D. Charon et al./Bioorg. Med. Chem. 6 (1998) 755±765
761
per million (ppm) relative to the signal of internal stan-
dards: Me4Si, d 0.0 (1H in CDCl3); d 77.0 (13C in
CDCl3); HDO, d 4.75 (1H in D2O); PPh3, d 0.0 (31P in
CDCl3). Assignments of signals was generally based on
2-D H-H and C-H COSY. Melting points (uncorrected)
were measured in capillaries with an Electrothermal
melting point apparatus. Infrared spectra were recorded
on a Perkin±Elmer 841 spectrophotometer in KBr
pellets. Column chromatography was performed on
Kieselgel 60 (Merck, 230±400 mesh). Thin-layer chroma-
tography (TLC) was performed on aluminum backed
precoated silica gel plates (Merck 60 F254), using detec-
tion with UV light and then charring with alcoholic
10% sulfuric acid. Reactions requiring anhydrous con-
ditions were conducted under a dry argon atmosphere.
Solvent removal was accomplished by a rotary eva-
porator operating at 45 ꢀC (bath) under reduced pres-
sure. Unless speci®ed, all commercially available
reagents were used without further puri®cation.
OMe), 3.45 (dd, J=4, 6.5 Hz, 1H, H2), 3.1 (dd, J=2.3,
6.5 Hz, 1H, H3).
Methyl 3-azido-2-benzamido-4,6-O-benzylidene-2,3-di-
deoxy-ꢀ-D-glucopyranoside (11) and methyl 2-azido-3-
benzamido-4,6-O-benzylidene-2,3-dideoxy-ꢀ-D-altropyr-
anoside (10). Sodium azide treatment of 28 g
(76.3 mmol) of the benzoylepiminoglycoside 9a accord-
ing to the original procedure of Guthrie22 aorded 7.8 g
(25%) of crystalline 3-azido-2-benzamido-glucoside (11)
melting at 220 ꢀC after crystallisation from isopropanol
and recrystallisation from EtOH (Lit.22 233±235 ꢀC
from isopropanol), and 21.8 g (70%) of the 2-azido
derivative (10) as a clear oil after ¯ash chromatography
eluting with EtOAc:cyclohexane, 6:4 (Rf 0.54, same sol-
vent). (11) 1H NMR (200 MHz, CDCl3) d 7.7±7.2 (m,
10H, Ar), 6.35 (d, J=9.4 Hz, 1H, NH), 5.6 (s, 1H,
PhCH), 4.76 (d, J=3.6 Hz, 1H, H1), 4.5 (dt, J=3.6,
10 Hz, 1H, H2), 4.33 (m , 1H, H6), 3.9 (t, J=10 Hz, 1H,
0
H3), 3.85 (m, 2H, H5, H6 ), 3.7 (t, J=10 Hz, 1H, H4),
Methyl 4,6-O-benzylidene-2,3-dideoxy-2,3-epimino-ꢀ-D-
allopyranoside (9). Tosyl chloride (31.5 g, 165 mmol)
was added to a stirred suspension of powdered potas-
sium hydroxide:potassium carbonate (1:2.5, 130 g) in
toluene:dimethylsulfoxide (1 L, 4:1) containing methyl
2-benzamido-4,6-O-benzylidene-2-deoxy-a-D-glucopyr-
anoside (8) (58 g, 150 mmol).29 After 30 min tetra-
butylammonium hydrogen sulfate (0.5 g) was added and
stirring was continued for 4 h. As TLC (EtOAc:cyclo-
hexane, 6:4) showed the absence of starting material the
mixture was diluted with toluene (1 L), the organic layer
was decanted from insoluble salts, washed with water,
dried (Na2SO4) and concentrated to a syrup crystallising
from chloroform (27 g, 70% in 2 crops), mp 145 ꢀC,
identical with the product obtained from a 3-O-mesyl
