
80 106
2
1
J3.8 Hz, –NH–), 7.21 (s, 2H, –OH), 7.03 (dd, 4H,
J2.2 Hz, J9.9 Hz, Ar–H), 6.83 (dd, 4H, J2.2 Hz,
J14.8 Hz, Ar–H), 5.32 (d, 2H, J5.0 Hz), 4.67 (d, 2H,
requires C, 62.07; H, 7.17; N, 1.81%]; H NMR (CDCl ) d:
3
8.56 (s, 2H, –OH), 8.22 (m, 2H, –NH–), 7.06 (d, 2H,
J2.2 Hz, Ar–H), 7.02 (d, 2H, J2.2 Hz, Ar–H), 6.99 (d,
2H, J2.2 Hz, Ar–H), 6.96 (d, 2H, J2.2 Hz, Ar–H), 5.67
(t, 2H, J4.9 Hz), 5.41 (m, 4H), 5.05 (m, 2H), 4.28 (dd, 4H,
J15.4 Hz, Ar–CH –Ar ax), 4.53 (dd, 2H, J2.2 Hz,
2
J7.7 Hz), 4.38 (d, 2H, J14.8 Hz, Ar–CH –Ar ax), 4.18
2
(
m, 8H), 3.37 (d, 2H, J13.9 Hz, Ar–CH –Ar eq), 3.28 (d,
t
J13.2 Hz, J28.0 Hz, Ar–CH –Ar ax), 4.26 (m, 4H,
2
2
2
H, J12.6 Hz, Ar–CH –Ar eq), 1.49 (s, 6H), 1.27 (s, 18H,
O–CH ), 4.16 (dd, 2H, J12.1 Hz, J3.9 Hz), 4.05 (m,
2
2
Bu ), 1.24 (s, 6H), 1.11 (s, 6H), 0.98 (s, 6H), 0.97 (s, 18H,
4H, N–CH ), 3.90 (dd, 2H, J12.1 Hz, J6.1 Hz), 3.38
2
t
Ϫ1
Bu ); IR (CHCl ) n
(cm ): 1669 (CvO), 3346, 3490
(dd, 4H, J20.3 Hz, J12.6 Hz, Ar–CH –Ar eq), 2.06 (s,
3
max
2
(
1
OH); MS FAB (C H N O ) calcd. 1246.7, found
247.2 (M ).
6H, CH CO), 2.05 (s, 6H, CH CO), 2.04 (s, 6H, CH CO),
7
2
98
2
16
3
3
3
ϩ
2.03 (s, 6H, CH CO), 1.90 (s, 6H, CH CO), 1.22 (s, 18H,
3 3
t t Ϫ1
Bu ), 1.12 (s, 18H, Bu ); IR (CHCl ) n
(cm ): 1681,
max
3
1
0
2
,3,4,5,6-Penta-O-acetyl-a-d-gluconic acid (11b). Freshly
1752 (CvO), 3310 (OH); MS FAB (C H N O ) calcd
80
106
2
26
ϩ
fused ZnCl (2.00 g, 14.7 mmol) was dissolved at room
1510.7, found 1511.5 (MH ).
2
temperature in 25 ml of acetic anhydride and the resulting
solution was cooled to Ϫ5ЊC. Sodium a-d-gluconate 11a
Synthesis of derivative 13
(6.4 g, 29 mmol) was then added and anhydrous hydrogen
chloride was bubbled through the stirred reaction mixture
while the temperature was maintained below 5ЊC. After
Sodium metal (1.00 g) was dissolved in 30 ml of absolute
methanol and to this solution was added derivative 12
30 min the stream of hydrogen chloride was stopped, the
(0.160 g, 0.106 mmol) in one portion. The course of the
cooling bath was removed and the milky coloured reaction
mixture was stirred at room temperature overnight. The
reaction mixture was cooled to 0ЊC, carefully quenched by
the addition of ice (30 g) and stirred for 1 h at room
temperature. The mixture was then diluted with 100 ml of
reaction was followed by TLC and after 10 min no starting
compound was detected. Then activated Dowex 50WX8
᭨
(
approx. 5 ml) was added and reaction mixture was stirred
overnight. The ion-exchange resin was removed by filtration
and the filtrate was evaporated to dryness to yield 115 mg of
product 13 (99%, white powder) with mp 176–180ЊC;
[Found: C, 63.51; H, 7.99; N, 2.35. C H N O ·2H O
water and extracted with CHCl (4×20 ml). The combined
3
organic extracts were dried over MgSO and evaporated to
4
60
86
2
16
2
1
dryness. The residue (yellowish oil) was evaporated three
times with 50 ml of toluene and dried in vacuum (1 Torr) at
requires C, 63.92; H, 8.05; N, 2.48%]; H NMR (CDCl )
3
d: 8.19 (brs, 2H), 7.64 (brs, 2H), 6.97 (s, 4H, Ar–H), 6.79 (s,
8
0ЊC overnight to yield 8.8 g of product 11b as a yellow oil.
4
H, Ar–H), 4.42, 4.27, 4.19, 3.98, 3.80, 3.70, 3.23, 2.00 (all
1
14
t
t
H NMR was in agreement with a published spectrum and
compound was used in the next reaction without further
identification.
signals very broad), 1.20 (s, 18H, Bu ), 0.96 (s, 18H, Bu );
13
C NMR (CDCl :CD OD, 4:1, v/v) d: 29.38, 30.66, 31.17,
3
3
3
7
1
1.30, 33.54, 33.78, 38.93, 63.15, 70.20, 71.24, 72.34,
3.72, 74.63, 124.95, 125.57, 127.78, 132.63, 142.52,
47.93, 148.60, 149.16, 175.21; MS (FAB) (C H N O )
15
2,3,4,5,6-Penta-O-acetyl-a-d-gluconyl chloride
(11).
60
86
2
16
ϩ
ϩ
Oxalyl chloride (3 ml, 34 mmol) was added dropwise to a
solution of the above-prepared compound 11b (0.61 g,
calcd 1090.60, found 1092.1 (MH ), 1114.1 (MϩNa ); IR
Ϫ1
(CHCl ) n
(cm ): 1653 (CvO), 3401(OH).
3
max
1.5 mmol) in 30 ml of carbon tetrachloride and the resulting
mixture was stirred at reflux for 3 h. The unreacted oxalyl
chloride and solvent was removed by distillation. The oily
Acknowledgements
residue was diluted with 5 ml of CCl and the solvent was
4
again distilled off to remove traces of (COCl) . This pro-
cedure was repeated three times and the oily residue was
then dried under vacuum (1 Torr) at 80ЊC to yield 0.62 g of
The authors thank Prof. Karel Kefurt (Department of
Chemistry of Natural Compounds, PICT) for helpful
discussion, Mrs Julie K ˇr elinov a´ (Institute of Organic
2