Synthesis of Methyl 4-0-methyl-β -D-ribo-hex-3-ulopyranoside-1- 13C and Methyl 4-0-methyl-β -D-ribo-hex-3-ulopyranoside-3- 13C as fragment analogues of oxidized cellulose units

Article abstract of DOI:10.2174/157017810791112478

Model compounds of oxidized anhydroglucose units in cellulosic materials, carrying ¹³C isotopic labels at specific positions, have been synthesized starting from commercially available 1-¹³C-D-glucose (14.7%) and 3-¹³C-D- glucose (6.3%), respectively, over 10 linear steps. To ensure high yields, the synthetic route was optimized with non- labeled material beforehand. The labeled compounds are used in studies of chromophore formation, yellowing, brightness reversion and aging of cellulosics.

Full text of DOI:10.2174/157017810791112478

186
Letters in Organic Chemistry, 2010, 7, 186-190
Synthesis of Methyl 4-O-methyl-ꢀ-D-ribo-hex-3-ulopyranoside-1-13C and
Methyl 4-O-methyl-ꢀ-D-ribo-hex-3-ulopyranoside-3-13C as Fragment
Analogues of Oxidized Cellulose Units
Karin Krainza, Andreas Hofingera, Thomas Dietzb, Hans-Ulrich Süssb, Antje Potthasta and
Thomas Rosenau*,a
aDepartment of Chemistry and Christian-Doppler Laboratory, University of Natural Resources and Applied Life
Sciences Vienna (BOKU), Muthgasse 10, A-1190 Vienna, Austria; bEvonik-Degussa, Hanau, Germany
Received January 13, 2010: Revised January 28, 2010: Accepted January 28, 2010
Abstract: Model compounds of oxidized anhydroglucose units in cellulosic materials, carrying 13C isotopic labels at
specific positions, have been synthesized starting from commercially available 1-13C-D-glucose (14.7%) and 3-13C-D-
glucose (6.3%), respectively, over 10 linear steps. To ensure high yields, the synthetic route was optimized with non-
labeled material beforehand. The labeled compounds are used in studies of chromophore formation, yellowing, brightness
reversion and aging of cellulosics.
Keywords: Cellulose, aging, yellowing, brightness reversion, isotopic labeling, 3-keto-glucose.
INTRODUCTION
ꢀ-D-ribo-hex-3-ulopyranoside, labeled with >99% 13C at
either 1-C or 3-C is presented.
Cellulose is the most abundant, and – with regard to
technology and economic impact – also the most important
carbohydrate polymer and natural resource. Extraction of
celluloses from different sources and refinement of the
material towards paper and fiber production requires
numerous process steps (cooking and bleaching). Especially
bleaching that is based on oxidizing chemicals (O2, O3 or
H2O2 on one hand or ClO2 on the other hand) might cause
oxidation of the cellulose as reflected by introduction of
carbonyl and carboxyl groups [1]. Especially the carbonyl
groups are known to be the primary cause of brightness
reversion effects, i.e. re-yellowing of already bleached
materials, and precursor moieties for chromophore formation
[2, 3]. This topic is not only scientifically challenging, but
also of primary interest and economic importance in the pulp
and paper industry. Although such chromophores have been
isolated and characterized despite their extremely low
content in the ppb range [4,5], the chemical mechanisms of
the chromophore formation processes are still completely
unclear. To prove the hypotheses that oxidized
anhydroglucose units along the cellulose chains are the basic
chromophore precursors and that a fragmentation and
subsequent re-condensation of these units gives rise to the
observed colored, quinoid substances, the 13C-labeled model
compound methyl 4-O-methyl-ꢀ-D-ribo-hex-3-ulopyra-
noside was required that functions as oxidized cellulose
fragment analogue [6]. Introduction of the label was
especially interesting for the reactive positions 1 and 3. In
this study, a high-yield route towards methyl 4-O-methyl-
EXPERIMENTAL
General
All chemicals were available from commercial suppliers
and were of the highest purity available and used without
further purification. Reagent-grade solvents were used for all
extractions and workup procedures. Distilled water was used
for all aqueous extractions and for all aqueous solutions. The
use of brine refers to saturated aqueous NaCl. All reactions
involving non-aqueous conditions were conducted in flame-
dried glassware under an argon atmosphere. CH2Cl2 was
dried by refluxing over CaH, THF by refluxing over Na.
