Selective TEMPO-catalyzed chemicals vs. electrochemical oxidation of carbohydrate derivatives

Article abstract of DOI:10.1080/07328300600636819

TEMPO-catalyzed electrochemical oxidation of carbohydrate derivatives was performed and compared with chemical oxidation, which requires the use of co-oxidants. Allyl-protected derivatives could be readily oxidized by both methods. Electrochemical selecti

Full text of DOI:10.1080/07328300600636819

Journal of Carbohydrate Chemistry, 25:253–266, 2006
Copyright # Taylor & Francis Group, LLC
ISSN: 0732-8303 print 1532-2327 online
DOI: 10.1080/07328300600636819
Selective TEMPO-Catalyzed
Chemicals vs.
Electrochemical Oxidation
of Carbohydrate Derivatives
Maximilien Barbier
´
´
Laboratoire des Glucides, CNRS UMR 6219, Faculte des Sciences, Universite de
Picardie “Jules Verne”, Amiens, France
Tony Breton and Karine Servat
´
Laboratoire de Catalyse en Chimie Organique, CNRS UMR 6503, Universite de
Poitiers, Poitiers Cedex, France
Eric Grand
´
´
Laboratoire des Glucides, CNRS UMR 6219, Faculte des Sciences, Universite de
Picardie “Jules Verne”, Amiens, France
Boniface Kokoh
´
Laboratoire de Catalyse en Chimie Organique, CNRS UMR 6503, Universite de
Poitiers, Poitiers Cedex, France
´
Jose Kovensky
´
´
Laboratoire des Glucides, CNRS UMR 6219, Faculte des Sciences, Universite de
Picardie “Jules Verne”, Amiens, France
TEMPO-catalyzed electrochemical oxidation of carbohydrate derivatives was performed
and compared with chemical oxidation, which requires the use of co-oxidants. Allyl-pro-
tected derivatives could be readily oxidized by both methods. Electrochemical selective
Received July 22, 2005; accepted February 10, 2006.
´
Address correspondence to Jose Kovensky, Laboratoire des Glucides, CNRS UMR 6219,
´
´
Faculte des Sciences, Universite de Picardie “Jules Verne”, 33 rue Saint-Leu, 80039,
Amiens, France. E-mail: jose.kovensky@u-picardie.fr
253

M. Barbier et al.
254
oxidation of primary positions has been adapted to unprotected mono- and oligosac-
charides.
Keywords TEMPO, Selective oxidation, Allyl-protected carbohydrates
INTRODUCTION
In the last decade, the use of organic nitroxyl radicals has been introduced in
carbohydrate chemistry for the selective oxidation of primary alcohols.
Successful oxidations of primary alcohol groups of monosaccharides, oligosac-
charides, and polysaccharides to the corresponding carboxyl functionalities
have been reported.[1–13] The stable nitroxyl radical—2,2,6,6-tetramethyl-1-
piperidinyl-oxy (TEMPO)—is oxidized through
a one-electron transfer
reaction to the corresponding nitrosonium salt, which is the active oxidant in
the primary alcohol oxidation.[14,15] Nitroxyl radicals can be used in catalytic
amounts; the presence of a regenerating oxidant system is required. Typical
procedures using homogeneous (aq NaClO-KBr or NaBr) or biphasic systems
(water-CH3CN-NaClO-NaClO2) have been adapted to organic and water
soluble substrates, respectively.
Electrochemical oxidation of the hydroxylamine formed to regenerate
TEMPO is an interesting alternative to chemical co-oxidants.[16,17] We report
here our results for the electrochemical TEMPO oxidation of primary positions
of different carbohydrate derivatives compared with chemical oxidation.
RESULTS AND DISCUSSION
The results of chemical and electrochemical oxidation of a series of carbo-
hydrate compounds are summarized in Table 1. A typical voltammogram,
demonstrating the action of oxoammonium ions on protected carbohydrates,
is presented in Figure 1. The shape of the voltammogram in the presence of
allyl 2,3-di-O-benzyl-4-O-p-methoxybenzyl-a-D-galactopyranoside shows that
the oxidation begins at ca. 0.25 V (Ag/AgNO3) (i.e., after the formation of
oxoammonium ions). The plateau observed on the j-E profile suggests that
the oxidation mechanism is a controlled diffusion process.

