Simple syntheses of 4-O-glucosylated 1-deoxynojirimycins from maltose and cellobiose

Article abstract of DOI:10.1016/j.carres.2004.07.022

Glucosidase inhibitors α-d-glucopyranosyl-(1→4)-1- deoxynojirimycin and β-d-glucopyranosyl-(1→4)-1-deoxynojirimycin were prepared from maltose and cellobiose, respectively, via the corresponding 5,6-eno derivatives, their epoxidation and the subsequent double reductive amination of the resulting 5-uloses. In both cases, the reported route is the first chemical synthesis not based on enzymatic glucosyl transfer.

Full text of DOI:10.1016/j.carres.2004.07.022

Carbohydrate
RESEARCH
Carbohydrate Research 339 (2004) 2615–2619
Note
Simple syntheses of 4-O-glucosylated 1-deoxynojirimycins
from maltose and cellobiose
Andreas J. Steiner and Arnold E. Stutz*
¨
Glycogroup, Institut fu¨r Organische Chemie der Technischen Universita¨t Graz, Stremayrgasse 16, A-8010 Graz, Austria
Received 10 May 2004; accepted 22 July 2004
Available online 21 September 2004
Abstract—Glucosidase inhibitors a-D-glucopyranosyl-(1!4)-1-deoxynojirimycin and b-D-glucopyranosyl-(1!4)-1-deoxynojirimy-
cin were prepared from maltose and cellobiose, respectively, via the corresponding 5,6-eno derivatives, their epoxidation and the
subsequent double reductive amination of the resulting 5-uloses. In both cases, the reported route is the first chemical synthesis
not based on enzymatic glucosyl transfer.
Ó 2004 Elsevier Ltd. All rights reserved.
Keywords: Endoglucosidase inhibitor; a-D-Glucopyranosyl-(1!4)-1-deoxynojirimycin; b-D-Glucopyranosyl-(1!4)-1-deoxynojirimycin; 5-Ulose;
Intramolecular reductive amination
Iminosugars and related structures, including imino-
alditols, are powerful reversible inhibitors of glycosid-
ases. Inhibitors of endo-a-D-glucosidases have been
found useful for the treatment of diabetes type II symp-
toms,1 and the N-hydroxyethyl derivative of 1,5-
dideoxy-1,5-imino-D-glucitol (1-deoxynojirimycin) has
become a commercial product in this context.
OH
O
HO
HO
OH
OH
OH
H
N
H
N
O
HO
HO
HO
O
HO
O
HO
OH
OH
OH
1
2
For various purposes, O-glycosylated derivatives of
the inhibitors under consideration here are interesting
compounds. As such, these compounds could be useful
as more selective endoglucosidase inhibitors than the
parent compounds, could be useful for enzyme charac-
terisation, including active-site and sub-site mapping
and offer potential as prodrugs or slow-release agents
that have to be enzymatically ÔunwrappedÕ to liberate
the active monosaccharide inhibitor.
For the preparation of larger iminoalditol-containing
oligosaccharides, glycosylated inhibitors such as 1 and 2
may serve as substrates for enzymatic sugar chain
elongation.
knowledge, classical chemical O-glucosylations at O-4
of 1-deoxynojirimycin have not been conducted as yet.
Known chemical syntheses of related glycosylated
inhibitors in the D-galacto series4 require elaborate pro-
tecting group strategies and, consequently, are lengthy.
To avoid a chemical or enzymatic glycosylation step,
we have identified cellobiose and maltose as suitable
starting materials.
