Experimental observations on the reductive cleavage of endo and exo 3,4-O-benzylidene fucopyranoside derivatives

Article abstract of DOI:10.1016/j.carres.2021.108338

Reductive cleavage of methyl 3,4-O-benzylidene-α-L-fucopyranosides with BH₃·THF-TfOH and NaCNBH₃-TfOH systems resulted in enhanced reaction rates and selectivity compared to BH₃·THF-Bu₂BOTf. With this latter sys

Full text of DOI:10.1016/j.carres.2021.108338

Carbohydrate Research 505 (2021) 108338
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Carbohydrate Research
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Experimental observations on the reductive cleavage of endo and exo
3,4-O-benzylidene fucopyranoside derivatives
1
*
´
´
Maciej Studzian , María-Elena Perez, María-Selma Arias-Perez
´
´
´
´
Departamento de Química Organica y Química Inorganica, Universidad de Alcala, 28805, Alcala de Henares, Madrid, Spain
A R T I C L E I N F O
A B S T R A C T
Keywords:
Reductive cleavage of methyl 3,4-O-benzylidene-α-L-fucopyranosides with BH3⋅THF-TfOH and NaCNBH3-TfOH
Fucopyranosides
3,4-O-benzylidene acetals
Reductive opening
Regioselectivy
systems resulted in enhanced reaction rates and selectivity compared to BH3⋅THF-Bu2BOTf. With this latter
system, the nature of the O-2 substituent exerted a clear control on the reactivity but practically did not affect the
regioselectivity. With TfOH the direction of cleavage was determined, as expected, by the configuration of the
acetal carbon atom, but slightly influenced by its competitive epimerization. Protic conditions provided higher
regioselectivity in the openings of the exo isomers, affording a useful approach to the practical synthesis of 3-O-
benzyl ethers.
¨
Bronsted acid activation
Bu2BOTf
1. Introduction
BH3⋅NMe3 [8,9a,d], BH3⋅SMe2 [8,10], alone or in presence of AlCl3 [8,
9a,d], BF3⋅OEt2 [9c], triflates [7,9b,c,e,10,11], CF3SO3H (TfOH) [9e];
Carbohydrate moieties often play an essential role in biological
processes and can regulate the function and biocompatibility of multi-
valent systems owing to their structural features and unique properties
[1–3]. Among the different design strategies, carbohydrate-based ap-
proaches have received widespread attention for the development of
multifunctional glycomimetics with biomedical applications [4]. Se-
lective strategies for the synthesis of saccharide building blocks [5] are
important tools to generate multiple structural topologies as potential
bioactive derivatives for the diagnosis, prevention and treatment of a
wide variety of pathologies [2–4].
DIBAL-H [11,12], or DIBAL-H/BF3⋅OEt2 [12c]; NaCNBH3–HCl [6d,8,
13d,e,f], or CF3COOH (TFA) [11], CH3SO3H (MsOH) [13a], TfOH [13b,
c], silyl choride [11]; Et3SiH-TFA [7], or TfOH [13c,14a,c,e,f], BF3⋅OEt2
[7,14d], TiCl4 [14d], triflates [10,14b,d]). The regioselectivities, reac-
tion rates and yields of the reductive cleavage are determined by
structural –steric and electronic-factors as well as the nature of hydride
donor, acidic promoter, solvent, and reaction conditions. Despite the
variety of published methods, this transformation is often limited by
unpredictable yields or regioselectivities, as well as the sensitivities of
acid-labile or easily reducible functional groups.
Reductive ring-opening of acyclic acetals is a key tool in the selective
manipulations of neighbouring 1,2- or 1,3-hydroxyl groups in poly-
hydroxylic compounds. In the synthetic field of carbohydrate chemistry
such reaction has been widely applied to O-benzylidene acetals ꢀ 1,3-
dioxane and 1,3-dioxolane systemsꢀ in general and to 4,6-O-benzyli-
dene-type acetal derivatives in particular [5]. In order to develop
chemo-, stereo- and regioselective ring-opening methods a large number
of reagent systems have been introduced, and the mechanistic aspects of
the processes have been extensively investigated [5–14]. In this way,
aluminium- [5–8], boron- [5,7–13] and silicon-based [5,7,10,13,14]
Usually, the direction of cleavage for 1,3-dioxolane-type benzylidene
acetals is thought to be mainly determined by the configuration of the
acetalic center. From the comparison between the dioxolane openings
with different reagent systems, the reductive cleavage of the exo and
endo-isomers to give axial and equatorial hydroxyl derivatives, respec-
tively, has been formulated as a general trend for the regiochemical
outcome of these reactions [6b,c,d,9d,13d]. However, deviations of this
rule have been reported due to solvent effects and the participation of
the substituents at adjacent positions of the acetal ring [6d,e,f,12b,14d].
To our knowledge, only few works have been reported so far on the
reductive cleavage of 3,4-O-benzylidene acetal derivatives and contra-
dictory results have been obtained for the exo-isomers. For instance,
¨
hydride reagents alone or in combination with Lewis or Bronsted acids
have been reported. For example, LiAlH4 [6–8]; BH3⋅THF [7–11],
´
´
´
* Corresponding author. Departamento de Química Organica y Química InorganicaFacultad de Farmacia Universidad de Alcala Campus Universitario, 28805,
´
Alcala de Henares, Madrid, Spain.
´
E-mail address: selma.arias@uah.es (M.-S. Arias-Perez).
1
Present address, Department of Molecular Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, 90–237 Lodz, Poland.
https://doi.org/10.1016/j.carres.2021.108338
Received 22 March 2021; Received in revised form 19 April 2021; Accepted 4 May 2021
Available online 12 May 2021
0008-6215/© 2021 Elsevier Ltd. All rights reserved.

M. Studzian et al.
Carbohydrate Research 505 (2021) 108338
1-thio-β-L-fucopyranoside acetals followed the general rules [6e,13d].
However, the equatorial 3-O-benzyl derivative was not detected in the
ring-opening of both endo and exo-isomers of methyl 2-O-benzyl and
found in the reductive ring openings of 3-O-benzoyl-4,6-O-benzylide-
ne-D-glucopyranosides with BH3⋅NMe3–AlCl3, in which cases extensive
debenzoylation and reduction of benzoate to benzyl ether were observed
[4a].
2-O-methyl α and β 3,4-O-benzylidene-L-fucopyranosides, with DIBAL-H
or DIBAL-H/BF3⋅OEt2 that gave exclusively the axial 4-O-benzyl ether
[12c,d].
