Transglucosidation of methyl and ethyl D-glucofuranosides by alcoholysis

Article abstract of DOI:10.1016/S0008-6215(01)00074-X

The acid catalyzed ethanolysis of methyl 5-O-methyl-α- and -β-D-glucofuranoside and the analogous methanolysis of ethyl 5-O-methyl-α- and -β-D-glucofuranoside have been investigated. For all four reactions, the primarily formed transglycosylation product was a single glycoside that had the opposite anomeric configuration to the starting material. This strongly indicates that a D-glucose methyl ethyl acetal is first formed and is then ring closed by a nucleophilic attack by HO-4, giving either the starting material or a transglycosylation product with the opposite anomeric configuration. Low percentages of the methyl ethyl acetals and of dimethyl acetals were also observed in the reaction product during the methanolysis reactions.

Full text of DOI:10.1016/S0008-6215(01)00074-X

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Carbohydrate Research 332 (2001) 33–39
Transglucosidation of methyl and ethyl
D-glucofuranosides by alcoholysis
Karl-Jonas Johansson,c Peter Konradsson,a,* Zygmunt Trumpakajb
aDepartment of Chemistry, Linko¨ping Uni6ersity, S-581 83 Linko¨ping, Sweden
bDepartment of Chemistry, Uni6ersity of Gdansk, PL-80-952 Gdansk, Poland
cArrhenius Laboratory, Department of Organic Chemistry, Stockholm Uni6ersity, S-106 91 Stockholm, Sweden
Received 29 September 2000; received in revised form 5 February 2001; accepted 1 March 2001
Abstract
The acid catalyzed ethanolysis of methyl 5-O-methyl-a- and -b-
of ethyl 5-O-methyl-a- and -b- -glucofuranoside have been investigated. For all four reactions, the primarily formed
transglycosylation product was a single glycoside that had the opposite anomeric configuration to the starting
material. This strongly indicates that a -glucose methyl ethyl acetal is first formed and is then ring closed by a
D-glucofuranoside and the analogous methanolysis
D
D
nucleophilic attack by HO-4, giving either the starting material or a transglycosylation product with the opposite
anomeric configuration. Low percentages of the methyl ethyl acetals and of dimethyl acetals were also observed in
the reaction product during the methanolysis reactions. © 2001 Elsevier Science Ltd. All rights reserved.
Keywords: Transglucosylation; Kinetics; Mechanistic studies
1. Introduction
et al.2 They showed that
acetal is formed during this reaction, and dis-
cussed its possible role as an intermediate in
the anomerization reaction.
D
-glucose dimethyl
From the observation that the dimethyl ac-
etals of
D
-glucose and
D
-galactose undergo
ring closure to furanosides concurrent with
their hydrolysis in aqueous acid, and that
these reactions were considerably faster than
In the present investigation, we have studied
the transglucosidation of methyl 5-O-methyl-
a- and -b- -glucofuranoside in ethanolic acid,
D
the hydrolysis of
D
-glyceraldehyde dimethyl
and of ethyl 5-O-methyl-a- and -b- -gluco-
D
acetal, Capon and Thacker1 draw the conclu-
sion that ring closure of the sugar acetals was
a concerted reaction, and that HO-4 provided
nucleophilic assistance. The corresponding
methanolyses of the sugar acetals were also
assumed to be concerted processes.
furanoside in methanolic acid.
2. Results and discussion
In order to avoid formation of pyranosides,
-glucofura-
A detailed kinetic study of the anomeriza-
the methyl and ethyl a- and -b-
D
tion of the methyl
D
-glucofuranosides in
nosides were methylated in the 5-position. The
starting material for all the glucofuranosides
acidic methanol was performed by Kaczmarek
was 5-O-methyl-a- -glucofuranosylurono-6,3-
D
lactone (1).3 On treatment with methanol or
* Corresponding author.
E-mail address: petko@ifm.liu.se (P. Konradsson).
ethanol and boron trifluoride etherate in
0008-6215/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0008-6215(01)00074-X

34
K.-J. Johansson et al. / Carbohydrate Research 332 (2001) 33–39
trimethyl or triethyl orthoformate, the methyl
-glucofura-
non-cyclic acetals with sufficient accuracy to
include them in the kinetic analysis.