Cellobiose was conventionally converted into the cor-
responding methyl b-cellobioside by reaction of the per-
O-acetylated glycosyl bromide with methanol in the
presence of sodium methoxide.5 40,60-O-Protection was
achieved by formation of the known benzylidene acetal
36 (Scheme 1). Reaction of the latter with triphenylphos-
phine and iodine in the presence of imidazole following
GareggÕs procedure7 led smoothly to the corresponding
6-deoxy-6-iodo-D-cellobioside 4, which was subse-
quently per-O-acetylated to furnish 5. By treatment8
with silver fluoride in pyridine, the latter was efficiently
Both title compounds 1 and 2 have been found as nat-
ural products,2 and enzymatic syntheses exploiting gly-
cosidases have been reported.3 To the best of our
*
Corresponding author. Tel.: +43 0316 873 8247; fax: +43 0316 873
8740; e-mail: stuetz@orgc.tu-graz.ac.at
0008-6215/$ - see front matter Ó 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2004.07.022

2616
A. J. Steiner, A. E. Stu¨tz / Carbohydrate Research 339 (2004) 2615–2619
Ph
Ph
O
O
OH
I
O
O
a
b
O
O
O
O
O
O
HO
HO
OMe
OMe
HO
HO
OH
OH
OH
OH
3
4
Ph
Ph
O
O
I
O
O
c
e
d
O
O
O
O
O
O
AcO
AcO
AcO
OMe
OMe
AcO
OAc
OAc
OAc
OAc
5
6
Ph
Ph
O
O
AcO
O
O
O
HO
f
O
O
O
O
AcO
O
AcO
AcO
OMe
OAc
OAc
AcO
OAc
O
O
8
7
OH
OH
Ph
O
OH
O
H
N
O
O
g
O
HO
HO
O
O
O
HO
HO
HO
OH
OH
OH
OH
1
9
Scheme 1. Reagents and conditions: (a) Ph3P, I2, imidazole, toluene; (b) Ac2O, pyr.; (c) AgF, pyr.; (d) MCPBA, CH2Cl2; (e) silica gel; (f) NaOMe,
MeOH, then Amberlite IR 120 (H+), H2O; (g) H2, Pd(OH)2/C, NH4OH.
transformed into the 5,6-enosugar 6. Epoxidation of
enosugar 6 with 3-chloroperoxybenzoic acid based on
previous reports on the oxidation of 5,6-double bonds
in monosaccharides9 yielded the unstable 5,6-spiro-oxi-
rane 7, which was found to ring-open during column
chromatography on silica gel, and quantitatively convert
to the corresponding 1,6-anhydrosugar 8. Its structure
was assigned according to the large coupling constants
J2,3 and J3,4 (see Experimental) and by comparison with
values reported for monosaccharidic analogues.9 Subse-
thesised and converted into enosugar 13. Oxidation of
13 furnished spiro-oxirane 14 from which intermediate
ulose 15 was released by deprotection and subsequent
acidic hydrolysis.
1. Experimental
1.1. General methods
´
quent to deprotection of compound 8 under Zemplen
Melting points were recorded on a Tottoli apparatus
and are uncorrected. Optical rotations were measured
on a JASCO Digital Polarimeter or with a Perkin–Elmer
model 341 instrument with a path length of 10cm. NMR
spectra were recorded at 200 as well as 500MHz (1H),
and at 50 and 125MHz (13C). CDCl3 was employed as
solvent for protected compounds, and D2O as well as
MeOH-d4 for free sugars. Chemical shifts are listed in
d-units employing residual, not deuterated, solvent as
the internal standard. The signals of the protecting
groups were found in the expected regions and are not
listed explicitly. Structures of crucial intermediates were
unambiguously assigned by 1D TOCSY and HSQC
conditions, the ring nitrogen was introduced by stand-
ard double reductive amination with ammonia in water
under an atmosphere of hydrogen employing Pd(OH)2-
on-charcoal as the catalyst to furnish final product 1.
Likewise, employing the same sequence of steps
(Scheme 2), from the anomeric mixture of methyl malto-
sides that are available by conventional Fischer glycosyl-
ation of maltose, the corresponding a-D-glucopyranosyl
derivative 2 was prepared as follows: From acetal 10
(a,a-dimethoxytoluene, 4-toluenesulfonic acid, N,N-
dimethylformamide, following the standard procedure),
the corresponding deoxyiodo sugars 11 and 12 were syn-

A. J. Steiner, A. E. Stu¨tz / Carbohydrate Research 339 (2004) 2615–2619
2617
Ph
Ph
O
O
O
O
HO
O
O
HO
OH
I
HO
a
b
HO
O
O
O
O
HO
HO
OMe
OMe
OH
OH
10
11
Ph
Ph
O
O
O
O
O
O
I
c
e
d
AcO
AcO
AcO
O
AcO
O
O
O
AcO
AcO
OMe
OMe
AcO
AcO
13
12
OH
Ph
Ph
O
O
O
O
O
f
O
AcO
HO
O
O
AcO
HO
O
AcO
O
O
OMe
HO
OAc
OH
O
14
15
OH
O
HO
HO
OH
H
N
HO
O
HO
OH
2
Scheme 2. Reagents and conditions: (a) Ph3P, I2, imidazole, toluene; (b) Ac2O, pyr.; (c) AgF, pyr.; (d) MCPBA, CH2Cl2; (e) NaOMe, MeOH, then
Amberlite IR 120 (H+), H2O; (f) H2, Pd(OH)2/C, NH4OH.
