Electroorganic synthesis 66: Selective anodic oxidation of carbohydrates mediated by TEMPO

Article abstract of DOI:10.1055/s-1999-3464

The carbohydrates 4-15 are anodically oxidized with 2,2,6,6- tetramethylpiperidin-1-oxyl (TEMPO) as mediator. Selective and complete reaction at the primary hydroxyl groups affords the corresponding carboxylic acids 16-32 in moderate to excellent yield. Methyl α-D-glucopyranoside is converted in 98% yield to the uronic acid 16. Cyclic voltammetry shows that the oxydation is base-catalyzed and the oxidation of the hydroxy group with TEMPO⁺ (2) is rate determining.

Full text of DOI:10.1055/s-1999-3464

864
PAPER
Electroorganic Synthesis 66:1 Selective Anodic Oxidation of Carbohydrates
Mediated by TEMPO
Karsten Schnatbaum, Hans J. Schäfer*
Organisch-Chemisches Institut der Universität Münster, Corrensstraße 40, D-48149 Münster, Germany
Fax +49(251)8339772; E-mail: schafeh@uni-muenster.de
Received 30 September 1998
Dedicated to Prof. Dr. B. Krebs on the occasion of his 60th birthday
Reactions with TEMPO and its derivatives are of industri-
Abstract: The carbohydrates 4–15 are anodically oxidized with
al interest. Substituted nitroxyl radicals are prepared in
2,2,6,6-tetramethylpiperidin-1-oxyl (TEMPO) as mediator. Selec-
tive and complete reaction at the primary hydroxyl groups affords
the corresponding carboxylic acids 16–32 in moderate to excellent
larger amounts in high yields starting from the inexpen-
sive basic chemicals acetone and ammonia.29 Additional-
yield. Methyl a-D-glucopyranoside is converted in 98% yield to the ly the mediator TEMPO can be easily recovered in
quantitative yield after the oxidation of polysaccharides.27
uronic acid 16. Cyclic voltammetry shows that the oxydation is
base-catalyzed and the oxidation of the hydroxy group with TEM-
Several oxidants have been applied for the continuous re-
generation of 2 in the oxidation of alcohols.10,30,31 Howev-
er, preparative oxidations of carbohydrates to uronic acids
were usually performed with sodium hypochlorite as re-
generating agent and TEMPO/NaBr as double mediatory
system. Under these conditions hypochlorite or the inter-
mediate bromine can cause side reactions with sensitive
functional groups and the separation of polar products
from concentrated aqueous solutions of sodium bromide
is difficult or often impossible.15
PO+ (2) is rate determining.
Key words: anodic oxidation, carbohydrates, TEMPO, cyclic vol-
tammetry, uronic acids
Introduction
The selective oxidation of carbohydrates has been inten-
sively studied in the last decades and continues to be an
area of timely interest.2–6 This holds especially for the
conversion to uronic acids. Direct oxidations with
stoichiometrically employed reagents like nitric acid7 and
nitrogen dioxide8 as well as catalytic methods, e.g. oxy-
gen with noble metal catalysts,4,6,9 have been applied.
In the following paper a method for the selective oxida-
tion of carbohydrates with electrochemically regenerated
2 is presented. The mediated electrochemical oxidation
has the advantage that the electrode does not interfere
with the alcohol oxidation and that the electrolysis is easy
to work up and to scale up. Thus far anodic oxidations of
carbohydrates to uronic acids with TEMPO as mediator
have been performed for analytical purposes only.12,32,33
Recently catalytic methods using stable organic nitroxyl
radicals like 2,2,6,6-tetramethylpiperidin-1-oxyl (TEM-
PO, 1) as mediator have been developed.10–28 The actual
oxidation reagent is the nitrosonium ion 2 which is ob-
tained by oxidation of 1 (Scheme 1). In the oxidation of
alcohols the nitrosonium ion 2 is reduced to the hydroxyl-
amine 3. At pH values higher than 3, the hydroxylamine 3
symproportionates with 2 to the radical 1.
Scheme 1
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Selective Anodic Oxidation of Carbohydrates Mediated by TEMPO
865
Cyclic Voltammetry
At first the mediated anodic oxidation of methyl a-D-glu-
copyranoside (4) with TEMPO as mediator was examined
by cyclic voltammetry. 2,2,6,6-Tetramethylpiperi-
din-1-oxyl (1) is oxidized chemically reversible
(Figure 1) with an anodic to cathodic peak current ratio of
1.0. This is an important requirement for a mediator, be-
cause it indicates that it can be completely recovered from
an oxidation-reduction cycle.
Figure 2 Cyclic voltammogram of TEMPO (0.009 mol/L) with (so-
lid line) and without (dashed line) methyl a-D-glucopyranoside (4)
(0.1 mol/L) in water (0.2 mol/L NaClO4, Na2CO3 buffer, pH 10, 10
mV/s)
catalytic efficiency is the ratio of catalytic current to dif-
fusion current of TEMPO alone. This indicates that the
anodic oxidation of 4 catalyzed by TEMPO is base cata-
lyzed. This finding supports the mechanism for the oxida-
tion of alcohols with 2 under basic conditions as proposed
by van Bekkum et al.10,17 (Scheme 2). The alcohol first
adds to the nitroso group of 2. Subsequent deprotonation
of the OH group and intramolecular β-elimination affords
the hydroxylamine 3 and the aldehyde, whose hydrate is
further oxidized to the corresponding carboxylic acid.
Figure 1 Cyclic voltammogram of TEMPO (0.009 mol/L) in water
(0.2 mol/L NaClO4, Na2CO3 buffer, pH 10, 10 mV/s)
Figure 2 shows cyclic voltammograms of 9 mmol/L
TEMPO and 100 mmol/L methyl a-D-glucopyranoside
(4). Compared to pure TEMPO, the oxidation peak in-
creased significantly at slow scan rates and the reduction
peak disappeared (Figure 2). This is the typical behaviour
for a mediator assisted oxidation and indicates that the
oxydized form of TEMPO reacts with the alcohol and
therefore cannot be reduced in the second part of the cy-
cle. Additionally the catalytic effect of TEMPO is shown
by the fact that methyl a-D-glucopyranoside (4) alone is
not oxidized at potentials less than 1.0 V.