Molecular sieves were dried at 300°C. TLC was performed
using Merck silica gel 60 F254 pre-coated plates. Flash
chromatography was performed using Baker silica gel (40
ꢀm particle size). All given yields refer to isolated, pure
products. NMR spectra were generally recorded at 300.13
MHz for 1H and at 75.47 MHz for 13C NMR in CDCl3 as the
solvent, if not otherwise stated. The target products were
recorded at 400.13 MHz for H and at 100 MHz, for 13C
1
NMR. Chemical shifts, relative to TMS as internal standard,
are given in ꢁ values, coupling constants in Hz. 13C
resonances were assigned by means of COSY, APT, HSQC
and HMBC spectra. All syntheses were carried out in
parallel with labeled and non-labeled material. In the case of
the 3-13C-compound, NMR data were recorded only of the
final product, but not of the intermediates.
Synthesis of ꢀ-D-glucopyranose pentaacetate (2)
*Address correspondence to this author at the Department of Chemistry and
Christian-Doppler Laboratory, University of Natural Resources and Applied
Life Sciences Vienna (BOKU), Muthgasse 10, A-1190 Vienna, Austria; Tel:
+43-1-360066071; Fax: +43-1-360066071;
Acetic anhydride (10.58 mmol, 1.0 ml) was placed into a
round-bottom flask and cooled to 0°C. A drop of
concentrated perchloric acid was added followed by addition
of D-glucose (1, 0.82 mmol, 150 mg) in small portions.
E-mail: thomas.rosenau@boku.ac.at
1570-1786/10 $55.00+.00
© 2010 Bentham Science Publishers Ltd.

Synthesis of Methyl 4-O-methyl-ꢀ-D-ribo-hex-3-ulopyranoside-1-13C
Letters in Organic Chemistry, 2010, Vol. 7, No. 3
187
During the addition, the reaction temperature was monitored
not to exceed 40°C. The reaction mixture was stirred at r.t.
for 1 h and was used for the following step without
purification. Rf 0.31 (Hex/EtOAc, v/v = 1:1). Analytical data
corresponded to the literature [7].
compound 6 as white solid in quantitative yield, Rf 0.41
(EtOAc). The product was used in the following step without
further purification.
Synthesis of methyl 2,3-di-O-benzyl-4,6-O-benzylidene-ꢀ-
D-glucopyranoside (7)
Synthesis of ꢁ-bromo-2,3,4,6-tetra-O-acetyl-D-glucose (3)
Benzylidene acetal 6 (0.91 mmol, 256 mg) was dissolved
in dry THF (5.5 ml). NaH (4.55 mmol, 182 mg),
tetrabutylammonium iodide (10 mg) and benzyl bromide
(3.19 mmol, 0.38 ml) were added under cooling with ice
water. The reaction mixture was refluxed for 15 h in an
argon atmosphere. The reaction mixture was cooled to r.t.
and the excess of NaH was quenched with MeOH under
cooling with ice water. The mixture was diluted with EtOAc,
washed neutral with H2O, and washed with brine. The
organic layer was dried over Na2SO4 and the solvents
evaporated to dryness. The solid residue was purified by
column chromatography (Hex/EtOAc, v/v = 5:1) to afford 7
as a white solid in 73% yield (0.67 mmol, 311 mg).
Analytical data of the non-labeled compound agreed with
The reaction mixture containing 2 was cooled to 15°C
and phosphorus tribromide (2.13 mmol, 0.20 ml) was added
slowly, followed by careful addition of water (5.55 mmol,
0.10 ml). During both steps the temperature of the reaction
mixture was monitored to not exceed 25°C. The reaction
mixture was stirred at r.t. for 1.5 h, diluted with EtOAc,
neutralized with saturated aqueous NaHCO3. The organic
phase was washed with brine, dried over Na2SO4 and
concentrated under reduced pressure to yield the bromide as
a white solid. The crude bromide was co-evaporated three
times with dry toluene, dried under vacuum and directly used
for the following step. Rf 0.50 (Hex/EtOAc, v/v = 1:1).
Analytical data corresponded to the literature [7].