Table 1: Carbohydrate derivatives used as starting materials and their oxidation products.
Time for total conversion/yield
TEMPO
TEMPO
Starting material
Product
H5IO6/CrO3
chemical
electrochem.
15 min 97%
4 days
method A
91%
21 h method C 56%
7
1
—
4 days
method A
58%
24 h method C 57%
24 h method C 50%
8
9
2
3
Degradation
4 days
method A
95%
(continued)

Table 1: Continued.
Time for total conversion/yield
TEMPO
TEMPO
Starting material
Product
H5IO6/CrO3
chemical
electrochem.
—
14 days
method A#
65%
29 h method D 70%
10
4
—
—
4 days
23 h method Dꢀ 97%
method A§
90%
11
12
5
no reaction
method B
8 days
48 h method D 86%
6
method A
74%
Chemical oxidation. Method A: Acetonitrile - phosphate buffer pH 6.7 - NaClO2 - NaClO. Method B: NaClO - KBr.
Electrochemical oxidation. Method C: CH3CN - 5% of 0.2 M NaClO4. Method D: Carbonate buffer (0.5 M, pH 10).
# After 14 days, the reaction was stopped at 80% conversion. Oxidation of 4 by method B gave mucic acid in 2 days.
§
Oxidation of 5 by method B is slower, and complete disparition of starting material was not observed.
ꢀ5% CH3CN was added to prevent foaming of the tensioactive compound 5 during stirring.

Electrochemical Oxidation
257
Figure 1: Cyclic voltammetry of 9.6 mg (0.3 equiv.) of TEMPO recorded at 50 mV s21 in
CH3CN/H2O (95/5), 0.2 M NaClO4, under stirred conditions on a vitreous carbon anode with 8
equiv. of 2,6-lutidine (. . .. . .), and in presence of 0.20 mmole of allyl 2,3-di-O-benzyl-4-O-p-
methoxybenzyl-a-D-galactopyranoside (—).
Protected Carbohydrate Derivatives (No Free Secondary
Alcohols)
Compounds 1 and 3 are galactose derivatives possessing their primary
hydroxyls as the unique unprotected function. Conventional chemical
methods should work well enough to obtain the oxidized products in good
yields. H5IO6-CrO3oxidation[18] of 1,2 : 3,4-di-O-isopropylidene-a-D-galactopyr-
anose 1 allowed to obtain, as expected, the galacturonic acid 7[19] in 15 min. In
this case, TEMPO-catalyzed oxidation, either chemical or electrochemical, did
not improve the yield, the reaction times being longer.
On the other hand, when allyl 2,3-di-O-benzyl-4-O-p-methoxybenzyl-a-D-
galactopyranoside (3) was submitted to the same H5IO6-CrO3 reaction
conditions, the degradation of starting material was observed, probably
due to the undesired deprotection of the acid-sensitive p-methoxybenzyl
group at HO-4, leading to further oxidation. Compound 3 was smoothly
converted to the corresponding acid 9 by TEMPO (NaClO2-NaOCl in
acetonitrile-phosphate buffer) in 4 days in very good yield. Electrochemical
oxidation of 3, performed in aqueous acetonitrile in the presence of 2,6-
lutidine, was disappointing: Degradation of the starting material was
observed, and the desired product 9 could be isolated in 30% yield. This
result is probably due to the radical cleavage of the p-methoxybenzyl