In contrast to the behaviour of TEMPO and methyl
α
D-glucopyranoside (4) at low scan rates, no catalytic
Figure 3 Catalytic efficiency [ipa (TEMPO + substrate)] of the Tem-
po-catalyzed oxidation of 4 versus pH (0.009 mol/L TEMPO, 0.1
mol/L 4, 0.2 mol/L NaClO4, phosphate or carbonate buffer, pH 7–11,
10 mV/s)
reaction was observed at high scan rates. This indicates
that the reaction of oxidized TEMPO with 4 is slow com-
pared with the scan rate and the anodic oxidation of TEM-
PO.
Figure 3 shows a significant increase of the catalytic effi-
ciency of the mediator with the pH of the solution. The
Scheme 2
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K. Schnatbaum, H. J. Schäfer
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Table 1 TEMPO Mediated Anodic Oxidation of Monosaccharides
Entry
1
Substratea
Product
Yield [%]
96b (98c)
2
3
4
5
6
96b
59b
45b,d
63b
89b
7
8
52e
45f
a Conditions as described in the experimental section.
b Isolated as methyl ester.
c Determined by calibrated GC with tetradecanoic acid methyl ester as internal standard.
d 12% of 7 was recovered.
e Isolated as trisodium salt.
f Isolated as dimethyl ester.
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Selective Anodic Oxidation of Carbohydrates Mediated by TEMPO
867
tants.35,36 By electrochemical oxidation the carboxylic
Preparative Scale Electrolyses of 4–15
acids 20 and 21 were obtained in good yields of 63 and
As the results of cyclic voltammetry looked promising, 89%, respectively (Table 1, Entries 5 and 6). With TEM-
methyl a-D-glucopyranoside (4) and the monosaccharides PO/NaBr as a double mediatory system and NaOCl as
5–11 were oxidized in a preparative scale (Table 1). In chemical oxidant in a two phase system 8 was oxidized to
general 20 mol% (9–16 wt%) of TEMPO were used at 20 in 67% yield.13
conditions described in the experimental section.
a-D-Glucopyranoside 1-disodiumphosphate (10) is oxi-
In all substrates the primary hydroxyl group is oxidized to dized to the corresponding uronic acid 22 in 52% yield
the carboxylic acid. The selectivity of primary versus sec- (Table 1, Entry 7). As 10 is easily obtained from starch
ondary alcohol oxidation and of carboxylic acid versus al- and 22 can be hydrolyzed to glucuronic acid in good
dehyde formation is in general high, which also holds for yields, the reaction might be an interesting key step in the
the product yield.
production of glucuronic acid from starch.37 In this con-
text it is important to note that the synthesis of D-glucu-
ronic acid by acid hydrolysis of polyglucuronic acid
proceeds slowly and leads to undesired side products.38
Glucuronic acid is an interesting intermediate for fine
chemicals like L-ascorbic acid or D-glucaric acid.3
Methyl a-D-glucopyranoside (4) is oxidized rapidly to the
corresponding uronic acid 16 (Table 1, Entry 1) in a yield
of 98% (calibrated GC) or 96% (isolated as methyl ester).
No side product could be detected by GC analysis or
NMR spectroscopy. The oxidation of 4 described here
gave the highest yield of the product reported so far to our By anodic oxidation with TEMPO as mediator, D-(–)-sali-
knowledge (except in one publication, however, without cin (11), a natural compound occuring up to 7% in the
experimental details).34 The oxidation of 4 with TEMPO bark of willow-trees and poplars, is converted to the dicar-
and NaOCl/NaBr as chemical oxidant has been described, boxylic acid 23 in a moderate yield of 45% (Table 1, En-
but 4 is not isolated in these cases.15–18 After the reaction, try 8).
the mediator TEMPO could be very easily recovered in
78% yield by extraction of the aqueous solution with di-
ethyl ether. Taking into consideration that TEMPO is
quite volatile, this recovery is very good.
Besides monosaccharides the di-, oligo- and polysaccha-
rides 12–15 were also converted to the corresponding car-
boxylic acids in good to moderate yields (Table 2). From
a,a-trehalose (12) the dicarboxylic acid 24 was obtained
Besides the use of TEMPO as mediator methyl a-D-glu- in 61% yield (Table 2, Entry 1). The high selectivity is re-
copyranoside (4) was electrolyzed with 4-acetami- markable considering that no reaction at the six secondary
do-TEMPO10 under the same conditions. As the product hydroxyl groups is detectable. Compound 24 is a key in-
uronic acid was isolated in 95% yield as its methyl ester termediate for the synthesis of glycolipids with antitumor
after methylation, the substituent in the 4-position of the properties.39
mediator seems to have no effect on the selectivity of the
carbohydrate oxidation. However, the oxidation with
Sucrose (13) contains three primary hydroxyl groups that
should be oxidizable with TEMPO as mediator. Results
TEMPO appears more favourable because only 20% of
with oxygen over platinum as oxidant34,40–43 showed that
the 4-acetamido-TEMPO could be recovered. Probably
the 6- and the 6’-OH function are easier oxidized than the
1-hydroxyl group. The same result was obtained with
electrochemically regenerated 2. In an electrolysis with
the 4-acetamido-TEMPO is partially decomposed by oxi-
dation at the acetamido group.
Methyl β-D-glucopyranoside (5) is converted to uronic 4.8 F/mol consumption of charge (the oxidation of a pri-
acid 17 in a yield of 96% indicating that the configuration mary OH group to a carboxylic acid needs 4.0 F/mol) the
at the anomeric center does not influence the selectivity of monocarboxylic acids 25, 26 and 27 were formed in a ra-
the C-6-oxidation (Table 1, Entry 2). The reaction rate is tio of 17:40:43 with a total yield of 22% (determined by
slightly lower than the one observed for methyl a-D-glu- GC, 27% based on conversion of 83% of sucrose, Table 2,
copyranoside (4). With chemically regenerated 2 in a two Entry 2). As side products, 14% of glucaric acid and
phase system a yield of only 55% is obtained.13
smaller amounts of other monosaccharide acids were
found which indicates that the low yield for the sucrose
monocarboxylic acids is mainly due to disaccharide
cleavage. Experiments directed towards the increase of
the selectivity of formation of 25, 26 and 27 by means of
Methyl a-D-galactopyranoside (6) and methyl a-D-man-
nopyranoside (7) are oxidized in good to moderate yields
to the corresponding uronic acids (Table 1, Entries 3 and
4). The lower selectivity compared with the oxidation of
methyl a-D-glucopyranoside (4) is probably due to the
equatorial CH-bonds (at C-4 in 6 or at C-2 in 7) that are
accessible easier than the axial ones and therefore can be
extraction
of
formed
carboxylic
acids
by
electrodialysis34,42,43 did not lead to higher yields of su-
crose monocarboxylic acids.