1
literature data [8]. 1-13C-labeled compound (7a): H NMR
Synthesis of methyl 2,3,4,6-tetra-O-acetyl-ꢀ-D-glucopyr-
anoside (4)
(CDCl3): ꢂ 3.40-3.48 (m, 2H, H-2, H-3), 3.58 (d, CH3, J C-1,H
= 4.8 Hz), 3.66-3.75 (m, 2H, H-4, H-5), 3.81 (m, 1H, H-6a),
4.37 (m, 1H, H-6b), 4.42 (dd, 1H, H-1, JC-1,H-1 = 160.9 Hz,
JH-1,H-2 = 7.9 Hz), 4.73-4.95 (m, 4H, 2 x CH2Ph), 5.55 (s, 1H,
CHPh), 7.27-7.91 (m, 15H, 3 x Ph). 13C NMR (CDCl3):
ꢂ105.23 (C-1).
Compound 3 was dissolved in dry CH2Cl2 (50 mmol, 3.2
ml). Powdered molecular sieves (4Å) and silver carbonate
(4.1 mmol, 1.13 g) were added and the suspension was
stirred under light protection and under argon at r.t. for 10
min. Dry MeOH (12 mmol, 0.5 ml) was added dropwise by
syringe through a septum. The reaction mixture was stirred
for 30 min for complete conversion of the starting material.
Solids were filtered off and washed with dry CH2Cl2, and the
combined filtrate was concentrated under reduced pressure.
The crude product was purified by column chromatography
(CH2Cl2 / MeOH, v/v = 20:1, Rf 0.58) providing the methyl
ꢀ-glucoside peracetate in 86% yield (0.70 mmol, 255 mg).
Synthesis of methyl 2,3,6-tri-O-benzyl-ꢀ-D-glucopyrano-
side (8)
In an argon atmosphere, triethylsilane (4.70 mmol, 0.75
ml) and trifluoracetic acid (4.70 mmol, 0.36 ml) were added
to a solution of compound 7 (0.67 mmol, 311 mg) in
anhydrous CH2Cl2 at –20°C. The reaction was warmed to
r.t., stirred for 3 h, diluted with EtOAc, neutralized with
saturated aqueous NaHCO3, and washed consecutively with
saturated aqueous Na2S2O3, saturated aqueous NaHCO3 and
brine. The organic layer was dried over Na2SO4 and
concentrated under reduced pressure. The residue was
purified by column chromatography (toluene/EtOAc, v/v =
9:2, Rf 0.36) to afford the desired product 8 as a white solid
in 66% yield (0.44 mmol, 206 mg). Non-labeled compound
Synthesis of methyl ꢀ-D-glucopyranoside (5)
For deprotection, compound 4 (1.06 mmol, 385 mg) was
dissolved in 4 ml of CH2Cl2 / MeOH (v/v = 1:4) and cooled
to 0°C. After addition of NaOMe (1M in MeOH, 0.42 mmol,
0.42 ml) the mixture was stirred 15 h under argon at r.t.,
neutralized with Dowex 50W-8X (H+) resin, filtered and
evaporated to dryness, providing 86% (0.91 mmol, 187 mg)
of the deprotected glucoside. Rf 0.7 (MeOH/CHCl3/H2O,
v/v/v = 10:10:1). Analytical data of the non-labeled
compound (5) agreed with those of the commercially
1
(8): H NMR (CDCl3): ꢁ 3.30-3.41 (m, 3H, H-2, H-3, H-4),
3.49 (s, 3H, 1-OCH3), 3.53 (m, 1H, H-5), 3.63 (m, 1H, H-
6a), 3.70 (m, 1H, H-6b), 4.25 (d, H-1, JH-1,H-2 = 7.5 Hz),
4.38-4.92 (m, 3x O-CH2Ph), 7.05-7.27 (m, 15H, Ph). 13C
NMR (CDCl3): ꢁ57.27 (1-OCH3), 70.45 (C-6), 71.75 (C-5),
73.84 (O-CH2-Ph), 74.84 (O-CH2-Ph), 75.41 (O-CH2-Ph),
81.81; 81.94; 84.16 (C-2, C-3, C-4), 104. 92 (C-1), 127.28–
138.78 (Ph). 1-13C-labeled compound (8a): 1H NMR
(CDCl3): ꢂ 3.35-3.48 (m, 3H, H-2, H-3, H-4), 3.56 (d, CH3,
JC-1,H = 4.5 Hz), 3.59-3.63 (m, 1H, H-5), 3.67-3.80 (m, 2H,
1
available substance. 1-13C-labeled compound (5a): H NMR
(D2O): ꢂ 3.25-3.34 (m, 1H, H-2), 3.38-3.56 (m, 3H, H-3, H-
4, H-5), 3. 61 (d, 3H, O-CH3, JC-1,H = 4.4 Hz), 3.76 (m, 1H,
H-6a), 3.97 (m, 1H, H-6b), 4.42 (dd, 1H, H-1, JC-1,H-1 = 160.4
Hz, JH-1,H-2 = 7.1 Hz). 13C NMR (D2O): ꢂ103.22 (13C-1).