M. Barbier et al.
258
group. Oxidation of benzyl groups by oxoammonium salts has been pre-
viously reported,[20] and the presence of the p-methoxy susbtituent would
make the group easier to oxidize. However, in the chemical oxidation this
cleavage was not detected. A possible explanation is that the biphasic
medium used for the NaClO2 system prevents the formation of radical
species or their attack to the sensitive protecting group.
Partially Protected Carbohydrate Derivatives (One Free
Secondary Hydroxyl)
The TEMPO-NaClO system is useful for the selective oxidation of primary
positions in the presence of unprotected secondary hydroxyls, while no other
chemical oxidation (i.e., chromium-based reactives) can be employed.
The dibenzyl derivative 2[21] could be readily oxidized to 8, although in 58%
yield and after several days. Electrochemical oxidation allowed to reach
similar yield, but in shorter reaction times (24 h).
Unprotected Carbohydrate Derivatives (Several Free
Hydroxyls)
The transformation of carbohydrates by electrochemical oxidation is
carried out under mild conditions, avoiding the formation of side products
and the use of co-oxidants. The main interest is to analyze the behavior of
unprotected sugar derivatives in comparison to the chemical oxidation in a
homogeneous system. For water-soluble starting materials, the electrochemi-
cal reaction was performed in aqueous carbonate buffer. Allyl a-D-galactopyr-
anoside 4[22] and n-decyl b-D-glucopyranoside 5 were submitted to chemical
oxidation with TEMPO to give galacturonic acid 10 (see below) and glucuro-
nic acid 11, respectively. Both conditions A and B were tested for compound
5, due to its amphiphilic character. When KBr conditions were used, the
reaction did not reach completion and was slower. On the other hand,
the method A resulted more appropriately to prevent foaming, end the
oxidized product 11 was obtained in 4 days. Electrochemical oxidation of
both 4 and 5 proceeded in 29 h and 23 h, respectively, leading to 10 and 11
in very good yields.
Compatibility with Allyl Protecting Groups
The interesting results observed on chemical TEMPO oxidation of allyl-
containing compounds such as 2, 3, and 4 merit some comment. It has been
claimed that TEMPO-mediated oxidation with sodium hypochlorite was
incompatible with allyl ether-protected carbohydrates,[23] and that the appli-
cation of nitroxyl radicals in the presence of an allyl group would be impossible

Electrochemical Oxidation
259
as the double bond of this group is sensitive to radicals.[24] Actually, when we
performed the oxidation of allyl galactoside 4 by the method B (aq NaOCl,
KBr), the product obtained was mucic acid, thus indicating that the
anomeric allyl-protecting group was lost and both primary positions oxidized
to the dicarboxylic acid. On the other hand, compounds 2 and 3 were readily
oxidized to 8 and 9, respectively, in the standard conditions normally used
for organic soluble starting materials (method A: NaClO2 - NaOCl in water
acetonitrile), without cleavage of the allyl group. When we applied these
conditions to 4, the oxidation proceeded slowly but smoothly to give
compound 10. Therefore, we can conclude that the allyl group is not incompa-
tible with TEMPO oxidation. To prevent allyl cleavage, it is necessary to
perform the oxidation without the use of NaBr (or KBr) in the reaction
mixture. This effect is probably due to the known effect of enhancement of
radical reactivity produced by these salts. A drawback of this NaBr-free
system is the longer reaction times observed for oxidations (several days). Elec-
trochemical TEMPO oxidation of different allyl-containing derivatives avoids
this problem and afforded the expected carboxylic acids in good to excellent
yields; these reactions proceed in the absence of NaBr or KBr salts.
Oxidation of Methyl b-D-Maltotrioside
Finally, we tried the oxidation of maltotrioside 6[25] to the corresponding
glucuronic acid trisaccharide 12. Unlike the monomers, a difference was
observed in the uptake of charge. In fact, after 48 h, the reaction seemed to
be stopped as no evolution in charge transfer was observed. For a calculated
Q of 223C, the effective charge transferred was 176C. This fact can simply be
due to a slow diffusion of oxidized species from the electrode, but it could
indicate that one of the primary alcohol functions is particularly resistant to
oxidation (i.e., the central C-6, or simply the last one to be oxidized). Analytical
high-pressure anion exchange chromatography (HPAEC-PAD) of the reaction
mixture before completion showed the presence of two products, but we were
not able to characterize the partial oxidized trisaccharide. The oxidized trisac-
charide was purified through Biogel P-2 and obtained as the trisodium salt.
Attempts to perform chemical oxidation of 6 by method B were unsuccessful,
and no change was observed even after a week. Surprisingly, oxidation could
be accomplished by method A, where a biphasic system is used, and the
reaction time was 8 days. Electrochemical oxidation is therefore a good alterna-
tive to obtain fully oxidized oligosaccharides.
CONCLUSIONS
The transformation of carbohydrates by electrochemical oxidation is carried
out under mild conditions, which avoid the production of side products,