The ring-opening reactions of exo isomers 4 and 6 took place in sig-
nificant lower yields and 2-O-acetyl derivative 4 was found to be the least
reactive towards BH3⋅THF-Bu2BOTf [6b,c,d,9d,13d]. At 0 ◦C, 2-O-methyl
derivative 6 reacted smoothly affording an approximately 1:1 mixture of
3-O and 4-O-benzyl ethers 9 and 10 in moderate yield (68%) even after 3
h. No secondary products were detected and 30% of starting acetal 6 was
recovery. An increase in the amount of Lewis acid enhanced the rate of
both the ring-opening and side reactions; using 2 equiv. of Bu2BOTf at
ꢀ 20 ◦C 1,5-anhydro-L-fucitols were obtained as by-products from which
the 1,5-anhydro-4-O-benzyl-2-O-methyl-L-fucitol (12) could be isolated.
According to previous observations, the unusual formation of these com-
pounds upon reductive opening conditions may be justified by ring
opening of the benzylidene acetal followed by reductive cleavage of the
more stable glycosidic acetal [6d,13f]. At low temperatures, the reaction
was unsuccessful when applied to 2-O-acetyl derivative 4; after 4 h, 3-O
and 4-O-benzyl ethers were obtained in low yield (13%) in a ratio around
1:1.5 being the starting material the main component of the reaction
mixture. An increase in the reaction temperature improved the rate of the
reaction affording the best result at 25 ◦C during 1 h (45% of 9 and 10),
while longer reaction times (Table 1, entry 6) resulted in substantial
amounts of 1,5-anhydro-L-fucitols (55%) and 2-O-ethyl side-products
(29%).
Herein, we report a comparative study of the reductive opening of
3,4-O-benzylidene-
α-L-fucopyranosides
using
BH3⋅THF-Bu2BOTf,
BH3⋅THF-TfOH and NaCNBH3-TfOH systems. The fucose units appear
very frequently as key structural elements of tumor and pathogenic
mycobacteria antigens [1]. 3,4-O-Benzylidene acetals, 3-O- and
4-O-benzyl fucopyranoside derivatives are interesting intermediates for
the synthesis of multivalent glycomimetics as potential mycobacterial
and anticancer vaccines or antitumor agents [2–4]. To our knowledge,
the hitherto undescribed use of TfOH as acid promoter at low temper-
atures provides a useful approach to the practical synthesis of
3-O-benzyl ethers from 3,4-O-benzylidene fucosyl acetals.
2. Results and discussion
The 2-O-acetyl and 2-O-methyl derivatives of methyl 3,4-O-benzy-
lidene-α-L-fucopyranoside (3–6) were prepared from methyl α-L-fuco-
pyranoside using standard procedures [6d,15-18] (Scheme 1).
The reductive ring-opening of 2-O-acetyl and 2-O-methyl derivatives
3–6 using BH3⋅THF were performed in combination with either Bu2BOTf
[9c,e] or TfOH [13b,c] as acid promoters using molar ratio substrate:
BH3 1:10 at different reaction conditions. Table 1 shows the results
obtained. Using both systems, the cleavage of the most reactive endo
isomers 3 and 5 led exclusively to the axial ether (4-O-benzyl derivatives
7 and 9, Scheme 1). The starting benzylidene acetal was exhausted by
Interestingly, the unchanged starting acetal was always recovered
and the regiochemical outcome of reduction was practically indepen-
dent of the reaction conditions. Moreover, the reactivity seems to be
controlled by the nature of the substituent at 2-position corresponding to
the low reactivity of the ester group, as was previously found for related
derivatives [9a,10], but it exerts a small effect on the ratio of the 3-O and
4-O-benzyl ethers formed. These observations suggest that acetal carbon
epimerization does not occur in the reaction medium with the
BH3⋅THF-Bu2BOTf system. Consequently, the mixture of 3-O and
4-O-benzyl ethers could not be attributed to the presence of both endo
and exo isomers. The slower reduction rate and the regioselectiviy of exo
acetals might be the result of the large steric demand of the bulky Lewis
acid, which dictates a more congested environment in the initial com-
plexes (A3 and A4, Scheme 2) and hinders the possible pathways leading
◦
treatment with BH3⋅THF-Bu2BOTf at 0 C during 1 h and 2-O-methyl
derivative 5 afforded the 4-O-benzyl ether 7, with excellent yield (90%).
However, the reductive opening of 2-O-acetyl derivative 3 was accom-
panied by reduction of the acetyl to an ethyl group decreasing the yield
of the 2-O-acetyl-4-O-benzyl derivative (7, 64%), being the methyl
4-O-benzyl-2-O-ethyl-α-L-fucopyranoside (11) the major by-product
isolated (21%). As the reaction time or temperature decreased, the
reduction of the acetyl group became less important, but the yield of
benzyl ether 7 did not improve due to the formation of other unidenti-
fied by-products (Table 1, entries 2 and 3). A related behaviour had been
Scheme 1. Synthesis and reductive ring-openings of 2-O-acetyl and 2-O-methyl derivatives of endo and exo methyl 3,4-O-benzylidene-α-L-fucopyranosides 3–6.
Reagents and conditions: i) C6H5CH(OCH3)2/TsOH/CH3CN (endo:exo, 53:47); ii) a) Ac2O/DMAP/C5H5N; b) Chromatographic separation; iii) NaOMe/MeOH
(Zemplen deacetylation); iv) NaH/CH3I/DMF; v) Reducing systems: BH3⋅THF-Bu2BOTf; BH3⋅THF-TfOH; NaCNBH3-TfOH.
2

M. Studzian et al.
Carbohydrate Research 505 (2021) 108338
Table 1
Reductive ring-opening reactions of 3,4-O-benzylidene acetals 3–6 with BH3.THF.a.
Entry
Substrate
3 endo
4 exo
Acid promoterb
T(◦C)/Time
Benzyl etherc,dyield (%)
Starting acetalc (%)
Benzyl ethers ratioc
4-O-Bn
3-O-Bn
1
Bu2BOTf(1eq)
0/1h
64 (60)
65 (61)
54
–
7, 100
100
100
62
8, -
–
2
0/30min
ꢀ 20/1h
0/4h
–
3
–
–
4
13
62
30
–
38
36
42
10, -
50
52
8, -
72
10, -
–
5
25/1h
45(39)
13
64
6
25/3h
58
7
5 endo
6 exo
0/1h
90 (85)
68 (61)
62 (55)
83 (68)
86 (70)
8
–
9, 100
50
8
0/1(3)h
ꢀ 20/30min
ꢀ 35/1h
30
–
9
(2 eq)
48
10
11
12
13
14
15
3 endo
4 exo
TfOH(10 eq)
–
–
7, 100
28
5 endo
(1eq)
92
–
9, 100
100
100
17
(10 eq)
89 (78)
46
0/1h
–
–
–
83
6 exo
ꢀ 35/1h
87 (73)
a
b
c
All reactions were carried out using 1 M solution in THF, and a molar ratio substrate: BH3 = 1:10, [substrate] = 0.09 M.