attacked more easily. This leads to ketones as undesired Sucrose tricarboxylic acid (28) is interesting as complex-
side products that can undergo base catalyzed reactions.
ing agent, food additive and starting compound for the
preparation of fine chemicals.43,44 Nevertheless, the yield
for the oxidation of 13 to 28 is reported only once. By plat-
inum-catalyzed oxidation of 13 with oxygen 29% of 28
was obtained as determined by uncalibrated GC analy-
Carbohydrates 8 and 9 are nonionic surfactants from the
class of alkyl polyglucosides. The conversion of these
compounds into the carboxylic acids allows the transfor-
mation of nonionic surfactants into anionic surfac-
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K. Schnatbaum, H. J. Schäfer
PAPER
sis.44 In order to prepare sucrose tricarboxylic acid (28) mediator (Table 2, Entry 4). ESI/MS and NMR analyses
with TEMPO as mediator sucrose (13) was electrolyzed showed less than 10% side products from nonselective
until a charge of 19.7 F/mol was consumed. Compound oxydations. The carboxylic acid groups in 29–31 can pos-
28 was obtained in 39% yield (isolated as nonahydrate of sibly be used to covalently attach (immobilize) the cyclo-
the trisodium salt, Table 2, Entry 3). Although the yield of dextrin at a support. Otherwise selective oxidations with
28 is only moderate, this is a significant improvement β-cyclodextrin are rare.7,16,46–49 The diuronic acid is acces-
compared to the yield described before. The reaction sible, however in only 14% yield, by a two step oxidation
could be of industrial interest as sucrose is the most abun- sequence starting from the ditosylate of β-cyclodextrin.46
dant and highly pure organic compound of low molecular The oxidation of β-cyclodextrin with NaOCl, NaBr and
weight available commercially.45
TEMPO is reported in a patent,16 however details on the
product are not described.
β-Cyclodextrin (14) was converted to a mixture of tri-, tet-
ra- and pentauronic acids 29, 30 and 31 in a ratio of about Potato starch (15) is very selectively oxidized at the pri-
1:2:1 in 74% yield by anodic oxidation with TEMPO as mary hydroxyl groups in 6-position. After electrolysis
Table 2 TEMPO Mediated Anodic Oxidation of Di-, Oligo- and Polysaccharides
Entry
Substratea
Product
Yield (%)
1
61b
2
3
4
22c
39d
74e
5
63f
a Conditions as described in the experimental section.
b Isolated as dimethyl ester.
c Determined by calibrated GC with methyl a D-galactopyranoside as internal standard, 27% based on conversion of 83% of starting material,
ratio 25:26:27 = 17:40:43 determined by HPLC.
d Isolated as trisodium salt.
e Obtained as crude product (113%) containing H2O (27%) and minor side products (<10%, determined by NMR and ESI-MS), ratio 1:2:1
(determined by ESI-MS).
f Obtained as crude product as sodium salt (70%) containing less than 10% of side products (determined by NMR), 93% carboxylate content
(measured by NMR).
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Selective Anodic Oxidation of Carbohydrates Mediated by TEMPO
869
For the isolation and characterization of the reaction products the
carboxylic acids were usually converted into their methyl esters as
follows. A part of the crude product was dissolved in MeOH
(10 mL) and treated with 2,2-dimethoxypropane (1.0 mL,
8.2 mmol) and one drop of concd aq HCl (p.A.). After stirring for
1 d, the solvent was removed under reduced pressure and the crude
product purified by flash chromatography on silica gel.
with TEMPO as mediator 63% of the corresponding poly-
uronic acid was isolated as crude product with a 93% con-
version of the primary alcohol groups (determined by
NMR, Table 2, Entry 5). van Bekkum et al.15,16,18 describe
a selectivity of >95% and a crude product yield of 98% for
the reaction with chemically (NaOCl, NaBr) regenerated
2. The electrochemical method leads to slightly lower
yields but has the advantage that sodium bromide which
is used in the chemical reaction in high concentration
(49 mol%) is avoided.
Methyl (Methyl a-D-glucopyranosid)uronate (Methyl Ester of
16)
Electrolysis with TEMPO: Methyl α D-glucopyranoside (4,
970 mg, 5.00 mmol) and TEMPO (156 mg, 1.00 mmol) were elec-
trolyzed according to the general procedure. After a consumption of
2660 C (5.5 F/mol) the electrolysis was stopped and the solution
was extracted with EtOAc (3 î 50 mL). The combined organic
layers were dried (MgSO4) and the solvent removed in vacuo. Flash
Conclusion
Anodic oxidation with 2,2,6,6-tetramethylpiperidin-1-ox- chromatographic purification (petroleum ether/Et2O, 5:1) afforded
TEMPO (122 mg, 0.78 mmol, 78%). The aqueous layer was
worked up as described in the general procedure. This afforded
1.12 g of crude product, a part of which (229 mg) was esterified. By
flash chromatographic purification (silica gel, EtOAc/MeOH, 3:1)
yl (TEMPO, 1) as mediator converts primary hydroxyl
groups in polyols selectively to the corresponding carbox-
ylates. Secondary OH-groups are in most cases inert
against oxidation. This selectivity allows the chemoselec-
tive oxidation of carbohydrates 4–15 into the correspond-
ing carboxylic acids 16–32, which are isolated in
moderate to excellent yield. The electrochemical oxida-
16 (219 mg, 0.99 mmol, 96%) was isolated as a colourless oil.