M. Barbier et al.
260
except in the presence of p-methoxybenzyl-protecting groups. The complete
oxidation can be controlled by the quantity of electricity corresponding to
the regeneration of oxoammonium ions. This electrochemical process allows
shorter reaction times in comparison to a homogeneous system. We could
also determine that in the absence of bromide salts, the TEMPO oxidation
is compatible with allyl-protecting groups. On the other hand, electrochemi-
cal oxidation could be useful to perform extensive modifications of oligosac-
charides. Although tested on a 100 mg scale, the method described can be
easily adapted to multigram quantities for applying to synthesis of added
value products.
EXPERIMENTAL
Chemical Oxidation
Method A (organic-soluble compounds). To a solution of the carbohydrate
substrate and TEMPO (0.07 equiv.) in a 55 : 45 mixture of acetonitrile and
0.67 M phosphate buffer (pH 6.7), NaClO2 (20% aq solution, 2.0 equiv.) and
NaClO (15% aq solution, 0.06 equiv.) were added. After stirring for 4 days,
ether and Na2S2O3 (0.5 M aq solution) were added. The mixture was acidified
to pH 2 with conc aq HCl, and the aqueous phase was extracted with ether.
The organic layers were assembled, dried (anhydrous Na2SO4), filtered, and
evaporated to give the crude acid, which was purified by silica gel
chromatography.
Method B (water-soluble compounds). To a solution of the carbohydrate
substrate, TEMPO (0.1 equiv.) and NaBr (0.3 equiv.) in water (30 mL) were
added. NaClO (15% aq solution, 3.0 equiv.) were slowly added to the solution
previously brought to pH 10 by adding 4 M HCl. The pH was automatically
maintained at 10 by adding 0.5 M NaOH with a pH-stat. After stirring for
24 h, additional NaClO (15% aq solution, 3.0 equiv.) was added and the
mixture stirred another 24 h. After solvent evaporation or lyophilization, the
crude acid was purified and characterized.
Electrochemical Oxidation
Method C (organic-soluble compounds). To a solution of the starting carbo-
hydrate derivative (100 mg) and TEMPO (0.3 equiv.) in 95 : 5 acetonitrile -
0.2 M aqueous NaClO4 (40 mL), lutidine (8 equiv.) was added. The potential
was applied until a total charge of 4 Faraday per mole was consumed. After
solvent evaporation, ethyl acetate and 10% aq HCl were added. The organic
layer was separated, dried over anhydrous Na2SO4, filtered, and evaporated
to give the crude acid. Flash chromatography using the indicated eluant
gave pure products.