experiments. TLC was performed on precoated alumin-
ium sheets (E. Merck 5554). Compounds were detected
by staining with concd H2SO4 containing 5% vanillin.
TLC detection of iminoalditols used a mixture of 10%
ammonium molybdate (w/v) in 10% aqueous sulfuric
acid containing 0.8% cerium sulfate (w/v).
For column chromatography Silica Gel 60 (E. Merck)
was used. The free inhibitors were chromatographed in
100:100:25:1 CHCl3–MeOH–H2O–concd aq ammonia.
reduced pressure, crude compound 4 was dissolved in
pyridine (45mL) and Ac2O (3.6mL, 38.1mmol), and a
catalytic amount of 4-dimethylaminopyridine was
added. MeOH (30mL) was added after 15h, and the sol-
vents were evaporated under reduced pressure. The
remaining material was partitioned between CH2Cl2
and 5% aq HCl. The organic layer was washed with
5% aq NaHCO3, dried (Na2SO4) and chromatographed
(7:2:1 cyclohexane–EtOAc–CH2Cl2) to give crystalline
20
compound 5 (2.18g, 93%): mp 264–265°C (dec); ½aꢀ
D
1
1.2. Methyl 2,20,3,30-tetra-O-acetyl-40,60-O-benzylidene-
6-deoxy-6-iodo-b-D-cellobioside (5)
ꢁ39.8 (c 1.7, CHCl3); H NMR (CDCl3): d 5.28 (dd,
1H, J3 ,4 9.8Hz, J2 ,3 9.3Hz, H-30), 5.19 (dd, 1H, J2,3
0
0
0
0
0
0
8.3Hz, J3,4 8.8Hz, H-3), 4.95 (dd, 1H, J1 ,2 7.8Hz, H-
To a mixture of 3 (Ref. 6) (1.44g, 3.24mmol) and toluene
(450mL), Ph3P (1.53g, 5.8mmol), imidazole (2.31g,
33.9mmol) and I2 (1.32g, 5.2mmol) were added, and
the mixture was vigorously stirred at 90°C for 3h until
solid deposited in the flask had become practically col-
ourless. Toluene was evaporated and the residue was
dissolved in 15:1 EtOAc–MeOH and passed over a
pad of silica gel to remove a large proportion of inor-
ganic material. After evaporation of the solvent under
20), 4.90 (dd, 1H, J1,2 7.8Hz, H-2), 4.72 (d, 1H, J1 ,2
0 0
7.8Hz, H-10), 4.45 (d, 1H, H-1), 4.37 (dd, 1H, J5 ,6 a
0
0
4.9Hz, J6 a,6 b 10.7Hz, H-60a) 3.73 (dd, J5 ,6 b 9.3Hz,
0
0
0
0
H-60b), 3.67 (dd, 1H, J4 ,5 9.3Hz, H-40), 3.66 (dd, 1H,
J4,5 8.8Hz, H-4), 3.60 (dd, 1H, J5,6 2.0Hz, J6a,6b
9.8Hz, H-6a), 3.52 (s, 3H, OMe), 3.50 (m, 1H, H-50),
3.32–3.24 (m, 2H, H-5, H-6b). 13C NMR: d 101.6,
101.2 (C-1, C-10), 80.7, 78.2, 73.8, 72.9, 72.85, 72.1,
71.9 (C-2, C-20, C-3, C-30, C-4, C-40, C-50), 68.7 (C-60),
0
0

2618
A. J. Steiner, A. E. Stu¨tz / Carbohydrate Research 339 (2004) 2615–2619
66.6 (C-50), 57.3 (OMe), 4.5 (C-6). Anal. Calcd for
C28H35IO14: C, 46.55; H, 4.88. Found: C, 46.51; H, 4.95.