Synthesis of methyl 4,6-O-benzylidene-ꢀ-D-glucopyrano-
side (6)
H-6a, H-6b), 4.32 (dd, 1H, H-1, JC-1,H-1 = 160.1 Hz, JH-1,H-2
=
8.0 Hz), 4.59; 4.71; 4.92 (3 x dd, 6H, 3 x CH2Ph), 7.26-7.38
(m, 15H, 3 x Ph). 13C NMR (CDCl3): ꢂ104.60 (C-1).
Methyl ꢀ-D-gluco-pyranoside (5) (0.91 mmol, 186 mg)
was dissolved in dry DMF (3 ml). Pre-dried p-
toluenesulfonic acid (0.05 mmol, 8.5 mg) and benzaldehyde
dimethylacetal (2.73 mmol, 0.41 ml) were added, and the
mixture was heated for 2 h at 50°C and 50 mbar. Solid
NaHCO3 was added to neutralize the reaction mixture. Solids
(mainly containing excess NaHCO3) were filtered off, and
the solution was co-evaporated with dry toluene to afford
Synthesis of methyl 2,3,6-tri-O-benzyl-4-O-methyl -ꢀ-D-
glucopyranoside (9)
Compound 8 (0.44 mmol, 206 mg) was dissolved in
anhydrous THF (7.2ml). NaH (1.82 mmol, 73 mg) was
added under cooling with ice water and the reaction mixture
was stirred in an Ar atmosphere for 30 min at r.t.. Methyl

188 Letters in Organic Chemistry, 2010, Vol. 7, No. 3
Krainz et al.
iodide (1.82 mmol, 0.11 ml) was added to the solution at
0°C, and stirring was continued for 3 h. Excess NaH was
quenched with MeOH while cooling with ice water, and the
mixture was diluted with EtOAc, neutralized with water and
washed with brine. The organic layer was dried over Na2SO4
and concentrated under reduced pressure. The residue was
purified by column chromatography (first: Hex, then:
Hex/EtOAc, v/v = 1:1 to elute the product) to yield
compound 9 in 94% yield (0.41 mmol, 198 mg). Non-labeled
2H, H-4, H-2), 3.41-3.48 (m, 1H, H-5), 3.54 (s, 3H, 4-
OCH3), 3.56 (d, CH3, 1-OCH3, J
= 4.6 Hz), 3.58-3.62
C-1,H
(m, 1H, H-3), 3.73 (dd, 1H, H-6a), 3.91 (dd, 1H, H-6b), 4.33
(dd, 1H, H-1, JC-1,H-1 = 161.0 Hz, JH-1,H-2 = 7.8 Hz). 13C NMR
(D2O): ꢀ103.15 (13C-1).
Synthesis of methyl 4-O-methyl-ꢁ-D-ribo-hex-3-ulopyr-
anoside (11)
Compound 10 (0.41 mmol, 86 mg) was dissolved in
CHCl3 (7 ml) and powdered molecular sieves (3Å) was
added followed by tributyltin(IV) oxide (0.82 mmol, 0.42
ml). The suspension was stirred and refluxed for 3 h under
argon, cooled to 0°C and bromine (approx. 1 mmol, 55 ꢀl)
was added until a faint coloration was observed. The
suspension was applied onto a silica gel column and washed
with CHCl3 (25 ml). The desired product was then eluted by
changing the solvent system to CH2Cl2/MeOH, v/v = 9:1.
Compound 11 was obtained in 79% yield (0.32 mmol, 67
mg) as a white solid. Rf 0.26 (CH2Cl2/MeOH, v/v = 9:1).