Electrochemical Oxidation
261
Method D (water-soluble compounds). A solution of the starting carbo-
hydrate derivative (100 mg) and TEMPO (0.3 equiv.) in 0.5 M aqueous
sodium carbonate buffer (40 mL, pH 10) was used. The potential was applied
until a total charge of 4 Faraday per mole was consumed. The mixture was
treated with Amberlite 200 (Hþ), filtered, and concentrated.
Working electrode: graphite
Counter electrode: Pt separated from the electrolyte with a proton exchange
membrane
Reference electrode: Ag/AgNO3 (0.1 M)
Allyl 2,3-di-O-benzyl-4-O-p-methoxybenzyl-a-D-galactopyranoside (3).
Allyl a-D-galactopyranoside 4[22] was first converted to its 4,6-O-p-methoxy-
benzylidene derivative (p-methoxybenzaldehyde dimethyl acetal, p-toluene-
sulfonic acid, DMF), followed by benzylation (NaH, BnBr, DMF) and finally
reductive opening of the p-methoxybenzylidene acetal (LiAlH4, AlCl3, dichloro-
methane-ether) to give 3 (59% overall yield), as syrup: [a]D þ 10 (c 0.23, CHCl3);
1H NMR (300 MHz, CDCl3) d 7.40–7.32 (m, 10H, HAr-Bn), 7.29 (d, 2H, Jo
0
0
8.3 Hz, PMB), 6.90 (d, 2H, Jo 8.3 Hz, PMB), 5.98 (dddd, 1H, J2 ,3 trans 17.2 Hz,
J2 ,3 cis 10.3 Hz, J1 a,2 5.5 Hz, J1 b,2 6.4 Hz, H-20), 5.35 (broad d, 1H, J2 ,3 trans
0
0
0
0
0
0
0
0
17.2 Hz, H-30a), 5.24 (broad d, 1H, J2 ,3 cis 10.3 Hz, H-30b), 4.97 (d, 1H, J1,2
3.2 Hz, H-1), 4.94 (d, 2H, Jgem 11.4 Hz, CHPh), 4.87 (d, 1H, Jgem 11.8 Hz,
CHPh), 4.80 (d, 1H, Jgem 11.4 Hz, CHPh), 4.73 (d, 1H, Jgem 11.8 Hz, CHPh),
0
0
0
0
4.63 (d, 1H, Jgem 11.4 Hz, CHPh), 4.19 (broad dd, 1H, Jgem 13.2 Hz, J1 a,2
5.5 Hz, H-10a), 4.11 (dd, 1H, J1,2 3.2 Hz, J2,3 9.9 Hz, H-2), 4.08–4.05 (m, 1H,
J1 b,2 6.4 Hz, H-10b), 4.02 (dd, 1H, J2,3 9.9 Hz, J3,4 2.8 Hz, H-3), 3.93 (broad d,
1H, J3,4 2.8 Hz, H-4), 3.85–3.78 (m, 4H, H-5, OMe), 3.73 (dd, 1H, Jgem
11.1 Hz, J5,6a 6.2 Hz, H-6a), 3.53 (m, 1H, Jgem 11.1 Hz, H-6b), 2.04 (s large,
1H, OH). 13C NMR (75,5 MHz, CDCl3) : 159.2 (Ci-OMe), 138.7, 138.4 (Ci-Ph),
133.8 (C-20), 130.1 (Ci-PMB), 130.0 (PMB), 128.2–127.3 (Ph), 117.8 (C-3’),
113.7 (PMB), 96.2 (C-1), 79.0 (C-3), 76.4 (C-2), 74.5 (C-4), 73.8, 73.4, 73.2
(CH2Ph), 70.3 (C-5), 68.2 (C-10), 62.2 (C-6), 55.1 (OMe).
0
0
ES-HRMS (þNa): Calcd. for C31H36O7Na: m/z 543.2359. Found: 543.2371.
1,2:3,4-di-O-isopropylidene-a-D-galactopyranosiduronic
acid
(7).
TEMPO-chemical oxidation: Method A (91% yield). TEMPO-electrochemical
oxidation: Method C (56% yield). E ¼ þ0.55 V (Ag/AgNO3). Q ¼ 215 C (theor.
154 C). Chromium-chemical oxidation: To a solution of 1,2:3,4-Di-O-isopropyli-
dene-a-D-galactopyranose (1, 105 mg, 0.403 mmol) in acetonitrile (2.0 mL) and
water (15 mL), a solution of H5IO6/CrO3 (2.45 mL, 4.84 mmol/1.2 mol % in
0.75% H2O/CH3CN) was added at 08C. After 15 min, Na2S2O3 (10 mL of a
14% aq solution) was added and the aqueous solution was washed with