(2) and ethyl (4) 5-O-methyl-a-
D
nosidurono-6,3-lactone, respectively, were ob-
tained. An analogous reaction, starting from
From these results, the ratio of the initially
formed glucosides could be determined, as
exemplified for the transglucosidation of ethyl
methyl-a-
has been reported.4 The corresponding methyl
(3) and ethyl (5) 5-O-methyl-b- -glucofura-
D
-glucofuranosylurono-6,3-lactone,
5-O-methyl-a-
In this scheme, a-Et stands for the ethyl 5-O-
-glucofuranoside (8), etc. the k1
D
-glucofuranoside (Scheme 1).
D
nosidurono-6,3-lactones were prepared by
methanolysis or ethanolysis of 1, respectively,
followed by chromatography on silica gel. Re-
duction of 2, 3, 4, and 5 with lithium alu-
minum hydride in THF yielded the desired
glucosides, namely, methyl (6) and ethyl (8)
methyl-a-
D
and (k2+k3) represent the rate constants for
the initial formation of b-Me and that of for
the equilibration of the initial formed product,
respectively.
The analytical solutions of the differential
equation system (gained form Scheme 1)
5-O-methyl-a- -glucofuranoside and methyl
D
(7) and ethyl (9) 5-O-methyl-b- -gluco-
D
df1/dt= −k1 f1
furanoside.
The methyl
D
-glucofuranosides were dis-
df2/dt=k1 f1−k2 f2+k3 f3
solved in 0.6 M ethanolic camphorsulfonic
acid (CSA), and the ethyl -glucofuranosides
df3/dt=k2 f2−k3 f3
(1)
(1a)
(1b)
(1c)
D
in 0.6 M methanolic camphorsulfonic acid.
The solutions were kept at 0 °C, samples were
withdrawn at intervals, neutralized with
Dowex 1X4-200 resin, concentrated, and
acetylated. The acetylated products were ana-
lyzed by GC and by GC–EIMS. In addition
has the following analytical solution
f1(t)=f1(0) exp(−k1t)
f2(t)=f1(0){A−B exp(−k1t)
−C exp[−(k2+k3)t]}
f3(t)=f1(0){1−A−(1−B) exp(−k1t)
+C exp[−(k2+k3)t]}
where
to the
D
-glucofuranosides, low percentages of
methyl ethyl (10) and dimethyl acetal (11)
were observed at the beginning and end, re-
spectively, of the methanolysis experiments,
and identified from their mass spectra. Typical
ions were those derived from C-1, namely m/e
89 and 75, respectively. The acetates of the
mixed acetals obtained on methanolysis of the
ethyl a- and b-glucofuranoside had different
retention times on GC, but had almost identi-
cal mass spectra. It was not, however, possible
to determine the relative proportions of the
k3
k2+k3
k3−k1
k2+k3−k1
A=
,
B=
,
C=A−B
At long time (t“ꢀ)
(1d)
(1e)
(1f)
f2eq/f3eq=k3/k2=A/(1−A)
At short time (kjtB1)
f2(t)=f1(0)[k1t−k1(k1+k2)t2/2+…]
f3(t)=f1(0)[k1k2t2/2−k1k2(k1+k2+k3)t3/6
+…]
(1g)
Eqs. (1f) and (1g) indicate that initially
formed product (b-Me) is proportional to t,
and initially formed product (a-Me) is propor-
tional to t2. All k1, k2 and k3 rate constants
can be estimated in similar way as in our
proceeding paper (Figs. 1–4).5
The results of the transglucosidation experi-
ments are summarized in Tables 1–4, and the
final results in Table 5.
Scheme 1. Transglucosidation of ethyl 5-O-methyl-a-D-gluco-
furanoside in methanolic CSA.

K.-J. Johansson et al. / Carbohydrate Research 332 (2001) 33–39
35
product was that with the inversed anomeric
configuration relative to the starting material.
This indicates that a methyl ethyl acetal with
inversed configuration at C-1 is the first
product formed. Ring closure, by attack of
HO-4, could proceed in two ways, either with
formation of the starting material or with
formation of the anomeric transglucosidation
product. The latter then reacts further to give
an anomeric mixture of glucosides. The reac-
tion sequence is exemplified in Scheme 2 for
the methanolysis of ethyl 5-O-methyl-a-
D
-glu-
cofuranoside (8).