Non-labeled compound (11): 1H NMR (CDCl3):
ꢀ3.43ꢁ3.47 (m, 1H, H-5), 3.58 (s, 3H, 4-OCH3), 3.69 (s, 3H,
1-OCH3), 3.86 (dd, 1H, H-6a), 4.01 (dd, 1H, H-6b), 3.99-
4.12 (m, 2H, H-2, H-4), 4.26 (d, 1H, H-1, JH-1,H-2 = 7.9 Hz).
13C NMR (CDCl3): ꢀ57.76 (4-OCH3), 59.81 (1-OCH3), 61.79
(C-6), 75.35 (C-5), 77.34 (C-2), 80.40 (C-4), 105.75 (C-1),
205.12 (C-3). C8H14O6 (206.2): C 46.60, H 6.84, found: C
46.85, H 6.96. 1-13C-labeled compound (11a): 1H NMR
(CDCl3): ꢀ 3.42-3.47 (m, 1H, H-5), 3.58 (s, 3H, 4-OCH3),
3.63 (d, 1-OCH3, J C-1,H = 4.9 Hz), 3.86 (dd, 1H, H-6a), 4.01
(dd, 1H, H-6b), 4.04-4.13 (m, 2H, H-2, H-4), 4.26 (dd, 1H,
H-1, JC-1,H-1 = 164.4 Hz, JH-1,H-2 = 8.0 Hz). 13C NMR (CDCl3)
ꢀ 57.77 (4-OCH3), 59.81 (C-1-OCH3), 61.81 (d, J = 4.6 Hz,
1
compound (9): H NMR (CDCl3): ꢀ3.18ꢁ3.23 (m, 3H, H-4,
H-5, H-2), 3.38 (s 3H, 1-OCH3), 3.43 (d, 1H, H-3), 3.47 (s,
3H, 4-OCH3), 3.60 (m, 1H, H-6a), 3.66 (m, 1H, H-6b), 4.12
(d, 1H, H-1, JH-1,H-2 = 7.1 Hz), 4.46-4.82 (3 x dd, 6H, 3xO-
CH2-Ph), 7.15-7.27 (m, 15H, Ph). 13C NMR (CDCl3):
ꢀ57.07 (4-OCH3), 60.68 (1-OCH3), 69.08 (C-6), 73.53 (O-
CH2-Ph), 74.76 (O-CH2-Ph), 74.99 (C-5), 75.59 (O-CH2-
Ph), 79.83 (C-4), 82.18 (C-2), 84.61 (C-3), 104.71 (C-1),
1
127.63-138.72 (Ph). 1-13C-labeled compound (9a): H NMR
(CDCl3): ꢀ 3.25-3.41 (m, 3H, H-4, H-5, H-2), 3.48 (s, 3H,
OCH3), 3.52 (m, 1H, H-3), 3.56 (d, CH3, J
= 4.4 Hz),
C-1,H
3.67-3.78 (m, 2H, H-6a, H-6b), 4.28 (dd, 1H, H-1, JC-1,H-1
=
159.5 Hz, JH-1,H-2 = 7.7 Hz), 4.65; 4.73; 4.89 (3 x dd, 6H, 3 x
CH2Ph), 7.27-7.35 (m, 15H, 3 x Ph). 13C NMR (CDCl3):
ꢀ104.60 (C-1).