Solution of Bu2BOTf (1 M) in CH2Cl2 and neat TfOH were used except for entry 12 in which case a solution of TfOH (0.22 M) in CH2Cl2 was employed.
Determined by 1H NMR spectroscopy (±1%).
d
Yields of isolated products are given in parenthesis.
to both products in a similar way.
Table 2
Reductive cleavage with the BH3⋅THF-TfOH system required a large
excess of the acid and low temperatures (Table 1, entries 10–15). Thus,
with 1 equiv. of TfOH at ꢀ 35 ◦C, the endo 2-O-methyl-benzylidene acetal
5 reacted slowly and only traces of 4-O-benzyl ether were obtained after
1 h (8%), recovering the starting material unchanged. Using a large
Reductive ring-opening reactions of 3,4-O-benzylidene acetals 3–6 using
NaCNBH3-TfOH in THF.a.
Entry
Substrate
Reductionb,c
yield (%)
Benzyl ether ratiob
4-O-Bn
3-O-Bn
◦
excess of TfOH (molar ratio substrate: BH3: TfOH 1:10:10) at ꢀ 35 C
1
2
3
4
3 endo
4 exo
96(75)
93(77)
92(83)
90(78)
7, 95
22
8, 5
78
during 1 h the reductive cleavage of all benzylidene acetals took place
efficiently with yields ≥ 83%. In these conditions, the reduction of the
acetyl to an ethyl group was not observed and 1,5-anhydro-L- fucitols
were found in 11–17%; however, at 0 ◦C these derivatives were the
major products (54% from acetal 5, Table 1, entry 14). Additionally, the
ring opening of the exo benzylidene acetals 4 and 6 afforded the ex-
pected 3-O-benzyl ether as the main products (3-O and 4-O-benzyl ethers
ratio ≥ 2.5: 1).
5 endo
6 exo
9, 88
27
10, 12
73
a
Reaction conditions: molar ratio substrate: NaCNBH3: TfOH = 1:10:10;
[substrate] = 0.03 M; ꢀ 35 ◦C/45 min.
b
Determined by 1H NMR spectroscopy (±1%).
c
Yields of isolated products are given in parenthesis.
¨
activation of the NaCNBH3 by the Bronsted acid to give H2BCN with a
Moreover, the reductive opening of benzylidene acetals 3–6 was
carried out using NaCNBH3 in presence of TfOH. Electrophilic activation
by TfOH has been frequently applied in the reductive openings with
Et3SiH [13c,14a,c,e,f] and BH3⋅THF [9e]. However in the case of
NaCNBH3 only two reports have been published [13b,c]. The authors
indicate that TfOH improves the average yields and enhances repro-
ducibility compared to hydrogen chloride gas used in the most wide-
spread protocol [6b,8,13d,e,f].
reactivity similar to BH3 in THF [8]. Nevertheless, BH3⋅THF is an easy to
handle reagent, and any trace of water reacts readily with excess borane,
preventing the need for rigorously anhydrous conditions. 1,5-Anhy-
dro-L-fucitols and other by-products were not detectable in yields
higher than 5%. The ring openings of exo isomers 4 and 6 led to mixtures
of regioisomers with 3-O-benzyl ethers being also favoured (7:8 = 3.5:1;
9:10 = 2.7:1). However, a slightly lower regioselectivity was found for
endo isomers 3 and 5 (Table 1 entries 10 and 13 and Table 2 entries 1 and
3). At shorter reaction times, the reductive opening was not complete
and the starting acetal was recovered as a mixture of both endo and exo
isomers. These data suggest that epimerization of acetal carbon atom
In this case, a large excess of TfOH (molar ratio substrate: NaCNBH3:
TfOH 1:10:10) and low temperatures are again essential (ꢀ 35 ◦C,
Table 2). Both BH3⋅THF-TfOH and NaCNBH3-TfOH systems provided
similar results, in accordance with earlier observations that proposed an
Scheme 2. Plausible pathways for the reductive ring-openings of 2-O-acetyl and 2-O-methyl derivatives of methyl 3,4-O-benzylidene-α-L-fucopyranoside 3–6.
3

M. Studzian et al.
Carbohydrate Research 505 (2021) 108338
took place under these reaction conditions. Results from control ex-
periments supported this statement. Thus, by treatment with TfOH-THF
(molar ratio substrate: TfOH 1:1) at ꢀ 35 ◦C during 30 min, exo
2-O-acetyl and endo 2-O-methyl benzylidene acetals 4 and 5 provided
mixtures of both endo and exo isomers with a ratio of 19:81 and 47:53,
respectively.
recorded on a Varian Mercury 300 Plus or VNMRS-500 spectrometer in
CDCl3 at 298 K using standard pulse sequences. Chemical shifts are re-
ported relative to the residual CHCl3 (δH 7.24 ppm) or CDCl3 (δC 77.00
ppm); resonance patterns are given with the notations s (singlet),
d (doublet), t (triplet), q (quartet), and m (multiplet); in addition, the
notations ap and br are used to indicate an apparent multiplicity and a
broad signal. Lorentz-Gauss transformation was used to improve the
resolution of the 1H NMR spectra. Errors: 1H, δ ± 0.01 ppm, J ± 0.1 Hz;
13C, δ ± 0.1 ppm.
These findings are in agreement with previous works showing that
¨
Bronsted acids exhibit strong catalytic activity and small steric
requirement, resulting in enhanced reaction rates and the possible for-
mation of an oxocarbenium ion in the rate-controlling step [8,9c]. Due
to the small size of H+, protonation is faster than the rate of ace-
tal-Bu2BOTf complex formation, and the relative stabilities of the oxo-
carbenium ions might be the product-determining factor. The greater
stability of the B2 and B3 species (Scheme 2) is consistent with the
observed regiochemical outcome. Therefore, the direction of cleavage is
determined, as expected, by the configuration of the acetal carbon atom,
but influenced by the competitive epimerization of this stereogenic
centre. In any case, reduction is faster than isomerization that is prac-
tically no discernible for endo acetals 3 and 5 with BH3⋅THF-TfOH giving
the 4-O-benzyl ethers exclusively (Table 1 entries 10 and 13) and exerts
a small contribution with NaCNBH3-TfOH resulting in a slight loss of
regioselectiviy (Table 2 entries 1 and 3). However, this competitive
process has a significant role in the reactions of exo isomers 4 and 6, with
a negative effect on the formation of the 3-O-benzyl ethers (Table 1,
entries 11 and 15 and Table 2 entries 2 and 4). These remarks also
appear to correlate with the slower reduction rate of exo acetals.