Electrolysis with 4-Acetamido-TEMPO: According to the general
procedure, methyl a-D-glucopyranoside (4; 970 mg, 5.00 mmol)
was electrolyzed with 4-acetamido-TEMPO (213 mg, 1.00 mmol)
tion with TEMPO as mediator can favorably compete
with respect to yield, chemoselectivity and workup with
alternative oxidations, e.g. with oxygen at a platinum cat-
alyst or sodium hypochlorite combined with TEMPO.
until a consumption of 2740 C (5.7 F/mol). The solution was ex-
tracted three times with Et2O (100 mL). After drying the combined
organic layers (MgSO4) and subsequent removal of the solvent in
vacuo 4-acetamido-TEMPO (42 mg, 0.20 mmol, 20%) was recov-
ered. The aqueous layer was worked up according to the general
procedure to give the crude product (1.22 g), a part of which (201
mg) was esterified. Subsequent isolation of the methyl ester of 16
(173 mg, 0.78 mmol, 95%) was achieved by flash chromatography
(silica gel, EtOAc/MeOH, 3:1). The spectroscopic data were in ac-
cordance with the literature values.50
All chemicals are commercially available and used without further
purification; dodecyl α,β-D-glucopyranoside from Henkel AG,
Düsseldorf, Germany, was purified by flash chromatography on sil-
ica gel (EtOHc/MeOH, 10:1). IR spectra were obtained with a
Bruker IFS 28 FT-IR-spectrometer. NMR spectra were recorded on
1
a Bruker spectrometer WM 300 (300 MHz and 75.4 MHz, for H
Methyl (Methyl b-D-glucopyranosid)uronate (Methyl Ester of
17)
and 13C, respectively; D2O, CDCl3 as solvent). The measurement of
GC/MS spectra was conducted on a Finnigan-MAT 312 (70 eV)
with a capillary column HP 5 (25 m, 0.2 mm i.d., 0.33 mm film). For
DCI ammonia served as reactant gas. ESI mass spectra were record-
ed on a micromass quadrupole mass spectrometer Quattro LC-Z.
Gas chromatography was carried out on a Hewlett-Packard
HP 5890 Series II with the capillary columns HP 1 (25 m, 0.32 mm
i.d., 0.3 µm film) and HP 5 (25 m, 0.20 mm i.d., 0.52 µm film). El-
emental analyses were conducted by the analytical laboratory of Or-
ganisch-Chemisches Institut der Universität Münster. For cyclic
voltammetry the Metrohm/Eco Autolab System PG STAT 20 and
Metrohm VA-Stand 663 V were used with a glassy carbon disc an-
ode (3 mm diameter) and a glassy carbon rod cathode. The refer-
ence electrode was Ag/AgCl/3 M KCl in H2O (+0.21 V vs. NHE).
Preparative scale electrolyses were carried out in undivided beaker-
type glass cells (capacity 60, 100 or 200 mL) with a platinum foil
anode (18 cm2) on a teflon frame and a graphite cathode (24 cm2,
electrographite, Sigri). As reference electrode served a saturated
calomel electrode (Hg/Hg2Cl2/saturated KCl in H2O, +0.20 V vs.
SCE). The applied current source was a Wenking HP 88.
Methyl b-D-glucopyranoside hemihydrate (1.015 g, 5.00 mmol)
and TEMPO (156 mg, 1.00 mmol) were dissolved in carbonate
buffered water (100 mL) and electrolyzed according to the general
procedure until 2895 C (6.0 F/mol) were consumed. Workup af-
forded 1.19 g of crude product, from which 193 mg was esterified
to the methyl ester of 17 (173 mg, 0.78 mmol, 96%), which was iso-
lated by flash chromatography (silica gel, EtOAc/MeOH, 3:1) as a
colourless oil.The spectroscopic data corresponded to those in the
literature.13
Methyl (Methyl a-D-galactopyranosid)uronate (Methyl Ester of
18)
Methyl a-D-galactopyranoside (6; 974 mg, 5.02 mmol) and TEM-
PO (156 mg, 1.00 mmol) were electrolyzed according to the general
procedure. After consumption of 2900 C (6.0 F/mol) the electroly-
sis was stopped and worked up. 1.07 g of crude product was ob-
tained from which 485 mg was esterified. By flash chromatographic
purification (silica gel, EtOAc/MeOH, 3:1) the methyl ester of 18
(300 mg, 1.35 mmol, 59%) was isolated as a white solid, mp 148–
149 °C. The spectroscopic data corresponded to those in the litera-
ture.51
General Procedure for the Electrolyses
The given amounts of the carbohydrate and 2,2,6,6-tetramethylpip-
eridin-1-oxyl (TEMPO) were dissolved in carbonate buffered water
(100 mL of 42.80 g/L, 0.40 mol/L Na2CO3, 24.80 g/L, 0.30 mol/L
NaHCO3). The solution was electrolyzed at 20 °C at a potential of
0.53 V versus SCE. After the electrolysis a strongly acidic cation-
exchange resin (93 mL, 49 mequiv of Amberlite IR 120) was added
and after stirring for 0.5 h the resin was filtered off and the solvent
removed at 50 °C in vacuo.
Methyl (Methyl a-D-mannopyranosid)uronate (Methyl Ester of
19)
According to the general procedure methyl α-D-mannopyranoside
(7; 972 mg, 5.01 mmol) was electrolyzed with TEMPO (156 mg,
1.00 mmol) until 3540 C (7.3 F/mol) of charge were consumed. A
part (499 mg) of the crude product (1.07 g) was esterified. This pro-
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K. Schnatbaum, H. J. Schäfer
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cedure had to be conducted twice to achieve total conversion. Sub-
sequent isolation of the ester by flash chromatography (EtOAc/
MeOH, 3:1) afforded the methyl ester of 19 (234 mg, 1.05 mmol,
45%) as a pale yellow oil besides the starting material 7 (53 mg,
0.27 mmol, 12%). The spectroscopic data of the methyl ester of 19
were in accordance with those in the literature.50
(4.7 F/mol) was consumed, worked up according to the general pro-
cedure with cation-exchange resin (110 mL). The obtained aqueous
solution was not evaporated in vacuo and methylated, but 0.5 M aq
KOH was added until a pH of 7 was reached. The solution was con-
centrated in vacuo to 6 mL and the product precipitated by dropwise
addition of MeOH (28 mL). The precipitate was filtered off and re-
crystallized in H2O/MeOH (113 mL, 8:3). The tetrahydrate of the
tripotassium salt of 22 (1.20 g, 2.61 mmol, 52%) was obtained as a
white solid, mp 191–193 °C (dec). The 1H NMR spectroscopic data
corresponded to those in the literature for the sodium potassium salt
of 22.37
Methyl (Octyl b-D-glucopyranosid)uronate (Methyl Ester of 20)
Octyl b-D-glucopyranoside (8; 488 mg, 1.67 mmol) and TEMPO
(52 mg, 0.33 mmol) were electrolyzed according to the general pro-
cedure with the following deviation: only 33 mL of electrolyte were
used instead of 100 mL and the area of the electrodes was halved.
