1004
M. Abert et al. / Carbohydrate Research 337 (2002) 997–1006
NMR, Tables 1 and 2. Anal. Calcd for C20H36N2O10:
C, 51.71; H, 7.81; N, 6.03. Found C, 51.65; H, 7.89; N,
6.07.
hydroxybenzotriazole (HOBT). The mixture was stirred
for 12 h at rt. After filtration of the formed dicyclo-
hexylurea (DCU), the solvent was removed under di-
minished pressure and the syrupy residue was purified
by column chromatography on silica gel with 19:1
EtOAc–MeOH as eluent. The product was crystallized
from EtOAc–hexane.
2,4;3,5-Di-O-methylene-6-O-nonylaminocarbonyl-N-
tris(hydroxymethyl)methyl- -gluconamide (4b). From 3b
D
(0.4 g) and TRIS; amorphous hygroscopic solid (0.44 g,
1
90%); [h]D +19.6° (c 1.0, CH2Cl2); H and 13C NMR,
Tables 1 and 2. Anal. Calcd for C22H40N2O10: C, 53.65;
H, 8.19; N, 5.69. Found C, 53.1; H, 8.14; N, 5.58.
2,4;3,5 - Di - O - methylene - N - tris(hydroxymethyl)me-
Methyl 6-deoxy-6-heptanecarboxamido-2,4;3,5-di-O-
methylene- -gluconate (6a). From 5 and octanoic acid
D
(0.69 g); white crystals (0.74 g, 52%); mp 120 °C; [h]D
1
thyl-6-O-undecylaminocarbonyl-
D
-gluconamide
(4c).
+16° (c 1.0, CH2Cl2); H and 13C NMR, Tables 1 and
From 3c (0.43 g) and TRIS; amorphous hygroscopic
2. Anal. Calcd for C17H29NO7: C, 56.81; H, 8.13; N,
3.90. Found C, 56.83; H, 8.07; N, 3.93.
Methyl 6-deoxy-2,4;3,5-di-O-methylene-6-nonanecar-
1
solid (0.35 g, 67%); [h]D +18.8° (c 1.0, CH2Cl2); H
and 13C NMR, Tables 1 and 2. Anal. Calcd for
C24H44N2O10: C, 55.37; H, 8.52; N, 5.38. Found C,
55.39; H, 8.56; N, 5.34.
boxamido- -gluconate (6b). From 5 and decanoic acid
D
(0.82 g); white crystals (0.82 g, 53%); mp 119.8 °C; [h]D
1
2,4;3,5-Di-O-methylene6-O-tridecylaminocarbonyl-N-
+18.5° (c 0.76, CH2Cl2); H and 13C NMR, Tables 1
tris(hydroxymethyl)methyl-
D
-gluconamide (4d). From 3d
and 2. Anal. Calcd for C19H33NO7: C, 58.90; H, 8.58;
N, 3.61. Found C, 58.93; H, 8.61; N, 3.57.
Methyl 6-deoxy-2,4;3,5-di-O-methylene-6-undecane-
(0.46 g) and TRIS; amorphous hygroscopic solid (0.33
g, 61%); [h]D +17.4° (c 1.0, CH2Cl2); 1H and 13C
NMR, Tables 1 and 2. Anal. Calcd for C26H48N2O10:
C, 56.92; H, 8.82; N, 5.11. Found C, 56.99; H, 8.87; N,
5.14.
carboxamido- -gluconate (6c). From 5 and dodecanoic
D
acid (0.96 g); white crystals (1.01 g, 61%); mp 124 °C;
1
[h]D +16° (c 0.65, CH2Cl2); H and 13C NMR, Tables
Methyl 6-amino-6-deoxy-2,4;3,5-di-O-methylene-
D
-
1 and 2. Anal. Calcd for C21H37NO7: C, 60.70; H, 8.98;
N, 3.37. Found C, 60.73; H, 9.01; N, 3.39.