4.2. Synthesis of compounds 1–6
4.2.1. Methyl endo/exo 2-O-acetyl-3,4-O-benzylidene-α-L-fucopyranosides
(3 and 4)
A mixture of methyl α-L- fucopyranoside [15] (3.0 g, 16.8 mmol),
benzaldehyde dimethylacetal (4.26 g, 28 mmol) and a catalytic amount
of p-TsOH in dry acetonitrile (30 mL) was stirred at r. t. during 24 h [16].
The reaction was neutralized with triethylamine (1 mL) and after stir-
ring 30 min was treated with water. The organic layer was separated and
the aqueous phase was extracted with EtOAc. The combined organic
fractions were washed with saturated solution of NaHCO3 and brine,
dried and concentrated. Purification by flash chromatography (hexane:
EtOAc 1:1) led to a 53:47 mixture of endo (1) and exo (2) methyl 3,
4-O-benzylidene-α-L-fucopyranosides (3,49 g, 78%). To a stirred solu-
tion of the mixture of 1 and 2 (3.46 g, 13 mmol) in dry pyridine (40 mL)
◦
at 0 C was added Ac2O (2.5 mL, 25.2 mmol) and 4-(dimethyamino)
pyridine (150 mg) [17]. The stirring was maintained at r. t. for 20 h. The
reaction was quenched with cold water and diluted with CH2Cl2. The
organic layer was separated and the aqueous phase was extracted with
CH2Cl2. The combined organic fractions were washed with saturated
solutions of NH4Cl, NaHCO3, water and brine, dried and concentrated.
The mixture of acetylated isomers was separated by flash chromatog-
raphy (hexane: EtOAc 8:2) to yield pure endo (3, 1.8 g, 45%) and exo (4,
1.7 g, 42%) isomers.
3. Conclusion
In summary, BH3⋅THF-TfOH and NaCNBH3-TfOH systems provided
best results than BH3⋅THF-Bu2BOTf, that only furnished good yield and
selectivity in the case of endo methyl 2-O-methyl-3,4-O-benzylidene-
α
-L-
¨
fucopyranoside. Activation by the Bronsted acid resulted in enhanced
reaction rates and led to higher regioselectivity in the openings of exo
isomers. In these conditions, the direction of cleavage is determined, as
expected, by the configuration of the acetal carbon atom, but slightly
influenced by its competitive epimerization. By this way, 3-O-benzyl and
4-O-benzyl ethers can be obtained in synthetically useful yields from
3,4-O-benzylidene fucosyl acetals.
Methyl endo 2-O-acetyl-3,4-O-benzylidene-
α
-L-fucopyranoside
(3): white waxy solid; [
α
]
21 ꢀ 136 (c 1.2, CHCl3); Rf 0.43 (hexane/EtOAc
D
–
–
6:4); IR (film)
ν
3072, 3051, 2933, 1739 (C O), 1495, 1451, 1235,
1098, 1062 cmꢀ 1; 1H NMR (CDCl3, 300 MHz) δ 1.41 (d, 3H, J5,6 6.7 Hz,
CH3-6), 2.10 (s, 3H, CH3CO), 3.38 (s, 3H, 1-OCH3), 4.15 (dd, 1H, J3,4
5.8, J4,5 2.6 Hz, H-4), 4.17 (qd, 1H, J4,5 2.6, J5,6 6.7 Hz, H-5), 4.44 (dd,
1H, J2,3 7.9, J3,4 5.8 Hz, H-3), 4.84 (d, 1H, J1,2 3.6 Hz, H-1), 4.94 (dd, 1H,
4. Experimental section
J
1,2 3.6, J2,3 7.9 Hz, H-2), 5.87 (s, 1H, CHC6H5), 7.37 (m, 3H, m-H, p-H,
4.1. General methods
C6H5), 7.49 (m, 2H, o-H, C6H5); 13C NMR (CDCl3, 75 MHz) δ 16.1 (CH3-
6), 21.0 (CH3CO), 55.5 (1-OCH3), 62.8 (C-5), 72.8 (C-2), 73.1 (C-3), 78.6
(C-4), 97.1 (C-1), 104.4 (CHC6H5), 126.9, 128.4, 129.5, 136.9 (C6H5),
170.4 (CO); MS (ESI +): m/z 309 [M+H]+; Anal. Calcd for C16H20O6: C,
62.33; H, 6.54. Found: C, 62.22; H, 6.61%.
All reagents were commercially available (Sigma-Aldrich) in high
purity and used as received. Solvents were dried using standard
methods. TfOH was dried over activated 3 Å molecular sieves and stored
under argon. Anhydrous MgSO4 was used to dry the organic layers
during workups and the removal of the solvents was done under vac-
uum. The reactions mixtures were monitored by thin-layer chromatog-
raphy (TLC) and their composition was determined by 1H NMR
spectroscopy. TLC was performed on precoated Kieselgel 60 F254
aluminium sheets; plates were eluted with hexane-EtOAc mixtures;
detection was first by UV and then by charring with sulphuric acid in
ethanol (1:4, v/v). Flash chromatography was performed on Merck
Silica Gel 60 (230–400 mesh) using hexane-EtOAc mixtures as eluent.