Fig. 1. Transglucosidation of ethyl 5-O-methyl-a-D-glucofura-
noside in methanolic CSA. e6–e8 correspond to experimental
points and t6–t8 to theoretical curves.
In contradistinction, both anomers, with a
slight predominance of the product with in-
versed anomeric configuration, are initially
formed on the alcoholysis of the methyl and
ethyl 4-O-methyl-a- and b- -glucopyran-
D
osides,5 indicating that these reactions proceed
via a cyclic intermediate.
In conclusion, the results of the present
study are in full agreement with those of
Capon and Tucker1 and of Kaczmarek et al.2
On methanolyses of different methyl aldofuran-
osides under reducing conditions6 only non-
cyclic alditols were formed, also indicating a
non-cyclic intermediate. The results further
demonstrate that the transglucosidation in the
examples studied proceeds exclusively or al-
most exclusively via intermediate, non-cyclic
acetals.
Fig. 2. Transglucosidation of ethyl 5-O-methyl-b-D-glucofura-
noside in methanolic CSA. e6, e7, e9 correspond to experi-
mental points and t6, t7, t9 to theoretical curves.
In a related reaction, (1-O-methyl-
tol-1-yl)-N-p-nitroaniline was formed on
treatment of methyl a- -glucofuranoside with
D
-gluci-
D
Fig. 3. Transglucosidation of methyl 5-O-methyl-a-D-gluco-
furanoside in ethanolic CSA. e6, e8, e9 correspond to experi-
mental points and t6, t8, t9 to theoretical curves.
Fig. 4. Transglucosidation of methyl 5-O-methyl-b-D-gluco-
furanoside in ethanolic CSA. e7–e9 correspond to experimen-
tal points and t7–t9 to theoretical curves.
For all four transglucosidation reactions,
the only glucoside formed as a primary

36
K.-J. Johansson et al. / Carbohydrate Research 332 (2001) 33–39
Table 1
Methanolysis of ethyl 5-O-methyl-a-D-glucofuranoside in 0.6 M methanolic CSA at 0.090.1 °C
Time (s)
a-Et (mM)
Me Et acetal (mM)
b-Me (mM)
Di Me Acetal (mM)
a-Me (mM)
0
46
74
9.0
8.2
8.1
7.7
7.3
6.8
6.5
5.0
3.8
1.7
0.34
0.0
0.0
0.45
0.69
1.0
1.5
1.9
2.2
3.5
4.5
5.9
6.1
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.13
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.35
0.71
1.5
2.4
0.33
0.24
0.31
0.27
0.28
0.27
0.18
0.0
121
183
253
302
606
900
1816
3608
0.0
0.0
Table 2
Methanolysis of ethyl 5-O-methyl-b-D-glucofuranoside in 0.6 M methanolic CSA at 0.090.1 °C
Time (s)
b-Et (mM)
Et Me acetal (mM)
a-Me (mM)
Di Me acetal (mM)
b-Me (mM)
0
40
70
9.0
7.9
7.9
7.7
7.3
7.1
6.7
4.3
2.3
0.63
0.16
0.0
0.0
0.95
0.97
1.2
1.5
1.8
2.0
3.3
3.8
3.4
3.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.11
0.086
0.16
0.17
0.0
0.0
0.0
0.0
0.16
0.19
0.27
1.3
2.8
4.8
0.11
0.088
0.12
0.11
0.00
0.11
0.0
0.0
0.0
0.0
128
180
241
300
899
1804
3600
5403
5.7
the same sample refluxed for 7 days were
identical.
TLC was performed on 0.25 mm precoated
silica-gel plates (E. Merck, silica-gel 60 F254)
p-nitroaniline in methanolic hydrogen chlor-
ide under mild conditions.7 The absolute
configuration at C-1 was not determined but
is most probably (S), as in 9.