3.35 (s, 3H, OMe); Anal. calcd for C21H22N4O5: C, 61.5;
H, 5.4; N,13.65; found: C, 61.4; H, 5.2; N, 12.95. (10) 1H
NMR (200 MHz, CDCl3) d 7.8±7.2 (m, 10H, Ar), 7.15
(d, J=9 Hz, 1H, NH), 5.6 (s, 1H, PhCH), 4.94 (t d,
J=3, 8.7 Hz, 1H, H3), 4.75 (s, 1H, H1), 4.33 (dd, J=4.3,
9.9 Hz, 1H, H6), 4.14 (dd, J=4, 9.7 Hz, 1H, H4), 4.02 (
dt, J=4, 10 Hz, 1H, H5), 4.01 (bd, J=3 Hz, 1H, H2),
3.88 (t, J=9.9 Hz, 1H, H6), 3.35 (s, 3H, OMe). The oily
altroside (10) (1.5 g) was hydrogenated in methanolic
hydrogen chloride (50 mL, 0.0125%) at 1 atm and at
room temperature in the presence of 10% palladium on
charcoal (200 mg). Puri®cation by ¯ash chromatography
(CHCl3:MeOH, 9:1) gave 1 g of 2-amino-3-benzamido-
1
altroside as a yellow oil. H NMR (200 MHz, DMSO-
d6) d 7.8±7.2 (m, 10H, Ar), 5.65 (s, 1H, PhCH), 4.52 (s,
1H, H1), 4.5 (dt, 1H, H3), 4.35±4.05 (m, 3H, H4, H5,
derivative by Richardson30 (mp 141±145 ꢀC); H NMR
1
0
H6), 3.75 (t, J=10 Hz, 1H, H6 ), 3.35 (s, 3H, OMe), 3 (d,
(200 MHz, CDCl3) d 7.6±7.45 (m, 2H, Ar), 7.4±7.3 (m,
3H, Ar), 5.6 (s, 1H, PhCH), 4.9 (bs, 1H, H1), 4.2 (dd,
J=5, 10 Hz, 1H, H6), 4.1 (m, 1H, H5), 3.9 (bd,
0
J=10 Hz, 1H, H4), 3.65 ( t, J=10 Hz, 1H, H6 ), 3.45 (s,
3H, OMe), 2.7 ( bd, 2H, H2, H3).
J=2.5 Hz, 1H, H2). Acetylation of the above amino-
altropyranoside gave the 2-acetamido-3-benzamido
1
derivative as an oil. H NMR (200 MHz, CDCl3) d 7.8±
7.1 (m, 11H, Ar, NHCOPh), 6.4 (d, J=7.5 Hz, 1H,
NHAc), 5.45 (s, 1H, PhCH), 4.82 (t d, J=9, 2.5 Hz, 1H,
H3), 4.65 (s, 1H, H1), 4.3 (bd, J=7.5 Hz, 1H, H2), 4.2
(dd, J=10, 5 Hz, 1H, H6), 3.95 (m, 2H, H4, H5), 3.75 (t,
0
J=10 Hz, 1H, H6 ), 3.4 (s, 3H, OMe), 3.35 (s, 3H,
OMe), 1.95 (s, 3H, CH3CO ).
Methyl 4,6-O-benzylidene-2,3-benzoylepimino-2,3-dideoxy-
ꢀ-D-allopyranoside (9a). Benzoic anhydride (19 g,
84 mmol) was added to a solution of 9 (17.65 g,
67 mmol) in pyridine (230 mL). After 30 min as TLC
(EtOAc:cyclohexane) showed that benzoylation was
complete pyridine was distilled under vacuo, last traces
being removed by codistillation with toluene, and the
residue was crystallized from EtOH-CHCl3 aording
22.1 g (89.8%) of 9a as crystals melting at 190±191 ꢀC.
Lit.31,32,33 190±191 ꢀC, 194±195 ꢀC, 194±198 ꢀC. 1H
NMR (200 MHz, CDCl3) d 8.3 (d, J=7.5 Hz, 2H,
=CH-CO2-), 7.7±7.2 (m, 8H, Ar), 5.6 (s, 1H, PhCH), 5
(d, J=4 Hz, 1H, H1), 4.3 (m, 2H, H5, H6), 4 (dd, J=2.3,
2,3-Diamino-2,3-dideoxy-D-glucopyranose (12). The
azido-glucoside 11 (2.4 g) was hydrogenated in metha-
nolic hydrogen chloride (150 mL, 0.0125%) overnight
with Pd(OH)2 on carbon (20%, 500 mg) at room tem-
perature. The catalyst was removed by ®ltration, the
®ltrate was concentrated to dryness, and the residue
taken up in 5 N aqueous hydrogen chloride (100 mL).
After re¯uxing for 2.5 h as TLC (isopropanol: 20%
ammonia: H2O, 7:2:1) showed that hydrolysis was
0
8.4 Hz, 1H, H4), 3.8 (t, J=11.5 Hz, 1H, H6 ), 3.5 (s, 3H,