Optical rotations were measured in chloroform on a Perkin-Elmer 341
polarimeter. ESI mass (+mode) spectra were performed on a Thermo
Scientific TSQ Quantum LC/MS instrument. IR spectra were recorded on
a FT-IR Perkin-Elmer Spectrum 2000 spectrophotometer and the sam-
ples were prepared as KBr disk or by evaporation of a solution of the
compound in CHCl3 onto NaCl plate under a stream of argon. The
structure of all compounds was confirmed by 1H and 13C NMR spec-
troscopy. 2D NMR techniques were used for the identification and un-
ambiguous assignment of the proton and carbon resonances. All NMR
spectra (1H, 13C, 2D 1H–1H gCOSY, gC2HSQCSE, gCH2MBC) were
Methyl exo 2-O-acetyl-3,4-O-benzylidene-
α
-L-fucopyranoside
21
(4): viscous and colorless liquid; [
α]
ꢀ 170 (c 1.0, CHCl3); Rf 0.54
D
(hexane/EtOAc 6:4); IR (film)
ν 3070, 3050, 2938, 1736 (CO), 1494,
1452, 1236, 1091, 1050 cmꢀ 1; 1H NMR (CDCl3, 300 MHz) δ 1.38 (d, 3H,
J
5,6 6.5 Hz, CH3-6), 2.14 (s, 3H, CH3CO), 3.39 (s, 3H, 1-OCH3), 4.08 (m,
2H, H-4, H-5), 4.58 (dd, 1H, J2,3 8.4, J3,4 5.1 Hz, H-3), 4.87 (d, 1H, J1,2
3.6 Hz, H-1), 5.05 (dd, 1H, J1,2 3.6, J2,3 8.4 Hz, H-2), 6.15 (s, 1H,
CHC6H5), 7.34 (m, 3H, m-H, p-H, C6H5), 7.42 (m, 2H, o-H, C6H5); 13
C
NMR (CDCl3, 75 MHz) δ 16.4 (CH3-6), 21.0 (CH3CO), 55.5 (1-OCH3),
63.0 (C-5), 69.2 (C-2), 74.8 (C-3), 76.2 (C-4), 97.1 (C-1), 102.7
(CHC6H5), 126.2, 128.4, 129.5, 138.9 (C6H5), 170.6 (CO); MS (ESI +):
m/z 309 [M+H]+; Anal. Calcd for C16H20O6: C, 62.33; H, 6.54. Found: C,
62.45; H, 6.43%.
4.2.2. Methyl endo/exo 3,4-O-benzylidene-2-O-methyl-α-L-
fucopyranosides (5 and 6)
Zemplen deacetylation of compounds 3 or 4 (1.0 g, 3.24 mmol) was
carried out by treatment with a catalytic amount of NaOMe (21 mg) in
dry MeOH (40 mL) at r.t. for 5h with stirring [6d,18]. The mixture was
4

M. Studzian et al.
Carbohydrate Research 505 (2021) 108338
neutralized with Amberlite IR-120H+ resin and concentrated affording
after flash chromatography (hexane: EtOAc 1:1) derivatives endo (1,
664 mg, 77%), mp 102–104 ◦C, lit.16 104–105 ◦C, and exo (2, 750 mg,
87%), mp 89–92 ◦C, lit.16 92–93 ◦C. 1H and 13C NMR spectral data of
these compounds agree with those reported [16].
concentrated. The crude product was purified by flash chromatography.
Method B. After addition of a 1 M solution of BH3⋅THF complex in
THF (2 mL) to the benzylidene acetal (0.2 mmol) the solution was cooled
to ꢀ 35 ◦C and stirred for 10 min. The mixture was treated with TfOH
(0.18 mL, 2 mmol) ([substrate] = 0.09 M) and stirring was maintained
for 1h. The reaction was then quenched, worked up and the residue
purified as described in method A.
A stirred solution of the benzylidene acetals 1 or 2 (638 mg, 2.4
mmol) in dry DMF (5 mL) was treated with NaH (108 mg, 80%, 3.6
mmol) at 0 ◦C. After addition of methyl iodide (0.45 mL, 7.2 mmol) the
reaction temperature was allowed to reach r.t. and stirring was
continued for 2h [6d]. Then, MeOH was added to decompose the excess
of NaH and the mixture was concentrated. The residue was diluted with
Et2O, washed with water, saturated solution of NaHCO3 and brine, dried
and concentrated. Purification of crude products by flash chromatog-
raphy (hexane: EtOAc 6:4) led to methyl derivatives endo (5, 558 mg,
83%) and exo (6, 605 mg, 90%).
Method C. A mixture of the benzylidene acetal (0.2 mmol) and acti-
vated 3 Å molecular sieves (500 mg) in dry THF (4.4 mL) was stirred at r.
◦
t. for 1 h. The mixture was cooled to ꢀ 35 C and treated with a 1 M
solution of NaBCNH3 in THF (2 mL). After 5 min TfOH (0.18 mL, 2
mmol) was added ([substrate] = 0.03 M) and stirring was continued for
45 min. The reaction was quenched, worked up and the residue purified
as described above.
Epimerization experiments with TfOH. A solution of the benzylidene
acetal 4 or 5 (0.1 mmol) in dry THF (3.2 mL) containing activated 3 Å
molecular sieves (300 mg) was stirred at r.t. for 1 h. After cooling to
ꢀ 35 ◦C TfOH (0.1 mL, 0.11 mmol) was added ([substrate] = 0.03 M) and
the mixture was stirred for 30 min before being quenched and worked
up as described previously.
Methyl endo 3,4-O-benzylidene-2-O-methyl-
α
-L-fucopyranoside
21
◦
(5): white solid; mp 126–128 C; [
α
]
ꢀ 110 (c 1.0, CHCl3); Rf 0.60
(hexane/EtOAc 4:6); IR (film)
ν
3042D, 2941, 1496, 1454, 1270, 1080,
1051 cmꢀ 1; 1H NMR (CDCl3, 300 MHz) δ 1.42 (d, 3H, J5,6 6.6 Hz, CH3-
6), 3.35 (dd, 1H, J1,2 3.7, J2,3 7.7 Hz, H-2), 3.41 (s, 3H, 1-OCH3), 3.44 (s,
3H, 2-OCH3), 4.12 (dd, 1H, J3,4 5.9, J4,5 2.8 Hz, H-4), 4.15 (qd, 1H, J4,5
2.8, J5,6 6.6 Hz, H-5), 4.37 (dd, 1H, J2,3 7.7, J3,4 5.9 Hz, H-3), 4.77 (d,1H,
J1,2 3.7 Hz, H-1), 5.90 (s, 1H, CHC6H5), 7.37 (m, 3H, m-H, p-H, C6H5),
7.52 (m, 2H, o-H, C6H5); 13C NMR (CDCl3, 75 MHz) δ 16.2 (CH3-6), 55.5
(1-OCH3), 58.7 (2-OCH3), 62.8 (C-5), 75.6 (C-3), 78.6 (C-4), 79.6 (C-2),
98.0 (C-1), 103.7 (CHC6H5), 126.6, 128.3, 129.1, 138.0 (C6H5); MS (ESI
+): m/z 281 [M+H]+; Anal. Calcd for C15H20O5: C, 64.27; H, 7.19.
Found: C, 64.15; H, 7.31%.