Calcd for C27H32O15: C, 54.36; H, 5.41. Found: C,
54.29; H, 5.47.
1.3. Methyl 2,3-di-O-acetyl-4,6-O-benzylidene-b-D-glu-
copyranosyl-(1!4)-2,3-di-O-acetyl-b-D-xylo-hex-5-eno-
pyranoside (6)
1.5. b-D-Glucopyranosyl-(1!4)-1-deoxynojirimycin (1)
To a solution of anhydride 8 (680mg, 1.14mmol) in dry
MeOH, (50mL), NaOMe (1M in MeOH, 10 drops) was
added, and the mixture was kept for 24h at 0°C. Water
(40mL) was added, MeOH was largely removed under
reduced pressure, and the remaining aq solution was stir-
red with ion-exchange resin Amberlite IR 120 (H+) for
4h to release keto sugar 9. The resin was removed by fil-
tration, conc aq ammonia (20mL) and Pd(OH)2/C (20%,
200mg) were added to the solution, and the mixture was
stirred under an atmosphere of H2 at ambient pressure
for 72h. After removal of the catalyst by filtration and
evaporation of the solvent under reduced pressure, the
To a solution of 5 (1.90g, 2.63mmol) in pyridine
(60mL), AgF (2g, 16mmol) was added, and the mixture
was stirred at ambient temperature in the dark for 16h.
Et2O (300mL) was added, and the organic layer was
consecutively washed with satd aq Na2S2O3 and H2O.
The organic layer was dried (Na2SO4), the solvent was
evaporated under reduced pressure, and the remaining
residue was purified on silica gel (7:3 cyclohexane–
EtOAc) to give compound 6 (1.30g, 83%) as a colourless
20
D
1
syrup: ½aꢀ ꢁ94.8 (c 1.2, CH2Cl2); H NMR (CDCl3): d
5.30 (dd, 1H, J2 ,3 9.3Hz, J3 ,4 9.3Hz, H-30), 5.04 (dd,
remaining residue was chromatographed to give inhibi-
0
0
0
0
20
D
1H, J1 ,2 7.8Hz, H-20), 5.02 (dd, 1H, J2,3 4.9Hz, J3,4
7.3Hz, H-3), 4.94 (dd, 1H, J1,2 5.4Hz, H-2), 4.80 (br s,
1H, H-6a), 4.73 (d, H-10), 4.65 (d, 1H, H-1), 4.63 (br
tor 1 (90mg, 24%) as a slightly yellow glass: ½aꢀ +26.1
0
0
20
D
1
(c 0.3, H2O), lit.3a ½aꢀ +25.0 (c 0.42, H2O); H NMR
(D2O, HCl): d 4.42 (d, 1H, J1 ,2 8.3Hz, H-10), 3.82 (dd,
0
0
1H, J5 ,6 a 2.9Hz, J6 a,6 b 12.4Hz, H-60a), 3.81 (dd, 1H,
J5,6a 2.9Hz, J6a,6b 12.7Hz, H-6a), 3.65 (dd, 1H, J5,6b
0
0
s, 1H, H-6b), 4.40 (d, 1H, H-4), 4.37 (dd, 1H, J5 ,6 a
0
0
0
0
4.9Hz, J6 a,6 b 10.3Hz, H-60a), 3.77 (dd, 1H, J5 ,6 b
0
0
0
0
10.3Hz, H-60b), 3.71 (dd, 1H, J4 ,5 9.8Hz, H-40), 3.51
(s, 3H, OMe), 3.50 (m, 1H, H-50). 13C NMR: d 151.5
(C-5), 101.1 (C-1), 99.8 (C-10), 96.3 (C-6), 78.4 (C-40),
74.9 (C-4), 72.6, 72.4, 72.1, 72.0 (C-2, C-20, C-3, C-30),
68.7 (C-60), 66.6 (C-50), 56.9 (OMe). Anal. Calcd for
C28H34O14: C, 56.56; H, 5.76. Found: C, 56.61; H, 5.81.
