Lewis acid promoted anomerisation of alkyl O- and S-xylo-, arabino- and fucopyranosides

Article abstract of DOI:10.1016/j.carres.2018.11.010

Pentopyranoside and 6-deoxyhexopyranosides, such as those from D-xylose, L-arabinose and L-fucose are components of natural products, oligosaccharides or polysaccharides. Lewis acid promoted anomerisation of some of their alkyl O- and S-glycopyranosides i

Full text of DOI:10.1016/j.carres.2018.11.010

Accepted Manuscript
Lewis acid promoted anomerisation of alkyl O- and S-xylo-, arabino- and
fucopyranosides
Lisa M. Doyle, Fiach Meany, Paul V. Murphy
PII:
S0008-6215(18)30604-9
https://doi.org/10.1016/j.carres.2018.11.010
CAR 7634
DOI:
Reference:
To appear in: Carbohydrate Research
Received Date: 15 October 2018
Revised Date: 20 November 2018
Accepted Date: 20 November 2018
Please cite this article as: L.M. Doyle, F. Meany, P.V. Murphy, Lewis acid promoted anomerisation
of alkyl O- and S-xylo-, arabino- and fucopyranosides, Carbohydrate Research (2018), doi: https://
doi.org/10.1016/j.carres.2018.11.010.
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ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
Lewis Acid Promoted Anomerisation of Alkyl O- and S-Xylo-, Arabino-
and Fucopyranosides
Lisa M. Doyle, Fiach Meany and Paul V. Murphy*
School of Chemistry, National University of Ireland Galway, University Road, Galway,
Ireland, H91 TK33
Email: paul.v.murphy@nuigalway.ie
Abstract: Pentopyranoside and 6-deoxyhexopyranosides, such as those from D-xylose,
L-
arabinose and
L-fucose are components of natural products, oligosaccharides or
polysaccharides. Lewis acid promoted anomerisation of some of their alkyl O- and S-
glycopyranosides is reported here. SnCl4 was more successful than TiCl4, with the latter
giving glycosyl chloride in some cases, and both were reactive than BF3OEt2. Kinetic study
1
using H-NMR spectroscopy showed an order of reactivity: O-xylopyranoside > O-
arabinopyranoside > O-fucopyranoside. Benzoylated glycosides were more reactive than
acetylated glycosides. The reactivity of S-glycosides was greater than that of O-glycosides
for both arabinose and fucose derivatives; reactivity of O- and S-xylopyranosides was similar.
The highest stereoselectivities were observed for fucopyranosides. The β-
and α- -arabinopyranoside reactants are conformationally more flexible than β-
fucopyranosides.
D-xylopyranoside
L
L-
1

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1. Introduction
The chemical reactivity of saccharides is influenced by their substituents.1 For instance,
whether a substituent is axial or equatorial on a pyranoside influences the rate of hydrolysis
of the glycosidic linkage, with reactivity increasing if there are more axial OH groups
present.1a The degree to which substituents are electron withdrawing influences glycosyl
donor reactivity. Accordingly, it was established that presence of O-acyl substituents reduce
reactivity of donors compared to O-benzyl substituents.2 Substituents also influence the
kinetics of anomerisation of O- and S-glycosides promoted by Lewis acids3 and also
influence anomeric preference in these reactions, which are presumed to be at equilibrium.4
Lewis acid promoted anomerisation5 has been used for the stereoselective synthesis of
glycosides,6 but specific strategies are required to achieve success. For instance, the use of
both 2,3-trans-carbamate and carbonate based protecting groups on pyranosides,7 gives rise to
4
a slight distortion in their C1 conformations, which leads to an enhancement of the rate of
anomerisation via endocyclic cleavage.8 Alternatively, a CO2R substituent at C-5, as found
in glucuronic and galacturonic acid derivatives, coupled with the use of benzoyl protecting
groups at other positions9 enabled TiCl4 induced anomerisation of the interglycosidic linkage
in disaccharides and other linkages.10,11 It was proposed in the latter case that the C-5
carbonyl group facilitates chelation by Lewis acids such as TiCl4 or SnCl4 and subsequent
endocyclic cleavage (Scheme 1).12 This chelation renders anomerisation of the uronic acids
more efficient than for benzoylated gluco- and galactopyranosides.12 Chelation, however, is
not ruled out for (acylated) gluco- and galactopyranosides given they contain oxygen atoms
at C-6 that can potentially chelate. Anomerisation can also proceed through an exocyclic
cleavage pathway (Scheme 1).
2