Methyl 2-O-acetyl-4-O-benzyl-
α
-L-fucopyranoside (7): viscous
and colorless liquid; [
3:7); IR (film)
α]
D
21 ꢀ 131 (c 1.1, CHCl3); Rf 0.50 (hexane/EtOAc
ν
3440, br (OH), 2930, 2828, 1748 (CO), 1492, 1458,
1370, 1235, 1099, 1050 cmꢀ 1; 1H NMR (CDCl3, 300 MHz) δ 1.25 (d, 3H,
J5,6 6.6 Hz, CH3-6), 2.11 (s, 3H, CH3CO), 2.12 (s br, 1H, 3-OH), 3.35 (s,
3H, 1-OCH3), 3.66 (dd, 1H, J3,4 3.5, J4,5 1.3 Hz, H-4), 3.93 (qd, 1H, J4,5
1.3, J5,6 6.6 Hz, H-5), 4.00 (m, 1H, H-3), 4.70, 4.78 (AB system, 2H, J
ꢀ 11.6 Hz, CH2C6H5), 4.83 (d, 1H, J1,2 3.8, Hz, H-1), 5.03 (m, 1H, H-2),
7.32 (m, 5H, C6H5); 13C NMR (CDCl3, 75 MHz) δ 16.6 (CH3-6), 21.1
(CH3CO), 55.2 (1-OCH3), 66.0 (C-5), 68.9 (C-2), 71.9 (C-3), 76.0
(CH2C6H5), 80.6 (C-4), 97.4 (C-1), 128.0, 128.5, 137.9 (C6H5), 171.3
(CO)); MS (ESI +): m/z 311 [M+H]+; Anal. Calcd for C16H22O6: C,
61.92; H, 7.15. Found: C, 62.03; H, 7.03%.
Methyl exo 3,4-O-benzylidene-2-O-methyl-
α-L-fucopyranoside
21
◦
(6): white solid; mp 114–115 C; [
α
]
ꢀ 151 (c 1.0, CHCl3); Rf 0.54
(hexane/EtOAc 4:6); IR (film)
ν
3040D, 2967, 1498, 1457, 1272, 1089,
1039 cmꢀ 1; 1H NMR (CDCl3, 300 MHz) δ 1.37 (d, 3H, J5,6 6.8 Hz, CH3-
6), 3.42 (s, 3H, 1-OCH3), 3.50 (dd, 1H, J1,2 3.7, J2,3 7.9 Hz, H-2), 3.58
(3H, s, 2-OCH3), 4.01 (dd, 1H, J3,4 5.3, J4,5 2.4 Hz, H-4), 4.06 (qd, 1H,
Methyl 2-O-acetyl-3-O-benzyl-
α
-L-fucopyranoside (8): viscous
21
J
4,5 2.4, J5,6 6.8 Hz, H-5), 4.52 (dd, 1H, J2,3 7.9, J3,4 5.3 Hz, H-3), 4.86
and colorless liquid;
α
]
-127 (c 1.0, CHCl3); Rf 0.61 (hexane/EtOAc
(d, 1H, J1,2 3.7 Hz, H-1), 6.18 (s, 1H, CHC6H5), 7.35 (m, 3H, m-H, p-H,
C6H5), 7.45 (m, 2H, o-H, C6H5); 13C NMR (CDCl3, 75 MHz) δ 16.4 (CH3-
6), 55.6 (1-OCH3), 58.7 (2-OCH3), 62.9 (C-5), 76.0 (C-4), 76.7 (C-2),
77.1 (C-3), 97.8 (C-1), 102.6 (CHC6H5), 126.1, 128.4, 128.9, 139.4
(C6H5); MS (ESI +): m/z 281 [M+H]+; Anal. Calcd for C15H20O5: C,
64.27; H, 7.19. Found: C, 64.33; H, 7.08%.
3:7); IR (film)
ν
3442, Dbr (OH), 2920, 2818, 1745 (CO), 1496, 1452,
1371, 1230, 1094, 1053 cmꢀ 1; 1H NMR (CDCl3, 300 MHz) δ 1.29 (d, 3H,
J5,6 6.6 Hz, CH3-6), 2.08 (s, 3H, CH3CO), 2.41 (s br, 1H, 4-OH), 3.35 (s,
3H, 1-OCH3), 3.85 (m, 2H, H-3, H-4), 3.88 (qd, 1H, J4,5 1.3, J5,6 6.6 Hz,
H-5), 4.63, 4.66 (AB system, 2H, J ꢀ 12.0 Hz, CH2C6H5), 4.86 (d, 1H, J1,2
4.0, Hz, H-1), 5.15 (dd, 1H, J1,2 4.0, J2,3 9.4 Hz, H-2), 7.33 (m, 5H,
C6H5); 13C NMR (CDCl3, 75 MHz) δ 16.1 (CH3-6), 21.0 (CH3CO), 55.2 (1-
OCH3), 65.1 (C-5), 69.9 (C-4), 70.1 (C-2), 72.3 (CH2C6H5), 75.7 (C-3),
97.3 (C-1), 127.7, 128.0, 128.5, 137.8 (C6H5), 170.4 (CO); MS (ESI +):
m/z 311 [M+H]+; Anal. Calcd for C16H22O6: C, 61.92; H, 7.15. Found: C,
61.73; H, 7.33%.
4.3. General procedures for reductive ring-opening reactions of 4,6-O-
benzylidene acetals
All reactions were carried out under argon atmosphere and the
starting benzylidene acetals were co-evaporated with toluene and
placed under vacuum overnight. Reactions with BH3 were performed
without molecular sieves because the excess of reagent readily reacts
with any trace of water. Although TfOH can catalyse the ring-opening
Methyl 4-O-benzyl-2-O-methyl-
α
-L-fucopyranoside (9): viscous
and colorless liquid;
α
]
21 -101 (c 1.0, CHCl3), lit.12d
[
α
]
18 ꢀ 109 (c 1.92,
D
CHCl3); Rf 0.42 (hexane/EtOAc 4:6); IR (film)
ν
3475D, br (OH), 2925,
2830, 1493, 1461, 1357, 1099, 1046 cmꢀ 1; 1H NMR (CDCl3, 500 MHz) δ
1.21 (d, 3H, J5,6 6.6 Hz, CH3-6), 2.33 (d, 1H, J3,OH 5.1 Hz, 3-OH), 3.38 (s,
3H, 1-OCH3), 3.47 (s, 3H, 2-OCH3), 3.57 (dd, 1H, J1,2 3.7, J2,3 10.1 Hz,
H-2), 3.64 (dd, 1H, J3,4 3.3, J4,5 1.3 Hz, H-4), 3.90 (qd, 1H, J4,5 1.3, J5,6
6.6 Hz, H-5), 4.00 (m, 1H, J2,3 10.1, J3,4 3.3, J3,OH 5.1 Hz, H-3), 4.73,
4.86 (AB system, 2H, J ꢀ 11.5 Hz, CH2C6H5), 4.90 (d, 1H, J1,2 3.7, Hz, H-
1), 7.34 (m, 5H, C6H5); 13C NMR (CDCl3, 75 MHz) δ 16.7 (CH3-6), 55.3
(1-OCH3), 58.0 (2-OCH3), 66.0 (C-5), 70.5 (C-3), 75.6 (CH2C6H5), 78.6
(C-2), 79.4 (C-4), 97.1 (C-1), 127.8, 128.2, 128.4, 138.3 (C6H5); MS (ESI
+): m/z 283 [M+H]+; Anal. Calcd for C15H22O5: C, 63.81; H, 7.86.