M. Barbier et al.
262
dichloromethane (2 ꢁ 10 mL) and ethyl acetate (15 mL). The mixture was acid-
ified to pH 2 with conc aq HCl, and the aqueous phase was extracted with dichlor-
omethane (3 ꢁ 15 mL) and ethyl acetate (3 ꢁ 15mL). The organic layers were
assembled, dried (anhydrous Na2SO4), filtered, and evaporated to give the
crude acid, which was purified by silica gel chromatography (ethyl acetate,
then 1 : 1 ethyl acetate – methanol), leading to 7 (108mg, 97% yield) as a white
solid, which was recrystallized from diisopropylether-cyclohexane: m.p. 159.5–
1608C (lit.[19] 1578C); [a]D 2 49 (c 0.1, CH3OH) (lit.[19] 284, CHCl3). (Sell,
1
1938); H NMR (300 MHz, CD3OD) d 5.59 (d, 1H, J1,2 4.9 Hz, H-1), 4.72 (dd,
1H, J2,3 2.6 Hz, J3,4 7.7 Hz, H-3), 4.58 (dd, 1H, J3,4 7.7 Hz, J4,5 2.2 Hz, H-4),
4.44 (dd, 1H, J1,2 4.9 Hz, J2,3 2.6 Hz, H-2), 4.38 (d, 1H, J4,5 2.2 Hz, H-5), 1.50
(s, 3H, CH3), 1.40 (s, 3H, CH3), 1.34 (s, 3H, CH3), 1.33 (s, 3H, CH3). 13C NMR
(75,5 MHz, CD3OD) d 171.6 (C-6), 110.8 (CMe2), 110.2 (CMe2), 97.7 (C-1), 73.2
(C-4), 72.0 (C-3), 71.6 (C-2), 69.1 (C-5), 26.2 (2CH3), 25.0 (CH3), 24.7 (CH3).
ES-HRMS (þNa): Calcd. for C12H17O7Na2 (sodium salt): m/z 319.0770.
Found: 319.0776.
Allyl 2,3-di-O-benzyl-a-D-galactopyranosiduronic acid (8). TEMPO-
chemical oxidation: Method A (58% yield). TEMPO-electrochemical oxidation:
Method C (57% yield). E ¼ þ 0.55 V (Ag/AgNO3). Q ¼ 113 C (theor. 102 C).
Allyl 2,3-di-O-benzyl-a-D-galactopyranoside 2[21] was oxidized by and purified
by silica gel chromatography (9 : 1 to 1 : 1 ethyl acetate – methanol), leading
1
to 8 as a white solid, m.p. 215.5–216.58C; [a]D þ 64 (c 0.3, CHCl3); H NMR
0
0
(300 MHz, CD3OD) d 7.30–7.20 (m, 10H, Ph), 5.89 (ddt, 1H, J2 ,3 trans 17.4 Hz,
J2 ,3 cis 11.2 Hz, J1 ,2 5.3 Hz, H-20), 5.37 (broad s, 1H, H-1), 5.32 (broad d, 1H,
0
0
0
0
J2 ,3 trans 17.4 Hz, H-30a), 5.13 (d, 1H, J2 ,3 cis 11.2 Hz, H-30b), 4.76 (d, 1H, Jgem
10.5 Hz, CHPh), 4.71 (d, 1H, Jgem 11.4 Hz, CHPh), 4.67 (d, 1H, Jgem 11.4 Hz,
CHPh), 4.64 (d, 1H, Jgem 10.5 Hz, CHPh), 4.52 (broad s, 1 H, H-4), 4.35
0
0
0
0
(broad s, 1H, H-5), 4.20 (dd, 1H, Jgem 13.3 Hz, J1 a,2 4.7 Hz, H-10a), 4.09–4.06
(m, 2H, H-2, H-10b), 3.90 (dd, 1H, J2,3 10.0 Hz, J3,4 2.8 Hz, H-3). 13C NMR
(75,5 MHz, CD3OD) d 176.9 (C-6), 139.8, 139.7 (Ci-Ph), 135.3 (C-20), 129.3–
128.7 (Ph), 117.6 (C-30), 98.4 (C-1), 78.3 (C-3), 76.9 (C-2), 74.0 (CH2Ph), 73.9
(C-5), 73.0 (CH2Ph), 70.2 (C-10), 70.0 (C-4).
0
0
ES-HRMS (þNa): Calcd. for C23H26O7Na: m/z 437.1576. Found: 437.1580.
Allyl 2,3-di-O-benzyl-4-O-p-methoxybenzyl-a-D-galactopyranosiduro-
nic acid (9). TEMPO-chemical oxidation: Method A (95% yield). TEMPO-
electrochemical oxidation: Method C (50 % yield). E ¼ þ 0.55 V (Ag/AgNO3).
Q ¼ 237 C (theor. 79 C). Allyl 2,3-di-O-benzyl-4-O-p-methoxybenzyl-a-D-
-galactopyranoside (3) was oxidized by and purified by silica gel chromato-
graphy (9 : 1 ethyl acetate – methanol), leading to 9 as a white solid, m.p.
101.5–1028C; [a]D þ 83 (c 0.21, CHCl3); 1H NMR (300 MHz, CDCl3-D2O) d
0
0
7.40–7.20 (m, 12H, Ph), 6.75 (d, 2H, Jo 8.4 Hz, PMB), 5.79 (ddt, 1H, J2 ,3 trans