6.0Hz, H-6b), 3.63 (dd, 1H, J5 ,6 b 5.8Hz, H-60b), 3.62
(dd, 1H, J1a,2 11.7Hz, J1b,2 4.8Hz, J2,3 9.3Hz, H-2),
3.49 (dd, 1H, J3,4 9.3Hz, J4,5 9.3Hz, H-4), 3.48 (dd,
0
0
0
0
1H, H-3), 3.40 (dd, 1H, J2 ,3 9.3Hz, J3 ,4 9.3Hz, H-30),
0
0
0
0
3.39 (ddd, 1H, J4 ,5 9.3Hz, H-50), 3.30 (dd, 1H, H-40),
3.26 (dd, 1H, H-20), 3.22 (dd, 1H, J1a,1b 12.2Hz, H-1a),
3.04 (ddd, 1H, H-5), 2.70 (dd, 1H, H-1b). 13C NMR: d
103.2 (C-10), 78.5 (C-2), 76.4 (C-4), 76.1 (C-3), 76.0 (C-
50), 75.9 (C-30), 73.7 (C-20), 70.1 (C-40), 61.1 (C-6), 59.8
(C-5), 58.8 (C-60), 47.1 (C-1).
0
0
1.4. 2,3-di-O-acetyl-4,6-O-benzylidene-b-D-glucopyrano-
syl-(1!4)-(5S)-2,3-di-O-acetyl-1,6-anhydro-5-C-hydroxy-
a-D-xylo-hexopyranose (8)
To a solution of 6 (1.02g, 1.71mmol) in CH2Cl2
(30mL), 3-chloroperoxybenzoic acid (55%, 610mg,
1.94mmol) and aq NaHCO3 (0.5M, 10mL) were added,
and the mixture was vigorously stirred at ambient tem-
perature for 90min. The organic layer was washed with
satd aq NaHCO3 and dried (Na2SO4). After evapora-
tion of the solvents under reduced pressure, the residue
was chromatographed. In contact with silica gel, unsta-
ble oxirane 7 was quantitatively converted into 1,6-
1.6. Methyl 2,20,3,30-tetra-O-acetyl-40,60-O-benzylidene-
6-deoxy-6-iodo-a,b-D-maltoside (12)
To a mixture of 10 (1.47g, 3.30mmol) and toluene
(450mL), Ph3P (1.53g, 5.8mmol), imidazole (2.31g,
33.9mmol) and I2 (1.32g, 5.2mmol) were added, and
the mixture was vigorously stirred at 90°C for 3h when
solid deposits in the flask had become practically colour-
less. Toluene was evaporated, the residue was dissolved
in 15:1 EtOAc–MeOH, and the solution was passed over
a pad of silica gel to remove a large proportion of inor-
ganic material. After evaporation of the solvent under
reduced pressure, crude deoxyiodo compound 11 was
dissolved in pyridine (45mL) and Ac2O (3.6mL,
38.1mmol) and a catalytic amount of 4-dimethylamino-
pyridine was added. MeOH (30mL) was added after
15h, and the solvents were evaporated under reduced
pressure. The remaining material was partitioned be-
tween CH2Cl2 and 5% aq HCl. The organic layer was
washed with 5% aq NaHCO3, dried (Na2SO4) and chro-
matographed (7:3 cyclohexane–EtOAc) to give an ano-
meric mixture of crystalline compounds 12 (2.21g,
anhydride 8 (910mg, 89%), which was isolated as a crys-
20
D
talline solid: mp 203–204°C (dec); ½aꢀ ꢁ17.8 (c 2.2,
1
CHCl3); H NMR (CDCl3): d 5.40 (d, 1H, J1,2 1.5Hz,
H-1), 5.32 (dd, 1H, J2 ,3 9.3Hz, J3 ,4 9.8Hz, H-30),
5.24 (dd, 1H, J2,3 8.3Hz, J3,4 9.3Hz, H-3), 4.96 (dd,
0
0
0
0
1H, J1 ,2 7.8Hz, H-20), 4.86 (d, 1H, H-10), 4.84 (dd,
0
0
0
0
0
0
1H, H-2), 4.30 (dd, 1H, J5 ,6a 4.9Hz, J6 a,6b 10.3Hz,
H-60a), 4.12 (d, 1H, H-4), 3.87 (d, 1H, J6a,6b 8.3Hz,
H-6a), 3.74 (dd, 1H, J5 ,6 b 9.8Hz, H-60b), 3.70 (dd,
0
0
1H, J4 ,5 9.4Hz, H-40), 3.54 (ddd, 1H, H-50), 3.38 (d,
0
0
13
1H, H-6b). C NMR: d 103.1 (C-5), 102.3 (C-10), 98.4
(C-1), 81.0, 78.4, 74.4, 72.5, 72.1, 71.7 (C-2, C-20, C-3,
C-30, C-4, C-40), 68.6, 68.0, 66.3 (C-50, C-6, C-60). Anal.