Found: C, 63.70; H, 7.98%.
◦
polymerization of THF, at ꢀ 35 C and short reaction times only small
amounts of THF oligomers were found and could be easily separated by
flash chromatography. The substitution patterns of the benzyl ethers
formed were established based on the characteristic downfield shifts
observed in the 1H NMR spectra of the corresponding O-acetylated
derivatives.
Method A. A 1 M solution of BH3⋅THF complex in THF (2 mL) was
added to the corresponding benzylidene acetal (0.2 mmol) at the
selected temperature. After stirring for 10 min a 1 M solution of Bu2BOTf
in CH2Cl2 (0.2 mL) was added ([substrate] = 0.09 M) and the mixture
was stirred for the appropriate reaction time (Table 1). The reaction was
quenched at the chosen temperature with solid NaHCO3 followed by
dropwise addition of a saturated solution of NaHCO3 until effervescence
ceased. The mixture was allowed to reach room temperature, diluted
with CH2Cl2 and filtered through Celite. The organic layer was washed
successively with saturated solution of NaHCO3 and brine, dried and
Methyl 3-O-benzyl-2-O-methyl-
α
-L-fucopyranoside (10): viscous
and colorless liquid; [
4:6); IR (film)
α
]
21 ꢀ 106 (c 0.9, CHCl3); Rf 0.28 (hexane/EtOAc
D
ν
3482, br (OH), 2934, 2830, 1492, 1456, 1358, 1098,
1052 cmꢀ 1; 1H NMR (CDCl3, 300 MHz) δ 1.27 (d, 3H, J5,6 6.6 Hz, CH3-
6), 2.43 (s br, 1H, 4-OH), 3.39 (s, 3H, 1-OCH3), 3.52 (s, 3H, 2-OCH3),
3.60 (dd, 1H, J1,2 3.7, J2,3 11.0 Hz, H-2), 3.77 (m, 2H, H-3, H-4), 3.85
5

M. Studzian et al.
Carbohydrate Research 505 (2021) 108338
[2] (a) S. Lang, X. Huang, Carbohydrate conjugates in vaccine developments, Front.
Chem. 8 (2020) 284, https://doi.org/10.3389/fchem.2020.00284;
(b) R. Mettu, C.-Y. Chen, C.-Y. Wu, Synthetic carbohydrate-based vaccines:
challenges and opportunities, J. Biomed. Sci. 27 (2020) 9, https://doi.org/
10.1186/s12929-019-0591-0;
(qd, 1H, J4,5 1.3, J5,6 6.6 Hz, H-5), 4.65, 4.76 (AB system, 2H, J ꢀ 11.7
Hz, CH2C6H5), 4.83 (d, 1H, J1,2 3.7, Hz, H-1), 7.32 (m, 5H, C6H5); 13
C
NMR (CDCl3, 75 MHz) δ 16.1 (CH3-6), 55.2 (1-OCH3), 59.2 (2-OCH3),
65.1 (C-5), 70.3 (C-4), 72.6 (CH2C6H5), 77.7, 77.9 (C-2, C-3), 97.9 (C-1),
127.7, 127.8, 128.5, 138.3 (C6H5); MS (ESI +): m/z 283 [M+H]+; Anal.
Calcd for C15H22O5: C, 63.81; H, 7.86. Found: C, 63.94; H, 7.75%.
(c) F. Berti, R. Adamo, Antimicrobial glycoconjugate vaccines: an overview of
classic and modern approaches for protein modification, Chem. Soc. Rev. 47
(2018) 9015–9025, https://doi.org/10.1039/c8cs00495a.
Methyl 4-O-benzyl-2-O-ethyl-
α
-L-fucopyranoside (11): viscous
[3] (a) K.-T. Jin, H.-R. Lan, X.-Y. Chen, S.-B. Wang, X.-J. Ying, Y. Lin, X.-Z. Mou,
Recent advances in carbohydrate-based cancer vaccines, Biotechnol. Lett. 41
(2019) 641–650, https://doi.org/10.1007/s10529-019-02675-5;
(b) D. Feng, A.S. Shaikh, F. Wang, Recent advance in tumor-associated
carbohydrate antigens (TACAs)-based antitumor vaccines, ACS Chem. Biol. 11
(2016) 850–863, https://doi.org/10.1021/acschembio.6b00084;
(c) S.J. Danishefsky, J.A. Allen, From the laboratory to the clinic: a retrospective
on fully synthetic carbohydrate-based anticancer vaccines, Angew. Chem. Int. Ed.
39 (2000) 836–863, https://doi.org/10.1002/(sici)1521-3773(20000303)39:
5<836::aid-anie836>3.0.co;2-I.
21
and colorless liquid; [
α
]
ꢀ 99 (c 1.0, CHCl3); Rf 0.41 (hexane/EtOAc
D
3:7); IR (film)
ν 3477, br (OH), 2924, 2830, 1495, 1451, 1358, 1094,
1047 cmꢀ 1; 1H NMR (CDCl3, 500 MHz) δ 1.17 (d, 3H, J5,6 6.6 Hz, CH3-
6), 1.20a (3H, J 7.0 Hz, 2-OCH2CH3), 1.94 (s br, 1H, 3-OH), 3.37 (s, 3H,
1-OCH3), 3.57a (1H, J ꢀ 10.6, 7.0 Hz, 2-OCH2CH3), 3.64 (dd, 1H, J3,4
3.4, J4,5 1.5 Hz, H-4), 3.67 (dd, 1H, J1,2 3.6, J2,3 10.2 Hz, H-2), 3.70a (1H,
J ꢀ 10.6, 7.0 Hz, 2-OCH2CH3), 3.88 (qd, 1H, J4,5 1.5, J5,6 6.6 Hz, H-5),
3.99 (dd, 1H, J2,3 10.2, J3,4 3.4 Hz, H-3), 4.70, 4.88 (AB system, 2H, J
ꢀ 11.7 Hz, CH2C6H5), 4.83 (1H, d, J1,2 3.6, Hz, H-1), 7.34 (m, 5H, C6H5),
aABX3 system; 13C NMR (CDCl3, 125 MHz) δ 15.6 (2-OCH2CH3), 16.7
(CH3-6), 55.3 (1-OCH3), 65.9 (C-5), 66.0 (2-OCH2CH3), 70.5 (C-3), 75.4
(CH2C6H5), 77.1 (C-2), 79.1 (C-4), 97.8 (C-1), 127.7, 128.3, 128.6,
138.5 (C6H5); MS (ESI +): m/z 297 [M+H]+; Anal. Calcd for C16H24O5:
C, 64.84; H, 8.16. Found: C, 64.65; H, 8.37%.