Electrochemical Oxidation
263
17.4 Hz, J2 ,3 cis 10.5 Hz, J1 ,2 6.0 Hz, H-20), 5.34 (broad s, 1H, H-1), 5.28 (d, 1H,
0
0
0
0
J2 ,3 trans 17.4 Hz, H-30a), 5.09 (d, 1H, J2 ,3 cis 10.5 Hz, H-30b), 4.80 (d, 2H, Jgem
10.5 Hz, CHPh), 4.72 (d, 2H, Jgem 11.8 Hz, CHPh), 4.67 (d, 2H, Jgem 12.1 Hz,
CHPh), 4.65–4.55 (m, 3H, CHPh), 4.49 (broad s, 1 H, H-4), 4.34 (broad s, 1H,
0
0
0
0
H-5), 4.11 (broad dd, 1H, Jgem 13.3 Hz, J1 ,2 4.5 Hz, H-10a), 4.05–4.00 (m, 1H,
H-10b), 4.00 (broad s, 2H, H-2, H-3), 3.67 (s, 3H, OMe). 13C NMR (75,5 MHz,
CDCl3) d 175.2 (C-6), 159.1 (Ci-OMe), 138.7, 138.4 (Ci-Ph), 133.9 (C-20), 130.2
(Ci- PMB), 129.8 (CAr-PMB), 128.2–127.3 (Ph), 117.2 (C-30), 113.5 (CAr-PMB),
96.8 (C-1), 78.0 (C-3), 76.9 (C-4), 76.1 (C-2), 74.8, 72.7 (CH2Ph), 72.3 (C-5),
68.8 (C-10), 54.9 (OMe).
0
0
ES-HRMS (þNa): Calcd. for C31H34O8Na: m/z 557.2151. Found: 557.2148.
Allyl a-D-galactopyranosiduronic acid (10). TEMPO-chemical oxidation:
Method A (65% yield). TEMPO-electrochemical oxidation: Method D (70%
yield). E ¼ þ0.30 V (MSE). Q ¼ 178 C (theor. 175 C). Allyl a-D-galactopyrano-
side 4[22] was oxidized and the crude acid was peracetylated (pyridine - acetic
acid) prior to purification by preparative HPLC (RP-C18 column, water-aceto-
nitrile gradient) to give allyl 2,3,4-tri-O-acetyl-a-D-galactopyranosiduro-
1
nic acid as a syrup; [a]D 225 (c 0.13, CH3OH); H NMR (300 MHz, CDCl3) d
0
0
0
0
0
0
0
0
5.90 (dddd, 1H, J2 ,3 trans 17.2 Hz, J2 ,3 cis 10.6 Hz, J1 a,2 5.0 Hz, J1 b,2 6.1 Hz,
H-20), 5.46 (d, 1H, J4,5 2.6 Hz, H-5), 5.32 (dd, 1H, J2 ,3 trans 17.2 Hz, Jgem
1.4 Hz, H-30a), 5.22 (dd, 1H, J2 ,3 cis 10.6 Hz, Jgem 1.4 Hz, H-30b), 5.15 (broad s,
0
0
0
0
2H, H-1-2), 5.06 (dd, 1H, J2,3 0.8 Hz, J3,4 5.6 Hz, H-3), 4.59 (dd, 1H, J3,4
5.6 Hz, J4,5 2.6 Hz, H-4), 4.20 (dd, 1H, J1 a,2 5.0 Hz, Jgem 13.1 Hz, H-10a), 4.03
0
0
(dd, 1H, J1 b,2 6.1 Hz, Jgem 13.1 Hz, H-10b), 2.24 (s, 3H, OMe), 2.13 (s, 3H,
OMe), 2.12 (s, 3H, OMe). 13C NMR (75,5 MHz, CDCl3) d 171.9 (CO2H),
170.5–169.8 (CO2CH3), 133.3 (C-20), 117.8 (C-30), 104.7 (C-1), 81.3 (C-2), 80.7
(C-4), 76.8 (C-3), 70.3 (C-5), 68.1 (C-10), 20.8–20.6 (CO2CH3).
0
0
ES-HRMS (þNa): Calcd. for C15H20O10Na: m/z 383.0954. Found: 383.0966.
n-Decyl b-D-glucopyranosiduronic acid (11). TEMPO-chemical oxidation:
Method A (90% yield). TEMPO-electrochemical oxidation: Method D (97%
yield). E ¼ þ0.40 V(MSE).Q ¼ 159C (theor. 122C). n-Decylb-D-glucopyranoside
5 was oxidized and the crude acid was purified by preparative HPLC (RP-C18
column, water-acetonitrile gradient) to give 11[26] as a white solid, m.p. 166.5–
1
1678C; [a]D 234 (c 0.11, CH3OH); H NMR (300MHz, CD3OD) d 4.23 (d, 1H,
J1,2 7.7 Hz, H-1), 3.98 (dt, 1H, Jgem 9.4 Hz, J1 a,2 6.8 Hz, H-10a), 3.61 (d, 1H, J4,5
0
0
8.9 Hz, H-5), 3.54 (dt, 1H, Jgem 9.4 Hz, J1 b,2 6.8 Hz, H-10b), 3.47 (t, 1H, J3,4
0
0
9.4 Hz, H-4), 3.41 (t, 1H, J3,4 9.4 Hz, H-3), 3.23 (t, 1H, J1,2 7.7 Hz, H-2), 1.64
(quint, 2H, J1,2 6.8 Hz, J2 ,3 6.8 Hz, H-20), 1.44–1.22 (m, 14 H, H30-90), 0.92
0
0
(t, 3H, J9 ,10 6.7 Hz, H-100). 13C NMR (75,5 MHz, CD3OD) d 176.9 (C-6), 104.4
(C-1), 77.9 (C-3), 74.9 (C-2), 73.7 (C-4), 71.0 (C-10), 33.1-23.7 (C-20-90), 14.4 (C-100).
ES-HRMS (þNa): Calcd. for C16H30O7Na: m/z 357.1889. Found: 357.1884.
0
0