After a consumption of 714 C (4.4 F/mol), the electrolysis was
stopped and worked up. In this case the solution was not treated
with an acidic cation-exchange resin but acidified with 2 M aq HCl
until pH 1 and continuously extracted with Et2O (600 mL) for 2 d.
The organic layer was dried (MgSO4) and the solvent evaporated in
vacuo. 472 mg of crude product was obtained from which 119 mg
was esterified. By flash chromatography (EtOAc/MeOH, 40:1) the
methyl ester of 20 (85 mg, 0.27 mmol, 63%) was isolated as white
solid, mp 50–52 °C. Additionally the starting material 8 (6 mg,
0.02 mmol, 5%) was recovered. The spectroscopic data of the me-
thyl ester of 20 corresponded to those in the literature.13
Anal. C6H16K3O14P (460.5): calcd C 15.65, H 3.50; found C 15.57,
H 3.44.
Methyl (2-Methoxycarbonyl-phenyl b-D-glucopyranosid)ur-
onate (Dimethyl Ester of 23)
D-(–)-Salicin (11; 716 mg, 2.50 mmol) and TEMPO (78 mg,
0.50 mmol) were electrolyzed according to the general procedure.
After a consumption of 2700 C (11.2 F/mol) the electrolysis was
worked up. 808 mg of crude product was obtained from which
209 mg was esterified. The dimethyl ester of 23 (67 mg, 0.20 mmol,
30%) and a portion of only partially methylated diacids were isolat-
ed by flash chromatography (EtOAc/MeOH, 6:1). The latter was
subjected repeatedly to the methylation procedure and the product
was purified by flash chromatography (EtOAc/MeOH, 10:1) which
afforded an additional amount of the dimethyl ester of 23 (32 mg,
0.09 mmol, 15%) as a colourless oil.
Methyl (Dodecyl D-glucopyranosid)uronate (Methyl Ester of
21)
According to the general procedure dodecyl D-glucopyranoside (9;
344 mg, 0.99 mmol, a/b = 80:20 determined by GC) were electro-
lyzed with TEMPO (32 mg, 0.20 mmol). The same deviations in the
general procedure as in the oxidation of 8 were applied. At first a
pale yellow suspension was formed which cleared up in the course
of the electrolysis. After a consumption of 672 C (6.7 F/mol) the
electrolysis was stopped. For workup the solution was not treated
with an acidic cation-exchange resin but acidified with 2 M aq HCl
until pH 1 and continuously extracted with Et2O (600 mL) for 3 d.
After drying of the organic layer (MgSO4) and evaporation of the
solvent in vacuo 186 mg of the 379 mg of crude product were ester-
ified. Product 21 (166 mg, 0.44 mmol, 91%) was isolated as a co-
lourless oil by flash chromatography (EtOAc).
IR (film): n = 3411 (s, OH), 1731 (m, C=O), 1713 (s, C=O), 1602
(m, C=C), 1491 cm–1(m, C=C).
1H NMR (D2O): d = 3.56–3.89 (m, 9 H, 2-H, 3-H, 4-H, 2 OCH3),
4.14 (d, 3J4, 5 = 9.3 Hz, 1 H, 5-H), 5.10 (d, 3J1, 2 = 7.4 Hz, 1 H, 1-H),
3
3
7.11 (dd, J4’, 5’ = 8.0 Hz, J5’, 6’ = 7.8 Hz, 1 H, 5’-H), 7.20 (d,
3J3’, 4’ = 8.6 Hz, 1 H, 3’-H), 7.48 (ddd, 3J3’, 4’ = 8.6 Hz,
3J4’, 5’ = 8.0 Hz, 4J4’, 6’ = 1.8 Hz, 1 H, 4’-H), 7.66 (dd,
4J4’, 6’ = 1.8 Hz, 3J5’, 6’ = 7.8 Hz, 1 H, 6’-H).
13C NMR (D2O): d = 52.3, 52.6 (2 q, 2 OCH3), 70.5, 72.1, 74.2, 74.5
(4 d, C-2, C-3, C-4, C-5), 100.6 (d, C-1), 116.8, 123.0, 130.6, 133.9
(4 d, 4 CHarom.), 120.9 (s, OCarom.), 154.8 (s, H3CO2C–Carom.), 168.0
(s, H3CO2C–Carom.), 169.9 (s, OCHCO2CH3).
IR (KBr): n = 3470 (s, OH), 1738 cm–1 (s, C=O).
1H NMR (DMSO-d6): d = 0.85 (t, 3J = 6.6 Hz, 3 H, CH2CH3), 1.15–
1.38 [m, 18 H, (CH2)9CH3], 1.43–1.59 (m, 2 H, OCH2CH2), 3.12–
3.47, 3.49–3.74 (2 m, 6 H, OCH2CH2, 2-H, 3-H, 4-H, OH), 3.64 (s,
3 H, OCH3), 3.71 (d, 3J = 9.8 Hz, 0.20 H, 5-Hβ), 3.88 (d,
3J = 9.5 Hz, 0.80 H, 5-Hα), 4.22 (d, 3J = 7.6 Hz, 0.20 H, 1-Hb), 4.67
(d, 3J = 3.8 Hz, 0.80 H, 1-Hα), 4.68, 4.84, 5.01, 5.19 (4 d, br, 2 H,
2 OH).
MS (70 eV): m/z (%) = 543 (M+ – CH3, 2), 437 [M+ – OCH3 –
Si(CH3)3OH, 1], 407 (4), 379 (2), 317 (60), 275 (10), 217
+
[(CH3)3SiOCHCHCHOSi(CH3)3 ,
16],
209
(29),
147
+
+
[(CH3)3SiOSi(CH3)2 , 16], 73 [Si(CH3)3 , 100].
HRMS (NH3, DCI): m/z calcd. for C15H18O9 + NH4, 360.1295;
found 360.1277.