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The main aim of this study was to investigate the potential usefulness of anomerisation in
generating α-xylopyranosides, β-arabinopyranosides and α-fucopyranosides.
These
saccharides lack any C-5 chelating substituent, and was also considered of interest to
compare their reactivity to that of other saccharides studied to date.3 Aside from our recent
study on glycosyl thiols,13 there has not been a systematic study of Lewis acid anomerisation
of these saccharides, that we are aware of.
Mammalian glycans that contain α-L-
fucopyranosides are involved in interactions between host cells and microorganisms, blood
transfusion reactions, leukocyte adhesion and numerous ontogenic events.14 The 1,2-cis
linked fucopyranoside15 is present in glycans such as blood group antigens A, B and H,
Lewisb, Lewisy, sialyl Lewisx and globo-H and α- -fucosidases are of interest in biomedice.16
L
β-
arabinopyranosidase has been identified.17 The chemistry of xylopyranosides has been
reviewed18,19 and α-
L-Arabinopyranose is
a
component of arabinogalactan-proteins and
a
β-L-
D
-xylopyranoside has been found on the non-reducing terminal of the
backbone of oligoxyloglucans, such as in the disaccharide isoprimeverose. α-Xylosidases
and functions associated with them have been identified.20
Scheme 1: Possible pathways for Lewis acid promoted O-glycoside anomerisation through (a)
exocyclic or (b) endocyclic cleavage. Endocyclic cleavage may be promoted by chelation. The
reactants investigated herein (X = O, S) lack chelating substituents at C-5.
3

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Results and Discussion
2.1
Synthesis of O- and S-glycosides for anomerisation study
Butyl O- and S-glycosides, which are acetylated or benzoylated (Chart 1), were first
synthesised (Scheme 2) so that reactivity and stereoselectivity comparisons could be
compared with glycosides studied previously.4,21 Acetyl and benzoyl groups were chosen as
protecting groups as they are stable to SnCl4 and TiCl4 and they influence reactivity and
stereoselectivity. Briefly, O-glycosides (1-2β, 3-4α, 5-6β and 12β-13β) were prepared from
the corresponding glycosyl bromide precursor according to the glycosylation method
involving I2 and DDQ as reported by Lehmler and co-workers.22 The 1,2-trans anomer was
generally obtained and the yields varied from 27-76%. The S-glycosides 7β-10β were
prepared via the appropriate glycosyl thiol, which was reacted with DIPEA and iodobutane to
give the S-butyl glycosides (67-83%). Glycoside 11β was prepared as described previously.13
Scheme 2 Summary of the synthesis of O-glycosides and S-glycosides
4

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Chart 1 Structures of O- and S-glycosides. The yields from the glycosyl bromide are given
in the case of the O-glycosides and from the thiol for the S-glycosides.
2.2
Behaviour of O- and S-glycosides towards TiCl4, SnCl4 and BF3OEt2.
The TiCl4 promoted reaction of xylopyranoside 2β (Table 1) led only to the formation of a
mixture of glycosyl chlorides 14 and 1523 (entry 1). Carrying out this reaction at lower
temperature led to only 2β being recovered (entry 2), while reducing the reaction time (entry
3) to 2 h at room temperature also led to mostly recovered 2β. In contrast, the use of SnCl4
(2.5 equiv) at room temperature gave a mixture of anomers where 2α (entry 4) predominated
after 24 h. Decreasing the temperature reduced glycosyl chloride formation while still giving
2α (entry 6).
The SnCl4 (2.5 equiv) promoted reactions of equatorial O-glycosides 1 and 3-6 also
1
gave the axial O-glycoside as the major product, as determined by H-NMR spectroscopic
analysis of the product mixture after work-up (>85% yield), with the original reactant being
the other main component (Table 2). For SnCl4 and 1β, the use of reaction temperatures of -
30 °C and 4 °C, like that of 2β, gave slightly higher axial:equatorial ratios when compared to
reaction at 20 °C. In contrast, reaction of arabinopyranosides and fucopyranosides 3-6 led to
lower amounts of the axial anomer on lowering the reaction temperature to 4 °C or -30 °C.
5

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This is likely due to reduced reaction rates for 3-6 compared to 1 or 2 (vide infra). In contrast
with the findings for 2β (Table 1) the use of TiCl4 did give axial anomers for 1β and 3β, 4β
and 6β. However the stereoselectivities/yields were generally lower than that observed for
SnCl4 and, in the case of 4 and 6, glycosyl chloride formation predominated at 20 °C.
Table 1 Effect of Lewis acid and temperature on reactions of xylopyranoside 2βa
Entry Time
Temp.
Lewis acid Equivalents
%2α
%2β
%14
%15
1
2
24 h
24 h
20 °C
2.5
2.5
<2
4
35
60
TiCl₄
TiCl₄
4 °C
<2
>94
<2
<4
3
4
2 h
2.5
2.5
<2
74
80
22
<2
<2
20
4
TiCl₄
SnCl₄
20
20
4
°
°
C
C
24 h
5
6
7
24 h
24 h
24 h
2.5
2.5
5
68
80
78
24
20
18
<2
<2
2
6
SnCl₄
SnCl₄
SnCl₄
°
C
<4
<4
-30
°
C
20
°
C
aProduct ratios were determined by 1H-NMR spectroscopic analysis of product mixtures after
work-up.
6