A. J. Steiner, A. E. Stu¨tz / Carbohydrate Research 339 (2004) 2615–2619
2619
92%). 13C NMR (CDCl3): d 100.8 (C-1/b), 97.0, 96.5,
96.4 (C-1/a, C-10/a, C-10/b), 79.1 (b), 79.0 (b), 76.4 (a),
76.1 (b), 75.5 (b), 72.6 (a), 72.5 (b), 72.0 (a), 71.6 (b),
70.8 (b), 70.7 (a), 69.2 (a), 69.1 (a), 68.7 (2 C), 67.2
(a), 64.3 (a), 64.25 (b), 57.2 (OMe/b), 55.9 (OMe/a),
8.2 (C-6/a), 6.6 (C-6/b). Anal. Calcd for C28H35IO14:
C, 46.55; H, 4.88. Found: C, 46.59; H, 4.93.
Water (40mL) was added, MeOH was largely evapo-
rated under reduced pressure, and the remaining aq
solution was stirred with ion-exchange resin [Amberlite
IR 120 (H+)] for 4h to release the 5-keto sugar 15.
The resin was removed by filtration, conc aq ammonia
(20mL) and Pd(OH)2/C (20%, 200mg) were added to
the solution, and the mixture was stirred under an
atmosphere of H2 at ambient pressure for 96h. After re-
moval of the catalyst by filtration and evaporation of
the solvent under reduced pressure, the remaining resi-
1.7. Methyl 2,3-di-O-acetyl-4,6-O-benzylidene-a-D-gluco-
pyranosyl-(1!4)-2,3-di-O-acetyl-a,b-D-xylo-hex-5-eno-
pyranoside (13) and methyl (5R,S)-2,3-di-O-acetyl-4,6-O-
benzylidene-a-D-glucopyranosyl-(1!4)-2,3-di-O-acetyl-5,6-
anhydro-5-hydroxy-a,b-D-xylo-hexopyranoside (14)
due was chromatographed to give inhibitor 2 (120mg,
20
D
30%) as a slightly yellow glass: ½aꢀ +104.2 (c 0.6,
20
H2O), lit.10 ½aꢀ +98 (c 0.1, H2O). 1H NMR (D2O,
D
HCl): d 5.25 (d, 1H, J1 ,2 3.9Hz, H-10), 3.77 (dd, 1H,
0
0
0 0
J5,6a 2.9Hz, J6a,6b 12.2Hz, H-6a), 3.74 (dd, 1H, J5 ,6 a
AgF (2.12g, 16.7mmol) was added to a solution of 12
(2.00g, 2.76mmol) in pyridine (60mL) and the mixture
was stirred at ambient temperature in the dark for
21h. Et2O (300mL) was added, and the organic layer
was consecutively washed with satd aq Na2S2O3 and
H2O. The organic layer was dried (Na2SO4), the solvent
was evaporated under reduced pressure and the remain-
ing residue was quickly purified on silica gel (7:3 cyclo-
hexane–EtOAc) to give an anomeric mixture of
compounds 13 (1.32g, 80%) as an unstable colourless
syrup that was immediately taken to the next step. 13C
NMR (CDCl3): d 152.0 (C-5/a), 151.1 (C-5/b), 96.6 (C-
6/a), 96.5 (C-6/b). Anal. Calcd for C28H34O14: C,
56.56; H, 5.76. Found: C, 56.53; H, 5.80.