Table 3
Ethanolysis of methyl 5-O-methyl-a-
M ethanolic CSA at 0.090.1 °C
D-glucofuranoside in 0.6
3. Experimental
Time (s)
a-Me (mM)
b-Et (mM)
a-Et (mM)
General methods.—Methanol was distilled
over Mg/I2 and kept over 3 A molecular
,
0
120
180
238
294
9.6
9.1
8.9
8.7
8.6
7.7
6.7
4.7
3.4
2.3
1.3
0.65
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.26
0.72
1.2
1.5
2.1
2.4
0.52
0.69
0.87
0.98
1.9
2.6
4.2
5.1
5.7
sieves. Ethanol (99.5%) was dried over pow-
,
dered 3 A molecular sieves. CSA was recrys-
tallized from EtOAc and dried under reduced
pressure over P2O5. Titrations with 0.5 M
NaOH of freshly prepared 1 M CSA in
MeOH or EtOH and of the same solutions
that had been kept at 50 °C for 3 days
(MeOH) or for 5 days (EtOH) showed no
difference. 13C NMR spectra of 1 M CSA in
CD3OD, kept in a sealed NMR tube, and of
600
899
1799
2699
3608
5400
7214
6.3
6.6

K.-J. Johansson et al. / Carbohydrate Research 332 (2001) 33–39
37
Table 4
Merck silica-gel K 60 (0.040–0.063 mm) was
used.
Ethanolysis of methyl 5-O-methyl-b-
M ethanolic CSA at 0.090.1 °C
D-glucofuranoside in 0.6
NMR spectra was recorded on a Varian
Mercury 300 at 300 Hz instrument and chemi-
cal shifts were measured relative to acetone (l
31.0 ppm, CH3) or TMS as an internal stan-
dard. FAB-MS, in the positive mode, was
performed on a JEOL SX 102 instrument,
using a glycerol matrix. Optical rotations were
determined with on a Perkin–Elmer 241 po-
larimeter. GC was conducted on an HP 5890
instrument with a flame ionization detector
and hydrogen as carrier gas, using a HP-5
fused-silica capillary column. EI GC–MS was
conducted on an HP 5890-HP 5970 instru-
ment, using an HP-5MS fused-silica capillary
column and helium as carrier gas.
Time (s)
b-Me (mM)
a-Et (mM)
b-Et (mM)
0
599
900
1800
3601
9.6
9.3
9.1
8.3
7.0
6.0
5.1
2.7
2.0
1.5
1.1
0.75
0.55
0.0
0.35
0.52
0.89
1.3
1.5
1.7
2.2
2.4
2.5
2.5
2.4
2.5
0.0
0.0
0.0
0.43
1.3
2.0
2.8
4.7
5.2
5.6
6.0
6.4
6.6
5401
7199
14,398
17,999
21,599
25,200
28,800
32,836
Methyl 5-O-methyl h- -glucofuranosidu-
rono-6,3-lactone (2).—BF3 etherate (1.5 mL)
was added to MeOH (10 mL) and 0.2 mL
D
and detection by spraying the plates with 8%
aq H2SO4 solution, followed by heating at
250 °C. For column chromatography E.
Table 5
Mean rate constants (s−1) and (a/b) ratios for the initial transglucosidation reaction and for the equilibration of initially formed
product, on ethanolysis of methyl 5-O-methyl-a- and -b-
and -b- -glucofuranoside
D
-glucofuranoside and on methanolysis of ethyl methyl 5-O-methyl-a-
D
Starting material
104 k1 (s−1
)
104 k2 (s−1
)
104 k3 (s−1
)
k2/k3
R
Inversion a (%)
a-Me
b-Me
a-Et
3.990.02
0.8690.03
9.190.10
7.490.50
2.290.02
5.690.15
3.290.10
6.790.50
5.690.08
2.290.08
6.790.20
3.290.30
1/0.39
0.39
1/0.47
0.47
1.000
0.999
0.998
0.982
100
100
100
100
b-Et
a Inversion (%) of configuration during the initial reaction.
Scheme 2. Methanolysis of methyl 5-O-methyl-a-D-glucofuranoside in ethanolic CSA.