Synthesis of methyl 4-O-methyl-ꢁ-D-glucopyranoside (10)
Compound 9 (0.41 mmol, 198 mg) was dissolved in
MeOH (20 ml) and 40 mg of Pd/C (10%) were added and
stirred under hydrogen (10 bar) overnight at r.t. The catalyst
was filtered off and the solution evaporated to dryness to
obtain debenzylated compound 10 in quantitative yield
(0.41mmol, 86 mg). Rf 0.1 (CH2Cl2/MeOH, v/v = 9:1). Non-
labeled compound (10): 1H NMR (D2O): ꢀ3.16ꢁ3.28 (m, 2H,
H-4, H-2), 3.45 (m, 1H, H-5), 3.54 (s, 3H, 1-OCH3), 3.55 (s,
3H, 4-OCH3), 3.57-3.59 (m, 1H, H-3), 3.73 (dd, 1H, H-6a),
3.91 (dd, 1H, H-6b), 4.33 (d, 1H, H-1). 13C NMR (D2O):
ꢀ57.14 (4-OCH3), 59.98 (1-OCH3), 60.39 (C-6), 73.05 (C-3),
74.89 (C-2), 75.40 (C-5), 79.28 (C-4), 103.11 (C-1). 1-13C-
1
C-6), 75.37 (C-5), 77.47 (d, JC,C = 21.3 Hz, C-2), 80.43 (C-
4), 105.77 (1-13C), 205.13 (C-3). Microanalysis calcd. for
13CC7H14O6 (207.2): C 46.37, H 6.81, found: C 46.32, H
1
6.89. 3-13C-labeled compound (11b): H NMR (CDCl3): ꢀ
3.43-3.48 (m, 1H, H-5), 3.59 (s, 3H, 4-OCH3), 3.64 (s, 3H,
1-OCH3), 3.87 (m, 1H, H-6a), 4.02 (m, 1H, H-6b), 4.07-4.13
(m, 2H, H-2, H-4), 4.27 (d, 1H, H-1, JH-1,H-2 = 7.1 Hz). 13C
1
labeled compound (10a): H NMR (D2O): ꢀ 3.15-3.34 (m,
OAc
O
MeOH
Ag2CO3
PBr3
H2O
OAc
O
OH
O
Ac2O
HClO4
AcO
AcO
AcO
AcO
HO
HO
OAc
OMe
OH
AcO
OAc
OH
3
Br
2
1
OAc
O
PhCH(OMe)2 /
p-TsOH
O
OH
O
Ph
O
NaOMe
O
O
AcO
AcO
HO
HO
OMe
OMe
HO
OAc
OH
OH
6
5
4
OBn
NaH / BnBr /
NaH /
MeI
Ph
O
t-Bu4N+I-
Et3SiH /
TFA
O
BnO
O
OMe
HO
BnO
OMe
OBn
7
OBn
8
OBn
O
OH
O
OH
O
n-(Bu3Sn)2O
Br2 / H2O
H2
Pd/C
MeO
BnO
9
MeO
HO
MeO
OMe
OMe
OMe
OBn
OH
OH
11
10
O
Fig. (1). Synthesis scheme is shown for the non-labeled compound 11. The paths for the 1-13C compound 11a and the 3-13C compound 11b
were analogous, starting from correspondingly labeled D-glucose (1).

Synthesis of Methyl 4-O-methyl-ꢀ-D-ribo-hex-3-ulopyranoside-1-13C
Letters in Organic Chemistry, 2010, Vol. 7, No. 3
189
methyl glucoside. The final, optimized reaction sequence
implied ten steps (Fig. 1) and overall yields of 14.7% for the
1-13C-labeled compound 11a and 6.3% for the 3-13C-labeled
compound 11b. Key steps were the moisture-sensitive
glycosylation and the regioselective benzylidene acetal ring
opening.
NMR (CDCl3): ꢀ 57.71 (4-OCH3), 59.76 (1-OCH3), 61.88
(C-6), 75.36 (C-5), 77.52 (C-2, JC-2,C-3 = 35.4 Hz), 80.49 (C-
4, JC-4,
= 41.7 Hz), 105.77 (C-1), 205.10 (3-13C).
C-3
13CC7H14O6 (207.2): C 46.37, H 6.81, found: C 46.29, H
6.92.
In the initial steps, peracetylated D-glucose (2) was
converted into its ꢂ-bromide according to the Helferich
protocol [7] and into the ꢁ-methyl glucoside under Koenigs-
Knorr conditions [10]. Among commonly used promoters,
such as silver triflate, mercuric bromide, mercuric oxide or
mercuric cyanide [10-12], 5 equivalents of silver carbonate
and the solvent mixture dichloromethane / methanol (v/v =
5:1) worked best. Introduction of the 4,6-O-benzylidene
group followed by benzylation of the remaining hydroxyl
groups resulted in a rather apolar compound that was
conveniently purified by column chromatography.
