J.-N. An et al. / Carbohydrate Research 341 (2006) 2200–2203
2201
detected by TLC in the reaction mixture. Due to the dif-
ficulty of purifying the product through chromatogra-
phy, the crude product was treated with CBzCl and
then subjected to flash chromatography. Along with
the expected final products 9, small amount of side
product 10 was obtained. The structure of 9 was fully as-
signed by NMR spectroscopy and mass spectrometry.
The structure of 10 was deduced based on NMR and
MS data, and the observed aromatization in the reduc-
tive amination in our early unpublished study. There-
fore, the undetermined side product of reductive
amination could be assumed to be 8 (Scheme 1).
3 or H-4), 7.35 (d, 4H, J 8.1 Hz, H–Ph), 7.78 (dd, 4H,
J 5.7, 8.1 Hz, H–Ph); 13C NMR (75 MHz, CDCl3): d
21.63 · 2 (CH3–Ph), 26.04 ((CH3)2C), 27.17 ((CH3)2C),
66.52, 67.92, 74.24, 84.99, 89.18, 111.44, 113.14
((CH3)2C quart, C-2 quart), 127.96 · 4, 129.96 · 4
(Ph), 132.30 · 2, 145.20 · 2 (Ph quart).
3.3. 6-Azido-6-deoxy-2,3-O-isopropylidene-1-O-
(p-toluenesulfonyl)-a-L-sorbofuranose (3)
To a solution of compound 2 (10.0 g, 18.9 mmol) in
anhyd DMF (40 mL) was added NaN3 (1.85 g,
28.4 mmol), and the suspension was heated at 75 ꢁC
for 30 h. The mixture was concentrated, and the result-
ing mixture was added to water (200 mL) and extracted
with EtOAc (800 mL). The organic layer was separated,
dried (MgSO4), and evaporated to give a crude yellow
product that was purified by flash chromatography. Elu-
tion with 14:1 petroleum–EtOAc afforded a white solid
Finally, the purified 1,6-dideoxynojirimycin hydro-
chloride was obtained after hydrogenation of 9, fol-
lowed by the addition of 0.1 N HCl and lyophilization
to give the product in 70% yield (based on 5).
CH3
CH3
N
Cbz
NH.HCl
H2, Pd(OH)2/C
0.1 N HCl
HO
HO
HO
HO
20
HO
9
HO
7.HCl
(6.72 g, 89%): mp 90–92 ꢁC; ½aꢀD +57.7 (c 1.04, CHCl3);
1H NMR (300 MHz, CDCl3): d 1.33 (s, 3H, (CH3)2C),
Reaction
1.49 (s, 3H, (CH3)2C), 2.46 (s, 3H, CH3–Ph), 3.44–3.56
0
(m, 2H, H-6), 4.15 (d, 2H, J1,1 10.5 Hz, H-1), 4.21 (br
s, 1H,), 4.26 (d, 2H, J1,1 10.5 Hz, H-10),4.31–4.37
0
3. Experimental
(ddd, 1H, H-5) 4.50 (s, 1H), 7.37 (d, 2H, J 8.4 Hz,
H–Ph), 7.80 (d, 2H, J 8.4 Hz, H–Ph); 13C NMR
(75 MHz, CDCl3): d 21.67 (CH3–Ph), 26.07 ((CH3)2C),
27.15 ((CH3)2C), 49.2 (C-6), 68.37 (C-1), 75.01, 80.07,
85.50, 111.29, 113.02 ((CH3)2C quart, C-2 quart),
128.00 · 2, 130.02 · 2(Ph), 132.29, 145.45 (Ph quart).
HRESIMS: Anal. Calcd for C16H21N3O7S: m/z
400.1184 [MH]+. Found: m/z 400.1186.
3.1. General
Melting points were measured on an X 4 melting point
apparatus. Optical rotations were measured at room
temperature (rt) using an AA-10 R automatic polari-
1
meter in a 0.1-dm cell. The H and 13C NMR spectra
were recorded on a Varian VXR 300 spectrometer.
The HRESIMS mass spectra were obtained using a
Bruker APE IV FTMS instrument. Reagents were either
dried by standard techniques or used as purchased.
3.4. 6-Azido-1,6-dideoxy-1-iodo-2,3-O-isopropylidene-
a-L-sorbofuranose (4)
To a solution of compound 3 (2.5 g, 6.27 mmol) in anhyd
DMF (20 mL) was added NaI (11.65 g, 62.7 mmol), and
the mixture was heated for 15 h at 110 ꢁC (bath temper-
ature). TLC with 2:1 petroleum–EtOAc then showed
that the reaction was almost complete. The mixture
was then cooled and the solvent was evaporated. The res-
idue was dissolved in water (50 mL), extracted with
CHCl3 (400 mL), and the CHCl3 layer was dried
(MgSO4), and evaporated to give a yellow syrup. The
crude product was purified by silica gel chromatography
using 15:1 petroleum–EtOAc to give a white solid
3.2. Preparation of 2,3-O-isopropylidene-1,6-bis-O-
(p-toluenesulfonyl)-a-L-sorbofuranose (2)
To a solution of 2,3-O-isopropylidene-a-L-sorbofura-
nose (10.0 g, 45.0 mmol) in anhyd pyridine (25 mL)
was added p-toluenesulfonyl chloride (21.67 g,
114.0 mmol) in batches, and the mixture stirred for 5 h
at rt. The mixture was concentrated, and the resulting
yellow syrup was dissolved with a large amount of
CHCl3 (600 mL). The organic layer was washed with
satd aq CuSO4 (75 mL) and water (35 mL), dried
(MgSO4), and evaporated to a yellow syrup. The crude
syrup was purified by flash chromatography using 10:1
petroleum–EtOAc to give compound 2 as a white solid
(23.52 g, 98.0%): mp 128–130 ꢁC, lit.10 131 ꢁC; 1H
NMR (300 MHz, CDCl3): d 1.30 (s, 3H, (CH3)2C),
1.43 (s, 3H, (CH3)2C), 2.45 (s, 6H, 2CH3–Ph), 4.04–
4.16 (m, 3H, 2H-6, H-1), 4.23–4.28 (m, 2H, H-1, H-3
or H-4), 4.38 (ddd, J 2.7 Hz, 1H, H-5), 4.44 (s, 1H, H-
20
(1.77 g, 79.7%): mp 53–55 ꢁC; ½aꢀD +40.6 (c 1.28,
1
CHCl3); H NMR (300 MHz, CDCl3): d 1.42 (s, 3H,
(CH3)2C), 1.51 (s, 3H, (CH3)2C), 3.51–3.67 (m, 4H,
2H-6, 2H-1), 4.28 (d, 1H, J 3 Hz,), 4.40 (ddd, 1H, H-
5), 4.50 (s, 1H); 13C NMR (75 MHz, CDCl3): d 7.37
(CH3-1), 26.43 (CH3)2C), 27.45 (CH3)2C), 49.22 (C-6),
75.58, 79.90, 86.51, 112.36 · 2 (CH3)2C quart, C-2
quart); HRESIMS: Anal. Calcd for C9H15IN: m/z
328.0051 [MHꢁN2]+. Found: m/z 328.0053.