38
K.-J. Johansson et al. / Carbohydrate Research 332 (2001) 33–39
5.30 (1 H, d, H-1), 5.07 (1 H, dd, H-4), 4.95 (1
H, dd, H-3), 4.55 (1 H, d, H-5), 4.40 (1 H, dd,
H-2), 3.85 (2 H, m, CH2), 3.66 (2 H, m, CH2),
3.58 (3 H, s, CH3), 1.21 (3 H, t, CH3). [h]D+
147° (c 0.94, water). Mp 94–95°. Anal. Calcd
for C9H14O6: C, 49.54; H: 6.47. Found C,
49.62; H, 6.49.
of this solution was added to a solution of
5-O-methyl a-
-glucono-6,3-lactone3 (2.0 g,
D
10.5 mmol) in trimethyl orthoformiate (50
mL, dried over Drierite). The solution was
stirred for 1 h at rt and neutralized with Et3N.
After standard work up, 2 was isolated by
column chromatography (15:1, CHCl3–
MeOH). Crystallization from EtOAc gave 2 in
20% yield. [h]D+169° (c 0.98, water). Mp
113–114 °C. 13C NMR (D2O) l: 175.9 (C-6),
105.1 (C-1), 86.7 (C-3), 77.9 (C-5), 76.2 (C-2),
The synthesis also gave the b anomer as a
by-product in 5% yield
Ethyl 5-O-methyl i- -glucofuranosidurono-
D
6,3-lactone (5).—Dowex 50w-×8 (H+, 0.549
mg) was added to solution of 5-O-methyl
1
74.7 (C-4), 59.6 (CH3), 56.7 (CH3). H NMR
a-
-glucono-6,3-lactone3 (0.50 g, 2.6 mmol) in
D
(D2O) l: 5.18 (1 H, d, H-1), 5.06 (1 H, t, H-4),
4.95 (1 H, d, H-3), 4.55 (1 H, d, H-5), 4.42 (1
H, d, H-2), 3.59 (3 H, s, CH3), 3.47 (3 H, s,
CH3). Anal. Calcd for C8H12O6: C, 47.06; H:
5.92. Found C, 47.09; H, 5.90.
anhyd EtOH (10 mL and heated to 50 °C.
After 5 h the ion-exchange resin was filtered of
and the solution concentrated under reduced
pressure. The resulting syrup was purified by
column chromatography (9:1, CHCl3–
MeOH), and gave 5 in 71% yield. [h]D −21°
(c 1.1, CHCl3). 13C NMR (D2O) l: 176.2
(C-6), 108.6 (C-1), 84.6 (C-3), 77.9 (C-5), 76.8
(C-2), 76.6 (C-4), 64.7 (CH2), 59.4 (CH3), 14.4
Methyl
5-O-methyl
i- -glucofuranosi-
D
durono-6,3-lactone (3).—Dowex 50w-×8
(H+, 0.510 g) was added to a solution of
5-O-methyl a-
-glucono-6,3-lactone3 (0.514 g,
D
2.7 mmol) in MeOH (10 mL) and kept at
50 °C. After 5 h the resin was filtered off and
the solution was concentrated to dryness.
Column chromatography (39:1, CHCl3–
MeOH) of the syrup, followed by crystalliza-
tion from EtOAc–hexane gave 3 in 47% yield.
[h]D −14° (c 0.86, water). Mp 100 °C. 13C
NMR (D2O) l: 176.0 (C-6), 110.0 (C-1), 84.6
(C-3), 77.9 (C-5), 76.9 (C-2), 76.8 (C-4), 59.5
1
(CH3). H NMR (D2O) l: 5.21 (1 H, t, H-4),
5.16 (1 H, s, H-1), 5.05 (1 H, d, J3,4 4.4 Hz,
H-3), 4.45 (1 H, d, H-5), 4.34 (1 H, s, H-2),
3.76 (1 H, m, CH2), 3.59 (3 H, s, CH3), 3.47 (1
H, m, CH2), 1.07 (3 H, t, CH3). Anal. Calcd
for C9H14O6: C, 49.54; H: 6.47. Found C,
49.38; H, 6.40.