Regioselective opening of the benzylidene acetal to obtain 8
bearing a free hydroxyl group at C-4 was achieved by use of
RESULTS AND DISCUSSION
The basic synthetic approaches to build up the desired
cellulosic model compounds have been published by our
group [6, 8, 9], but had to be extended (Fig. 1). Careful
optimization towards maximum yields was required due to
the high costs of the 13C-labeled materials. While work with
non-labeled compounds could be based on the use of
commercially available methyl ꢁ-D-glucopyranoside, the
syntheses of the labeled model compounds necessitated the
use of labeled D-glucoses as the only commercially available
starting materials – which meant four additional synthesis
steps including the high-yield glycosidation to form the ꢁ-
Fig. (2). 1H NMR spectra (CDCl3, 400 MHz) spectra of methyl 4-O-methyl-ꢁ-D-ribo-hex-3-ulopyranoside: non-labeled (11, lower
spectrum), 1-13C (11a, middle spectrum), and 3-13C (11b, upper spectrum).
Fig. (3). 13C NMR spectra (APT, CDCl3, 100 MHz) of methyl 4-O-methyl-ꢁ-D-ribo-hex-3-ulopyranoside: non-labeled (11, lower spectrum),
1-13C (11a, middle spectrum), and 3-13C (11b, upper spectrum).

190 Letters in Organic Chemistry, 2010, Vol. 7, No. 3
Krainz et al.
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First isolation and identification of residual chromophores from
aged bleached pulp samples. Holzforschung 2007, 61, 656-661.
Rosenau, T.; Potthast, A.; Milacher, W.; Hofinger, A.; Kosma, P.
Isolation and identification of residual chromophores in cellulosic
materials. Polymer 2004, 45, 6437-6443.
Röhrling, J.; Potthast, A.; Rosenau, T.; Adorjan, I.; Hofinger, A.;
Kosma, P. Synthesis of oxidized methyl 4-O-methyl-b-D-
glucopyranoside and methyl b-D-glucopyranosyl-(1ꢀ4)-b-D-
glucopyranoside derivatives as substrates for fluorescence labeling
reactions. Carbohydr. Res. 2002, 337, 691-700.
Helferich, B.; Joachim, Z. Synthese einiger disaccaride. Chem. Ber.
1962, 93, 2604-2611.
Adorjan, I.; Mereiter, K.; Pauli, J.; Jäger, C.; Rosenau, T.; Potthast,
A.; Kosma, P. Crystal and Molecular structure of methyl 4-O-
triethylsilane and THF [13]. The alternative ring opening
with sodium cyanoborohydride / HCl [14] was tested as well
but showed considerably more byproducts. The deprotected
4-OH was methylated with methyl iodide, subsequent
debenzylation was performed with Pd/C (10%) and H2 at 10
bar. Lower hydrogen pressure caused incomplete
debenzylation. The final oxidation step, regioselective at
position 3, used the bis-tributyltin oxide / bromine protocol
[15, 16], whereas Swern oxidation as used in our previous
work [6, 8] was much less successful.
[3]
[4]
[5]
[6]
NMR analysis of the labeled compounds corresponded to
the data achieved with non-labeled material, but the 13C-
enriched positions caused additional homo- (C – C) and
1
heteronuclear (C – H) couplings. The H and 13C spectra of
the non-labeled product 11 in comparison to the 1-13C
compound 11a and the 3-13C substance 11b are given in
Figs. (2 and 3), respectively.
[7]
[8]
methyl-ꢀ-d-ribo-hex-3-ulopyranoside. Carbohydr. Res. 2004, 339,
795-799.
CONCLUSIONS
[9]
Yoneda, Y.; Kawada, T.; Rosenau, T.; Kosma, P. Synthesis of
methyl 4'-O-methyl-13C12-ꢀ-D-cellobioside from 13C6-D-glucose.
Part 1: reaction optimization and synthesis. Carbohydr. Res. 2005,
340, 2428-2435.
A ten-step synthetic route to 13C-labeled methyl 4-O-
methyl-ꢀ-D-ribo-hex-3-ulopyranosides as model compounds
for oxidized anhydroglucose units in celluloses was
presented. The reaction products, analyzed with modern
NMR techniques, will be the basis of further studies into
chromophore formation processes in cellulosic materials.
[10]
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Mukherjee, D.; Yousuf, S.K.; Taneja, S.C. Indium trichloride
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[13]
[14]
[15]
ACKNOWLEDGEMENTS
The financial support of Evonik-Degussa Germany and
of the Austrian Forschungsförderungsgesellschaft (Bridge
project 812129) is gratefully acknowledged.
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