13C NMR (DMSO-d6): d = 14.0 (q, CH2CH3), 22.2, 25.7, 28.8, 29.0,
29.1, 29.1, 29.2, 29.2, 29.4, 31.4 [10 t, (CH2)10CH3], 51.9 (q,
COOCH3), 67.8, 69.1 (2 t, OCH2CH2, a and b), 71.6, 71.6, 71.8,
71.9, 72.8, 73.2, 75.6, 76.0 (8 d, C-2, C-3, C-4, C-5, a and b), 99.5,
103.4 (2 d, C-1, a and b), 170.0, 170.1 (2 s, CO2CH3, a and b).
(Methyl a-D-glucopyranosyluronate) (Methyl a-D-glucopyrano-
siduronate) (Dimethyl Ester of 24)
According to the general procedure α,α-trehalose (12; 856 mg,
2.50 mmol) was electrolyzed with TEMPO (78 mg, 0.50 mmol) un-
til a consumption of 2120 C (8.8 F/mol) was reached. After the
electrolysis the mixture was worked up with cation-exchange resin
(129 mL). A part (302 mg) of the obtained of crude product 1.03 g)
was esterified. Subsequent isolation of the hemihydrate of the dim-
ethyl ester of 24 (181 mg, 0.44 mmol, 61%) was conducted by flash
chromatography (EtOAc/MeOH, 3:1). The spectroscopic data were
in accordance with those in the literature.39
MS (70 eV): m/z (%) = 577 (M+ – CH3, 3), 487 [M+ – CH3
–
Si(CH3)3OH, 1], 401 (5), 313 [(CH3)3SiOCHCHCHOC12H25+, 15],
+
247 (14), 234 (32), 217 [(CH3)3SiOCHCHCHOSi(CH3)3 , 100],
+
+
204 [(CH3)3SiOCHCHOSi(CH3)3 , 84], 147 [(CH3)3SiOSi(CH3)2 ,
+
17], 73 [Si(CH3)3 , 57].
HRMS (NH3, DCI): m/z calcd. for C19H36O7 + NH4, 394.2805;
found, 394.2833.
a-D-Glucopyranosyl b-D-arabino-2-hexulofuranosidonic Acid
(25), a-D-glucopyranosyl b-D-fructofuranosiduronic Acid (26)
and b-D-fructofuranosyl a-D-glucopyranosiduronic Acid (27)
Potassium a-D-glucopyranosiduronate 1-(Dipotassium Phos-
phate) (Tripotassium Salt of 22)
a-D-Glucopyranoside-1-(disodium phosphate)monohydrate (1.52
g, 5.00 mmol) and TEMPO (156 mg, 1.00 mmol) were electrolyzed
in carbonate buffered water (100 mL) and, after a charge of 2245 C
Sucrose (13; 5.13 g, 15.0 mmol) and TEMPO (469 mg, 3.0 mmol)
were dissolved in a mixture of carbonate buffered water (100 mL)
and water (100 mL), and electrolyzed according to the general pro-
cedure. After a consumption of charge of 6970 C (4.8 F/mol) the
Synthesis 1999, No. 5, 864–872 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Selective Anodic Oxidation of Carbohydrates Mediated by TEMPO
871
electrolysis was stopped. The yields of sucrose monocarboxylic ac-
ids were determined by GC after silylation with N,O-bis(trimethyl-
silyl)acetamide (BSA) and Me3SiCl (TMSCl). Methyl α-
D-galactopyranoside was used as internal standard. Reference com-
pounds for the calibration of 25–27 were prepared according to the
literature.34,41,42 Sucrose (13; 17%), C-6-sucrose monocarboxylic
acid (26, 10%) and C-6’-sucrose monocarboxylic acid (27; 12%)
were isolated. The yield of 25 was too small to be detectable. The
ratio of 25, 26 and 27 was measured by calibrated HPLC as
17:40:43.52 Products 25–27 were characterized by mass spectrome-
try. The spectra of the silylated compounds were in accordance with
those in the literature.53
[(M(29) – H)–, 12], 803.0 [(2 M(31) – 3H)3–, 14], 797.5 [(2 M(30) –
3H)3–, 22], 792.8 [(2 M(29) – 3H)3–, 30], 601.8 [(M(31) – 2H)2–,
57], 594.5 [(M(30) – 2H)2–, 100], 587.6 [(M(29) – 2H)2–, 46], 544.9
(25), 536.4 (19).
Sodium (1→4)-a-D-glucuronan (Sodium Salt of 32)
Soluble potato starch (15; 812 mg, 5.00 mmol of glucose units) was
to a major part dissolved, a minor part formed a suspension in boil-
ing water (100 mL) and was electrolyzed at 20 °C according to the
general procedure with TEMPO (156 mg, 1.00 mmol), Na2CO3
(4.28 g, 40.4 mmol) and NaHCO3 (2.48 g, 29.5 mmol). After
3326 C (6.9 F/mol per glucose unit) were consumed, 25 mL of the
solution were diluted with H2O (6 mL), filtered and neutralized with
1 M aq HCl. Subsequently, the product was precipitated by drop-
wise addition of EtOH (490 mL) and filtered. The white solid was
dissolved in H2O (10 mL) and the solution extracted with Et2O (2 î
10 mL). After removal of water in vacuo the sodium salt of 32 was
obtained as crude product (80 mg, 70%) containing less than 10%
of side products (determined by NMR) as a white solid, mp 245–
247 °C (dec).
(Sodium a-D-glucopyranosyluronate) (Disodium b-D-arabi-
no-2-hexulofuranarat) (Trisodium Salt of 28)
According to the general procedure sucrose (13; 5.13 g, 15.0 mmol)
was electrolyzed with TEMPO (469 mg, 3.0 mmol). Deviating
from the general procedure a mixture of aq Na2CO3 buffered solu-
tion (100 mL) and water (100 mL) was used as electrolyte. TEMPO
was added in five portions of 77 mg (0.49 mmol) in equal time in-
tervals during the electrolysis. After a consumption of 28450 C
(19.7 F/mol) the electrolyte was treated with strongly acidic cation-
exchange resin (184 mL). The resin was filtered off and the free car-
boxylic acid was converted into the sodium salt with 2 M aq NaOH
which was added until a pH of 8.6 was reached. Evaporation of the
solvent afforded 8.75 g of crude product from which 1.28 g was
suspended in H2O (4.5 mL), and the residue was filtered off. The
polar reaction products were precipitated by dropwise addition of
MeOH (20 mL), filtered, washed with MeOH/H2O (3 mL, 3:1) and
dried in vacuo. The procedure of dissolving in H2O (3 mL) and re-
precipitation with MeOH/H2O (3:1, 13 mL) was repeated four
times. The nonahydrate of the trisodium salt of 28 (523 mg,
0.85 mmol, 39%) was isolated as a white solid. The spectroscopic
data of the trisodium salt of 28 corresponded to those in the litera-
ture.44
The carboxylate content of 32 was measured by NMR spectrosco-
py, by integrating the peak of 1-H. The chemical shift of 1-H in the
case of ‘hydroxymethylcarboxylate’ 32a was found to be 5.04 ppm
and for the ‘dicarboxylate’ 32 5.44ppm (see also the 1H NMR val-
ues given below). A signal for the ‘diol’ 32b was not observed.