Methyl
5-O-methyl-h- -glucofuranoside
D
(6).—A solution of 2 (128 mg, 630 mmol) and
lithium aluminum hydride (62 mg, 1.6 mmol)
in freshly distilled THF (10 mL) was refluxed
for 1 h. A second portion of lithium alu-
minum hydride (31 mg, 820 mmol), was added
after the solution had reached rt. After 1 h the
reaction was quenched with an excess of
Na2SO4·10 H2O and filtered through Celite.8
The filtrate was concentrated under reduced
pressure. Chromatography (9:1, CHCl3–
MeOH containing 1% Et3N) of the syrup gave
the title compound in 44% yield [h]D 120° (c
2.04, CH3CH2OH). 13C NMR (CD3OD): l
104.1 (C-1), 80.9 (C-5), 79.3 (C-2), 78.5, 77.5
(C-3 and C-4), 61.8 (C-6), 58.4 (O-CH3), 56.1
1
(CH3), 56.0 (CH3). H NMR (D2O) l: 5.22 (1
H, m, H-4), 5.05 (2 H, m, H-1, H-3), 4.46 (1
H, d, H-5), 4.34 (1 H, s, H-2), 3.60 (3 H, s,
CH3), 3.31 (3 H, s, CH3). Anal. Calcd for
C8H12O6: C, 47.06; H: 5.92. Found C, 47.06;
H, 6.04.
Ethyl 5-O-methyl h- -glucofuranosidurono-
D
6,3-lactone (4).—BF3 etherate (1.5 mL) was
added to EtOH (10 mL) and 0.2 mL of this
solution was added to a solution of 5-O-
methyl a-
-glucono-6,3-lactone3 (2.0 g, 10.5
D
mmol) dissolved in triethyl orthoformiate (50
mL, dried over Drierite). The solution was
stirred for 2 h and neutralized with Et3N.
After standard work up the syrup was purified
by column chromatography (39:1, CHCl3–
MeOH). Two consecutive crystallizations
from toluene gave 4 in 26% yield. 13C NMR
(D2O) l: 175.6 (C-6), 103.9 (C-1), 86.6 (C-3),
77.9 (C-5), 75.9 (C-2), 74. 6 (C-4), 65.9 (CH2),
1
(O-CH3). H NMR (CD3OD): l 4.93 (1 H, d,
H-1), 4.12 (2 H, m, H-3 and H-4), 3.99 (1 H,
q, H-2), 3.88 (1 H, dd, H-6%), 3.63 (1 H, dd,
H-6), 3.50 (1 H, m, H-5), 3.46 (3 H, s, CH3),
3.43 (3 H, s, CH3). FAB-MAS Calcd for
C8H16O6 (M+Na) 231.0845. Found (M+
Na) 231.0835.
1
59.5 (CH3), 15.0 (CH3). H NMR (D2O) l:

K.-J. Johansson et al. / Carbohydrate Research 332 (2001) 33–39
39
Methyl
5-O-methyl-i-
D
-glucofuranoside
through Celite.8 The filtrate was concentrated
under reduced pressure. Chromatograph (9:1,
CHCl3–MeOH containing 1% Et3N) of the
resulting syrup gave the title compound in
76% yield. [h]D −84° (c 1.85, CH3CH2OH).
13C NMR (CD3OD) l: 109.5 (C-1), 81.8 (C-2
and C-4), 80.8 (C-5) 76.8 (C-3), 64.7 (CH2),
(7).—A solution of 3 (126 mg, 620 mmol) and
lithium aluminum hydride (53 mg, 1.4 mmol)
in freshly distilled THF (10 mL) was refluxed
for 1 h. The reaction was quenched with an
excess of Na2SO4·10 H2O and filtered through
Celite.8 The filtrate was concentrated under
reduced pressure. Chromatography (9:1,
CHCl3–MeOH containing 1% Et3N) of the
syrup gave the title compound in 72% yield.
[h]D −87° (c 2.35, CH3CH2OH). 13C NMR
(CD3OD): l 110.9 (C-1), 82.0 (C-4), 81.7 (C-
2), 80.8 (C-5), 76.7 (C-3) 62.1 (C-6), 58.3
1
62.1 (C-6), 58.3 (CH3), 15.5 (CH3). H NMR
(CD3OD) l: 4.84 (1 H, d, H-1), 4.14 (1 H, q,
H-4), 4.02 (1 H, d, H-3), 4.00 (1 H, s, H-2),
3.93 (1 H, dd, H-6%), 3.77–3.49 (4 H, m, H-5,
H-6 and CH2), 3.47 (3 H, s, CH3), 1.19 (3 H,
t, CH3). FAB-MS Calcd for C9H18O6 (M+H)
m/z 223.1182. Found (M+H) m/z 223.1167.