gluconate (5).—Compound 2 (3 g, 12.8 mmol) was
dissolved in dry pyridine and tosyl chloride (3.65 g, 19.2
mmol) was added dropwise within 10 min. After stir-
ring for 24 h at rt, the solution was poured into cold
water and the aqueous layer was extracted twice with
EtOAc. The organic layer was washed with 1 N HCl,
satd NaHCO3, dried over sodium sulfate, and concen-
trated under diminished pressure. The resulting syrup
was purified by recrystallization in ether–hexane and
the ‘‘tosylated’’ compound was obtained as white crys-
tals (5.6 g, 93%). It (1.65 g, 3.5 mmol) was then
dissolved and sodium azide (0.7 g, 20.4 mmol) was
added in DMF (20 mL). The mixture was sonicated for
30 min at rt. The solvent was removed and the syrupy
residue was dissolved in EtOAc, concentrated to dry-
ness and purified by recrystallization in MeOH–ether.
The ‘‘azido’’ derivative was obtained as white crystals
(0.75 g, 83%). This latter compound (1.4 g, 5.4 mmol)
was dissolved in MeOH. After cooling the solution,
Pd–C (325 mg) was added. The mixture was hydro-
genated for 12 h. After filtration on Celite, the solvent
was removed under diminished pressure. Compound 5
was obtained as a clear oil (1.17 g, 93%); [h]D +10.5°
(c 1.0, MeOH); 1H and 13C NMR, Tables 1 and 2.
Anal. Calcd for C9H15NO6: C, 46.35; H, 6.48; N, 6.01.
Found C, 46.39; H, 6.55; N, 6.10.
General procedure for the synthesis of 6-alcanecarbox-
amido-6-deoxy-2,4;3,5-di-O-methylene-D-gluconic acid
(7a–c).—Compound 6a–c (1 mmol) was added to 3:2:1
MeOH–water–NaOH 1 N (50 mL) and stirred for 12 h
at rt. MeOH was removed under diminished pressure.
The pH was adjusted to 2–3 adding 1 N HCl. The
product was extracted twice by EtOAc. The solvent was
evaporated to dryness.
6-Deoxy-6-heptanecarboxamido-2,4;3,5-di-O-methyl-
ene- -gluconic acid (7a). From 6a (0.36 g); amorphous
D
hygroscopic solid (0.32 g, 95%); [h]D +17.2° (c 1.0,
MeOH); 1H and 13C NMR, Tables 1 and 2. Anal.
Calcd for C16H27NO7: C, 55.64; H, 7.88; N, 4.06.
Found C, 55.72; H, 7.93; N, 4.11.
6-Deoxy-2,4;3,5-di-O-methylene-6-nonanecarboxam-
ido- -gluconic acid (7b). From 6b (0.38 g); amorphous
D
hygroscopic solid (0.35 g, 94%); [h]D +20.2° (c 1.0,
MeOH); 1H and 13C NMR, Table 1 Table 2. Anal.
Calcd for C18H31NO7: C, 57.89; H, 8.37; N, 3.75.
Found C, 57.93; H, 8.41; N, 3.80.
6-Deoxy-2,4;3,5-di-O-methylene-6-undecanecarbox-
amido- -gluconic acid (7c). From 6c (0.41 g); amor-
D
phous hygroscopic solid (0.37 g, 94%); [h]D +31.4° (c
1
1.0, CH2Cl2); H and 13C NMR, Tables 1 and 2. Anal.
Calcd for C20H35NO7: C, 59.83; H, 8.79; N, 3.49.
Found C, 59.90; H, 8.77; N, 3.51.
General procedure for the synthesis of methyl 6-al-
canecarboxamido - 6 - deoxy - 2,4;3,5 - di - O-methylene-
D
-
General procedure for the synthesis of 6-alcanecarbox-
amido-6-deoxy-2,4;3,5-di-O-methylene-N-tris(hydroxy-
gluconate (6a–c).—To a solution of 5 (0.93 g, 4 mmol)
and the corresponding carboxylic acid (4.8 mmol) in
CH2Cl2 (50 mL) were added dicyclohexylcarbodiimide
(DCC) (0.99 g, 4.8 mmol) and a catalytic amount of
methyl)methyl-
D
-gluconamide
(8a–c).—Compound
7a–c (1.1 mmol) and tris(hydroxymethyl)methylamine
(0.2 g, 1.66 mmol) were dissolved in abs EtOH (50 mL).