M. Barbier et al.
264
Methyl a-D-glucopyranosiduronate-(1 ! 4)-a-D-glucopyranosiduro-
nate-(1 ! 4)-b-D-glucopyranosiduronate, trisodium salt (12). TEMPO-
chemical oxidation: Method B. After 4 days, no oxidized product was
detected. Method A (74% yield). TEMPO-electrochemical oxidation: Method
D (86% yield). E ¼ þ0.40 V (MSE). Q ¼ 176 C (theor. 223 C). Methyl b-D-mal-
totrioside 6[25] was oxidized and the crude mixture was purified through
Biogel P-2 (170 ꢁ 6 mm column, 50 mM NaHCO3). Fractions corresponding to
the product were collected and stirred 10 min with IR 120 plus (Hþ) resin.
After filtration, the solution was stirred 10 min with IR 120 plus (Naþ).
After filtration, the solvent was evaporated at 308C under diminished
pressure to give 12 as a white solid, m.p. 273.28C (dec.); [a]D þ 109 (c 0.12,
H2O); 1H NMR (300 MHz, D2O) d 5.44 (d, 1H, J1b,2b 3.8 Hz, H-1b), 5.41
(d, 1H, J1c,2c 3.8 Hz, H-1c), 4.26 (d, 1H, J1a,2a 8.0 Hz, H-1a), 3.94 (d, 1H, J4c,5c
10.0 Hz, H-5c), 3.85 (d, 1H, J4b,5b 10.2 Hz, H-5b), 3.83 (dd, 1H, J2c,3c 9.9 Hz,
J3c,4c 8.9 Hz, H-3c), 3.66 (m, 3H, H-3a, H-4a, H-5a), 3.60 (dd, 1H, J2b,3b
10.0 Hz, J3b,4b 9.1 Hz, H-3b), 3.57 (dd, 1H, J3c,4c 8.9 Hz, J4c,5c 10.0 Hz, H-4c),
3.44 (dd, 1H, J1c,2c 3.8 Hz, J2c,3c 9.9 Hz, H-2c), 3.41 (s, 3H, OMe), 3.38 (dd,
1H, J1b,2b 3.8 Hz, J2b,3b 10.0 Hz, H-2b), 3.27 (dd, 1H, J3b,4b 9.1 Hz, J4b,5b
10.2 Hz, H-4b), 3.19 (dd, 1H, J1a,2a 8.0 Hz, J2a,3a 9.3 Hz, H-2a). 13C NMR
(75,5 MHz, D2O) d 177.1, 176.1, 175.2 (C-6a, C-6b, C-6c), 103.4 (C-1a), 98.0
(C-1c), 97.5 (C-1b), 76.6, 76.5 (C-3a, C-4a, C-5a), 76.1 (C-4c), 73.3 (C-2a), 73.2
(C-3c), 72.7 (C-3b), 72.3 (C-4b, C-5b, C-5c), 71.9, 71.8 (C-2b, C-2c), 57.5
(OMe). a, b, c indicate the three sugar rings starting form right to left.
ES-HRMS (þNa): Calcd. for C19H25O19Na4: m/z 649.0581. Found:
649.0573.
ACKNOWLEDGMENTS
´
The authors acknowledge le Conseil Regional de Picardie (Programme Alterna-
´ ´
tives Vegetales).
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