2.4Hz, J6 a,6 b 11.7Hz, H-60a), 3.68 (dd, 1H, J5,6b
0
0
5.9Hz, H-6b), 3.64 (dd, 1H, J5 ,6 b 4.6Hz, H-60b), 3.63
0
0
(ddd, 1H, J4 ,5 10Hz, H-50), 3.59 (dd, 1H, J2 ,3 10Hz,
0
0
0
0
J3 ,4 10Hz, H-30), 3.58 (dd, J2,3 9.8Hz, J3,4 9.8Hz, H-
3), 3.56 (ddd, 1H, J1a,2 10.7Hz, J1b,2 4.9Hz, H-2), 3.50
0
0
0
0
(dd, J3,4 9.8Hz, J4,5 9.8Hz, H-4), 3.49 (dd, 1H, J1 ,2
0
3.9Hz, J2 ,3 9.8Hz, H-20), 3.30 (dd, 1H, H-40), 3.12
(dd, 1H, J1a,1b 12.7Hz, H-1a), 2.82 (ddd, 1H, H-5),
0
13
2.52 (dd, 1H, H-1b); C NMR: d 100.3 (C-10), 77.35
(C-4), 77.3 (C-3), 73.0 (C-30), 72.9 (C-20), 72.7 (C-50),
71.8 (C-2), 69.4 (C-40), 60.6 (C-6), 59.2 (C-60), 58.9 (C-
5), 46.7 (C-1).
To a solution of 13 (1.31g, 2.19mmol) in CH2Cl2
(30mL), 3-chloroperoxybenzoic acid (55%, 780mg,
2.49mmol) and aq NaHCO3 (0.5M, 10mL) were added,
and the mixture was vigorously stirred at ambient tem-
perature for 9h. The organic layer was washed with satd
aq NaHCO3 and dried (Na2SO4). After removal of the
solvents under reduced pressure, the residue was chroma-
tographed to give an anomeric mixture of diastereomeric
Acknowledgements
Financial support by the Austrian Fonds zur Fo¨rderung
der Wissenschaflichen Forschung (FWF), Vienna, Pro-
ject P 15726-N03 is appreciated.
References
oxiranes 14 (1.05g, 78%) as a colourless syrup. Main iso-
1
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5. Ho¨nig, H.; Weidmann, H. Synthesis 1975, 804.
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0
0
mer (of four): H NMR (CDCl3): d 5.39 (dd, 1H, J2 ,3
10.3Hz, J3 ,4 9.8Hz, H-30), 5.34 (dd, 1H, J2,3 7.8Hz,
0
0
J3,4 9.3Hz, H-3), 5.25 (d, 1H, J1 ,2 3.9Hz, H-10), 4.98
(dd, 1H, J1,2 5.9Hz, H-2), 4.79 (dd, 1H, H-20), 4.64 (d,
0
0
0
0
0
0
1H, H-1), 4.34 (dd, 1H, J5 6 a 4.6Hz, J6 a,6 b 9.8Hz, H-
60a), 4.28 (d, 1H, H-4), 3.96 (ddd, 1H, J5 ,6 b 10.3Hz,
H-50), 3.71 (dd, 1H, H-60b), 3.60 (dd, 1H, H-40), 3.47
(s, 3H, OMe), 3.16 (d, 1H, J6a,6b 4.9Hz, H-6a), 2.94 (d,
1H, H-6b). 13C NMR (main isomer): d 100.7 (C-1),
96.9 (C-10), 80.9 (C-5), 78.9 (C-40), 73.75 (C-3), 73.7 (C-
30), 73.0 (C-2), 71.6 (C-20), 70.9 (C-4), 68.9 (C-60), 63.0
(C-50), 57.0 (OMe), 49.2 (C-6). Anal. Calcd for
C28H34O15: C, 55.08; H, 5.61. Found: C, 55.14; H, 5.66.
0
0
8. Ferrier, R. J. J. Chem. Soc., Perkin Trans. 1 1979, 1455–
1458.
9. Enright, P. M.; Tosin, M.; Nieuwenhuyzen, M.; Cronin,
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3741.
1.8. a-D-Glucopyranosyl-(1!4)-1-deoxynojirimycin (2)
To a solution of spiro-oxirane 14 (750mg, 1.23mmol) in
dry MeOH (50mL), NaOMe (1M in MeOH, 10 drops)
was added, and the mixture was kept at 0°C for 24h.
10. Arai, M.; Sumida, M.; Fukuhara, K.; Kainosho, M.;
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