Kinetic runs.—The runs were performed in
Supelco screw cap vials with PTFE/Neopren
septa. Glassware were dried at 110 °C and
cooled in a desiccator. The glucosides were
dissolved in 1 mL of water and freeze-dried in
the vials. The vials with the glucoside (10 mg)
and the 0.6 M CSA in MeOH or EtOH (5
mL) were cooled in an ice-water bath before
to mixing. The reactions were performed at
0 °C. Aliquots (100 mL) were withdrawn with
a syringe at suitable intervals and neutralized
with DOWEX 1X4-200 resin (OH−). The so-
lutions were concentrated, acetylated, and an-
alyzed by GC and GC–MS. The components
were identified by comparison with authentic
substances or from their mass spectra. The
molar proportions of the components were
estimated from the areas under the GC peaks
and corrected by response factors.9
1
(OꢀCH3), 55.6 (OꢀCH3). H NMR (CD3OD):
l 4.74 (1 H, s, H-1), 4. 17 (1 H, dd, H-4), 4.03
(1 H, d, H-3), 4.00 (1 H, t, H-2), 3.95 (1 H,
dd, H-6%), 3.67 (1 H, dd, H-6), 3.57 (1 H, m,
H-5), 3.47 (3 H, s, CH3), 3.34 (3 H, s, CH3).
FAB-MS Calcd for C8H16O6 (M+Na) m/z
231.0845. Found (M+Na) m/z 231.0834.
Ethyl 5-O-methyl-h- -glucofuranoside (8).
D
—A solution of 4 (192 mg, 880 mmol) and
lithium aluminum hydride (37 mg, 970 mmol)
in freshly distilled THF (10 mL) was refluxed,
after 4 h an additional proportion of lithium
aluminum hydride (50 mg, 1.3 mmol) was
added. After further 30 min the reaction was
quenched with an excess of Na2SO4·10 H2O
and filtrated through Celite.8 The filtrate was
concentrated under reduced pressure and the
resulting syrup purified by column chro-
matograph (5:1, toluene–MeOH). Recrystal-
lization from EtOAc and hexane gave 8 in
38% yield. [h]D 104° (c 1.27, EtOH). 13C NMR
(D2O) l: 102.3 (C-1), 79.7 (C-5), 77.4 (C-4),
77.3 (C-2), 76.2 (C-3), 65.7 (CH2), 60.4 (C-6),
References
1
58.0 (CH3), 15.0 (CH3). H NMR (D2O) l:
5.14 (1 H, d, H-1), 4.24 (1 H, t, H-3), 4.17 (1
H, t, H-4), 4.10 (1 H, t, H-2), 3.91 (1 H, dd,
H-6%), 3.80 (1 H, m, CH2), 3.62 (2 H, m, H-6
and CH2), 3.52 (1 H, m, H-5), 3.42 (3 H, s,
CH3), 1.18 (3 H, t, CH3). Anal. Calcd for
C9H18O6: C, 48.64; H: 8.16. Found C, 48.79;
H, 8.28.
1. Capon, B.; Thacker, D. J. Chem. Soc. (B) 1967, 1322–
1326.
2. Kaczmarek, J.; Lo¨nnberg, H.; Szafranek, J.; Kenneth, C.
B. W. Finn. Chem. Lett. 1987, 14, 171–177.
3. Nakajima, H. Yakugaku Zasshi 1961, 81, 1094–1099.
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Chem. 1957, 22, 1513–1514.
5. Garegg, P.; Johansson, K.-J.; Lindberg, B.; Trumpakaj, Z.
Carbohydr. Res. 2001, submitted.
6. Garegg, P. J.; Johansson, K.-J.; Konradsson, P.; Lindberg,
B. J. Carbohydr. Chem. 1999, 18, 31–40.
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Wimalasiri, W. J. Org. Chem. 1991, 56, 3358–3362.
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Res. 1975, 40, 217–225.
Ethyl 5-O-methyl-i- -glucofuranoside (9).
D
—A solution of 5 (202 mg, 930 mmol) and
lithium aluminum hydride (88 mg, 2.3 mmol)
in freshly distilled THF (10 mL) was refluxed
for 1 h. The reaction was quenched with an
excess of Na2SO4·10 H2O and filtrated
.