´
´
[4] (a) P. Valverde, A. Arda, N.C. Reichardt, J. Jimenez-Barbero, A. Gimeno, Glycans
in drug discovery, Medchemcomm 10 (2019) 1678–1691, https://doi.org/
10.1039/c9md00292h;
(b) J. Shelton, X. Lu, J.A. Hollenbaugh, J.H. Cho, F. Amblard, R.F. Schinazi,
Metabolism, biochemical actions, and chemical synthesis of anticancer
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https://doi.org/10.1021/acs.chemrev.6b00209;
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pharmaceutical research, Chem. Eur J. 11 (2005) 3194–3206, https://doi.org/
10.1002/chem.200500025.
1,5-Anhydro-4-O-benzyl-2-O-methyl-L-fucitol (12): viscous and
colorless liquid; [
α
]
21 ꢀ 74 (c 1.0, CHCl3); Rf 0.32 (hexane/EtOAc 4:6);
[5] (a) T.V. Wang, A.V. Demchenko, Synthesis of carbohydrate building blocks via
regioselective uniform protection/deprotection strategies, Org. Biomol. Chem. 17
(2019) 4934–4950, https://doi.org/10.1039/c9ob00573k;
D
IR (film)
ν
3456, br (OH), 2934, 2827, 1494, 1451, 1357, 1092, 1048
cmꢀ 1; 1H NMR (CDCl3, 500 MHz) δ 1.22 (d, 3H, J5,6 6.4 Hz, CH3-6), 2.35
(d, 1H, J3,OH 5.7 Hz, 3-OH), 3.05 (tap, 1H, J1ax,1ec ꢀ 11.1, J1ax,2 10.0, H-
1ax), 3.44 (s, 3H, 2-OCH3), 3.48a (m, 1H, H-5), 3.50a (tdap, 1H, J1ax,2
10.0, J1ec,2 4.9, J2,3 9.5 Hz, H-2), 3.59 (m, 1H, H-3), 3.61 (s br, 1H, H-4),
4.11 (dd, 1H, J1ax,1ec ꢀ 11.1, J1ec,2 4.9 Hz, H-1ec), 4.74, 4.80 (AB system,
(b) J. Janssens, M.D.P. Risseeuw, J. Van der Eycken, S. Van Calenbergh,
Regioselective ring opening of 1,3-dioxane-type acetals in carbohydrates, Eur. J.
Org Chem. (2018) 6405–6431, https://doi.org/10.1002/ejoc.201801245;
(c) V. Dimakos, M.S. Taylor, Site-selective functionalization of hydroxyl groups in
carbohydrate derivatives, Chem. Rev. 118 (2018) 11457–11517, https://doi.org/
10.1021/acs.chemrev.8b00442;
2H, J ꢀ 11.7 Hz, CH2C6H5), 7.34 (m, 5H, C6H5), a overlapped signals; 13
C
(d) J. Lawandi, S. Rocheleau, N. Moitessier, Regioselective acylation, alkylation,
silylation and glycosylation of monosaccharides, Tetrahedron 72 (2016)
6283–6319, https://doi.org/10.1016/j.tet.2016.08.019.
NMR (CDCl3,75 MHz) δ 17.2 (CH3-6), 29.7(C-1), 58.3 (2-OCH3), 67.3 (C-
5), 70.6 (C-3), 75.8 (CH2C6H5), 77.2 (C-2), 79.4 (C-4), 127.5, 128.2,
128.6, 138.6 (C6H5); MS (ESI +): m/z 253 [M+H]+; Anal. Calcd for
´ ´
´
[6] (a) M. Herczeg, L. Lazar, M. Ohlin, A. Borbas, Regioselective reductive openings of
4,6-O-benzylidene-type acetals using LiAlH4-AlCl3, in: G. van der Marvel, J. Codee
(Eds.), Carbohydrate Chemistry: Proven Synthetic Methods, CRS Press, Boca Raton,
2014, pp. 9–19, https://doi.org/10.1201/b16602;
C
14H20O4: C, 66.65; H, 7.99. Found: C, 66.35; H, 8.17%.
´
´
´
(b) D. Szikra, A. Mandi, A. Borbas, I.P. Nagy, I. Komaromi, A. Kiss-Szikszai,
M. Herczeg, S. Antus, A kinetic study on the reductive opening of methyl 2,3-O-
Declaration of competing interest
diphenylmethylene-α-L-rhamnopyranoside, Carbohydr. Res. 346 (2011)
2004–2006, https://doi.org/10.1016/j.carres.2011.04.041;
´
´
´
´
(c) A. Mandi, I. Komaromi, A. Borbas, D. Szikra, I.P. Nagy, A. Liptak, S. Antus,
The authors declare that they have no known competing financial
interests or personal relationships that could have appeared to influence
the work reported in this paper.
Quantum chemical studies on the partial hydrogenolysis of methyl 2,3-O-
diphenylmethylene-α-L-rhamnopyranoside, Tetrahedron Lett. 52 (2011)
1256–1259, https://doi.org/10.1016/j.tetlet.2011.01.021;
´
´
´
´ ´
(d) Z. Jakah, A. Mandi, A. Borbas, A. Benyei, I. Komaromi, L. Lazar, S. Antus,
´
A. Liptak, Synthesis, regioselective hydrogenolysis, partial hydrogenation, and
Acknowledgments
conformational study of dioxane and dioxolane-type (9’-anthracenyl)methylene
acetals of sugars, Carbohydr. Res. 344 (2009) 2444–2453, https://doi.org/
10.1016/j.carres.2009.09.007;
´
This research has received funding from Universidad de Alcala
´
´
(e) Z.B. Szako, A. Borbas, I. Bajza, A. Liptak, Synthesis of fully protected α-l-
(UAH, Projects CCG2016/EXP-044, and CCG2017/EXP-019).
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