From the integrated value of 0.13 H-atoms for the signal of 1-H in
‘hydroxymethylcarboxylate’, a hydroxymethyl content of 13%/2 =
7% was calculated. This gives a carboxylate content of 93% for 32.
Tris(5-dehydroxymethyl-5-carboxy)cyclomaltoheptaose (29),
Tetrakis(5-dehydroxymethyl-5-carboxy)cyclomaltoheptaose
(30) and Pentakis(5-dehydroxymethyl-5-carboxy)cyclomalto-
heptaose (31)
b-Cyclodextrin (14; 1.27 g, 0.99 mmol) containing water (11.5%)
and TEMPO (219 mg, 1.40 mmol) were suspended in an aqueous
carbonate buffered solution (100 mL) and electrolyzed according to
the general procedure until 3725 C (39.0 F/mol) were consumed.
After the electrolysis, the clear solution was extracted with Et2O (2
î 25 mL) and subsequently worked up in accordance to the general
procedure. A mixture of 29, 30 and 31 was obtained as crude prod-
uct (1.33 g, 113%) containing water (27%) and minor side products
(<10%, determined by NMR and ESI-MS) as pale yellow crystals,
mp 180–182 °C (dec). The ratio of 29:30:31 was 1:2:1 (determined
by ESI-MS).
IR (KBr): n = 3427 (s, OH), 1618 cm–1 (s, C=O).
1H NMR (D2O): d = 3.16–4.27 (m, 4.13 H, 2-H, 3-H, 4-H, 5-H,
3
3
6-H), 5.04 (d, 0.13 H, J = 3.8 Hz), 5.44 (d, 0.87 H, J = 3.8 Hz).
13C NMR (D2O): δ = 57.1 (t, CH2OH), 71.3 (d, C-2), 71.8 (d, C-5),
72.5 (d, C-3), 75.4 (d, C-4), 96.5 (d, C-1), 175.5 (s, C-6).
The spectroscopic data were in accordance with values from the
literature15,16,18 except for a few minor peaks assigned to unreacted
primary alcohol groups.
IR (KBr): n = 3416 (s, OH), 1737 (s, C=O), 1033 cm–1 (s, CO).
1H NMR (D2O): d = 3.49–3.96 (m, 4.29 H, 2-H, 3-H, 4-H,
0.43 CHCH2OH, 0.43 CH2OH), 4.14–4.27 (m, 0.57 H, CHCO2H),
4.99–5.44 (m, 1 H, 1-H).
13C NMR (D2O): d = 59.0, 59.1, 59.6 (3t, 3 CH2OH), 70.2, 70.2,
70.5, 70.5, 70.5, 70.7, 70.7, 70.7, 70.8, 71.0, 71.0, 71.0, 71.0, 71.1,
71.1, 71.1, 71.2, 71.6, 71.7, 71.9, 71.9, 72.2, 72.2, 72.2, 72.2, 72.3,
72.6, 72.6 (28d, 7 C-2, 7 C-3, 7 C-4, 7 C-5), 99.0, 99.0, 99.1 (3 d,
3 HOCH2CHOCH), 101.2, 101.2, 101.2, 101.3 (4 d,
3 HO2CCHOCH), 171.4, 171.6, 172.0, 172.5 (4 s, 4 CO2H).
Acknowledgement
The work was supported through the Arbeitsgemeinschaft Industri-
eller Forschungsvereinigungen (AIF-Project No. 10204 and
No. 11621 N/1) by the Bundeswirtschaftsminister and by the Fonds
der Chemischen Industrie (PhD fellowship to K.S.). We thank the
Südzucker AG, Mannheim/Ochsenfurt and Dr. E. M. Belgsir, Uni-
versity of Poitiers, France for providing equipment and HPLC ana-
lyses and the Henkel AG, Düsseldorf for dodecyl
D-glucopyranoside.
MS (ESI-MS, nanospray, negative ions, solvent H2O): m/z (%) =
1204.4 [(M(31) – H)–, 7], 1189.3 [(M(30) – H)–, 29], 1175.4
Synthesis 1999, No. 5, 864–872 ISSN 0039-7881 © Thieme Stuttgart · New York

872
K. Schnatbaum, H. J. Schäfer
PAPER
(27) Heeres, A.; van Doren, H. A.; Bleeker, I. P.; Gotlieb, K. F.
WO Patent 9636621, 1996; Chem. Abstr. 1997, 126, 75187.
(28) Medgyes, A.; Farkas, E.; Lipták, A.; Pozsgay, V. Tetrahedron
1997, 53, 4159.
(29) Büschken, W.; Kaufhold, M.; Bickert, P. EP Patent 0574667,
1993; Chem. Abstr. 1995, 120, 270120.
(30) Bobbitt, J. M.; Flores, M. C. L. Heterocycles 1988, 27, 509.
(31) Yamaguchi, M.; Miyazawa, T.; Takata, T.; Endo, T. Pure
Appl. Chem. 1990, 62, 217.
(32) Yamauchi, Y.; Maeda, H.; Ohmori, H. Chem. Pharm. Bull.
1996, 44, 1021.
(33) Yamauchi, Y.; Maeda, H.; Ohmori, H. Chem. Pharm. Bull.
1997, 45, 2024.
(34) Kunz, M.; Recker, C. Carbohydr. Europe 1995, 13, 11.
(35) Böcker, T.; Thiem, J. Tenside Surf. Det. 1989, 26, 318.
(36) Röper, H. Starch/Stärke 1993, 45, 2.
(37) Heeres, A.; van Doren, H. A.; Gotlieb, K. F.; Bleeker, I. P.
Carbohydr. Res. 1997, 299, 221.
References
(1) Part 65: Weiper-Idelmann, A.; aus dem Kahmen, M.; Schäfer,
H. J.; Gockeln, M. Acta Chem. Scand. 1998, 52, 672.
(2) van Bekkum, H. In Carbohydrates as Organic Raw Materi-
als; Lichtenthaler, F. W., Ed.; VCH: Weinheim, 1991; p 289.
(3) Röper, H. In Carbohydrates as Organic Raw Materials;
Lichtenthaler, F. W., Ed.; VCH: Weinheim, 1991; p 267.
(4) Mallat, T.; Baiker, A. Catal. Today 1994, 19, 247.
(5) Gallezot, P.; Besson, M. Carbohydr. Europe 1995, 13, 5.
(6) Abbadi, A.; van Bekkum, H. In Carbohydrates as Organic
Raw Materials III; VCH: Weinheim, 1996; p 37.
(7) de Nooy, A. E. J.; Pagliaro, M.; van Bekkum, H.; Besemer, A.
C. Carbohydr. Res. 1997, 304, 117.
(8) Dimitrijevich, S. D.; Tatarko, M.; Gracy, R. W.; Linsky, C. B.;
Olsen, C. Carbohydr. Res. 1990, 195, 247.
(9) Heyns, K.; Paulsen, H. Adv. Carbohydr. Chem. Biochem.
1962, 17, 169.
(10) de Nooy, A. E. J.; Besemer, A. C.; van Bekkum, H. Synthesis
1996, 1153.
(11) Casciani, R. V.; Parfait, P. J. M.; McGraw, G. L. DE Patent
4209869, 1992; Chem. Abstr. 1993, 119, 9389.
(12) Ito, K.; Bobbitt, J. M.; Rusling, J. F. Proc. Electrochem Soc.
(Proceedings of the Fifth International Symposium on Redox
Mechanisms and Interfacial Properties of Molecules of Biolo-
gical Importance, 1993), 1993, 93-11, 260.
(13) Davis, N. J.; Flitsch, S. L. Tetrahedron Lett. 1993, 34, 1181.
(14) Davis, N. J.; Flitsch, S. L. J. Chem. Soc., Perkin Trans 1 1994,
359.
(15) de Nooy, A. E. J.; Besemer, A. C.; van Bekkum, H. Recl. Trav.
Chim. Pays-Bas 1994, 113, 165.
(16) Besemer, A. C.; de Nooy, A. E. J. WO Patent 9507303, 1995;
Chem. Abstr. 1995, 123, 202726.
(17) de Nooy, A. E. J.; Besemer, A. C.; van Bekkum, H. Tetrahe-
dron 1995, 51, 8023.
(18) de Nooy, A. E. J.; Besemer, A. C.; van Bekkum, H. Carbohy-
dr. Res. 1995, 269, 89.
(19) Verraest, D. L.; Peters, J. A.; van Bekkum, H. Zuckerind.
1995, 120, 799.
(38) Graefe, G. Die Stärke 1953, 5, 205.
(39) Goren, M. B.; Jiang, K.-S. Carbohydr. Res. 1980, 79, 225.
(40) Edye, L. A.; Meehan, G. V.; Richards, G. N. J. Carbohyd.
Chem. 1991, 10, 11.
(41) Edye, L. A.; Meehan, G. V.; Richards, G. N. J. Carbohydr.
Chem. 1994, 13, 273.
(42) Kunz, M.; Puke, H.; Recker, C.; Scheiwe, L.; Kowalczyk, J.
EP Patent 0651734, 1995; Chem. Abstr. 1995, 122, 56411.
(43) Kunz, M.; Schwarz, A.; Kowalczyk, J. EP 0775709, 1997.
(44) Fritsche-Lang, W.; Leupold, E. I.; Schlingmann, M. DE Pa-
tent 3535720, 1987; Chem. Abstr. 1987, 107, 59408.
(45) Lichtenthaler, F. W.; Mondel, S. Pure Appl. Chem. 1997, 69,
1853.
(46) Yoon, J.; Hong, S.; Martin, K. A.; Czarnik, A. W. J. Org.
Chem. 1995, 60, 2792.
(47) Casu, B.; Scovenna, G.; Cifonelli, A. J.; Perlin, A. S. Carbo-
hydr. Res. 1978, 63, 13.
(48) Lewis, A. J.; Bernstein, S. US Patent 4247535, 1981; Chem.
Abstr. 1981, 94, 214614.
(49) Weselake, R. J.; Hill, R. D. Carbohydr. Res. 1982, 104, 334.
(50) Gorin, P. A. J.; Mazurek, M. Can. J. Chem. 1975, 53, 1212.
(51) Matsuhiro, B.; Zanlungo, A. B.; Dutton, G. G. S. Carbohydr.
Res. 1981, 97, 11.
(20) Li, K.; Helm, R. F. Carbohydr. Res. 1995, 237, 249.
(21) Györgydeák, Z.; Thiem, J. Carbohydr. Res. 1995, 268, 85.
(22) de Nooy, A. E. J.; Besemer, A. C.; van Bekkum, H.; van Dijk,
J. A. P. P.; Smit, J. A. M. Macromolecules 1996, 29, 6541.
(23) Rundlöf, T.; Weintraub, A.; Widmalm, G. Carbohydr. Res.
1996, 291, 127.
(24) Rundlöf, T.; Widmalm, G. Anal. Biochem. 1996, 243, 228.
(25) Wong, M. F.; Weiss, K. L.; Curley, R. W., Jr. J. Carbohydr.
Chem. 1996, 15, 763.
(52) Analysis kindly performed by W. Kundel, Südzucker AG,
Mannheim/Ochsenfurt.
(53) Parpot, P.; Kokoh, K. B.; Belgsir, E. M.; Léger, J.-M.; Beden,
B.; Lamy, C. J. Appl. Electrochem. 1997, 27, 25.
Article Identifier:
1437-210X,E;1999,0,05,0864,0872,ftx,en;H09198SS.pdf
(26) Chang, P. S.; Robyt, J. F. J. Carbohydr. Chem. 1996, 15, 819.
Synthesis 1999, No. 5, 864–872 ISSN 0039-7881 © Thieme Stuttgart · New York