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a
Table 2 SnCl4 (0.5 equiv) promoted anomerisation reactions of 1β-6β in CH2Cl2
Entry Reactant Temp.
α:β
1
2
-30 °C
4 °C
88:12
1β
1β
84:16
3
4
5
6
7
77:23
80:20
78:22
75:25
41:59
20 °C
1β
2β
2β
2β
3β
-30 °C
4 °C
20 °C
-30 °C
4 °C
8
75:25
79:21
56:44
72:28
79:21
8:92
3β
3β
4β
4β
4β
5β
5β
5β
6β
6β
6β
9
20 °C
10
11
12
13
14
15
16
17
18
-30 °C
4 °C
20 °C
-30 °C
4 °C
48:52
78:22
4:96
20 °C
-30 °C
4 °C
28:72
80:20
20 °C
1
aThe proportion of α-anomer was determined after 24 h by H NMR spectroscopy. These
experiments reported were carried out once.
7

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The anomerisation of S-glycosides 8-10 was next investigated. SnCl4 was found to work best
at 20 °C, whereas at this temperature, the use of TiCl4 led to formation of glycosyl chlorides.
The stereoselectivity after 24 h, was generally lower in S-glycoside anomerisation than for
the corresponding O-glycoside (see Table 3). This is related to factors which influence
relative stability of anomers such as the endo-anomeric effect as well as intramolecular steric
and repulsive and Coulombic interactions. Unlike the glycosyl thiols, which epimerised to
the equatorial thiol with SnCl4, these S-glycosides gave the axial anomer preferentially.
Boron trifluoride etherate was investigated as an alternative Lewis acid, but was unable to
promote useful anomerisation for butyl glycosides. In the reaction of 6β it gave a complex
mixture with a trace of 6α detected by NMR spectroscopy. Only in the case of isopropyl
glycosides, which are more significantly reactive than butyl glycosides (see Table 3), could
useful anomerisation be observed with BF3ñOEt2 (0.5 equiv); thus the reaction of this Lewis
acid with 13β gave a 4:1 mixture of 13α and 13β after 24 h.
2.3
Conformational analysis
The conformations of the pyranosides may be expected to influence reactivity. Ellervik and
colleagues have reviewed xylopyranosides, including their conformational preferences. In
3
the case of methyl β-
D
-xylopyranoside the JH1,H2 = 7.8 Hz and was regarded as being
consistent with adoption of the 4C1 conformation exclusively. Deviation from this and other
couplings, towards lower values is diagnostic of conformational change. The observed J-
1
values for ring protons on the xylopyranosides were measured in the H-NMR spectra
recorded at 500 MHz in CDCl3 (see experimental section or Table S1 in the supporting
information). For the β-anomers of the O-xylopyranosides, the 3JH1,H2 value was consistently
less than 7.8 Hz, which indicates that the 1C4 conformation is populated.24 This population of
1C4 is higher for benzoylated O-xylopyranosides (for 2β 3JH1,H2 = 5.3 Hz; for 13β 3JH1,H2 = 5.5
8

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3
3
Hz) than for acetylated counterparts (for 1β JH1,H2 = 6.8 Hz; for 12β JH1,H2 = 7.0 Hz).
Comparison of J-values for 1β with those reported for methyl 2,3,4-tri-
Ο-acetyl-β-D-
xylopyranoside in CDCl3 show they are in excellent agreement and consistent with a
4
1
population of the C1 conformer of >80%, with C4 conformer at <20%.25 In contrast, the J
4
values for the benzoylated 2β indicates there is a population of ~60% of C1 conformer and
1
3
~40% C4. While the JH1,H2 for the S-glycosides is higher than the corresponding O-
1
glycoside, the examination of the other ring coupling constants indicate that their C4
conformer is also populated, with evidence of a higher population again for the benzoylated
structure 8β compared to the acetylated 7β.
All the α-xylopyranosides have higher
4
preferences for the C1 conformer compared to the β-anomers. Examination of the J values
for the arabinopyranosides (see experimental section or Table S2 in supporting information)
and comparison with a published conformational analysis for methyl arabinopyranosides26
1
4
indicate that their α-anomers can also adopt the C4 conformer with the C1 population
decreasing from ~80% for 3α compared to <70% for the benzoylated 4. In contrast, the β-L-
fucosides adopt predominantly the 1C4 conformers, supported, for example, by 3JH1,H2 values
which are consistently ~8.0 Hz.
2.3
Kinetics of SnCl4 promoted anomerisation and mechanistic considerations
The reactivity of 1-11 towards SnCl4 (0.5 equiv) in CDCl3 was established by NMR
spectroscopy as previously described.3 Concentrations of equatorial glycosides and the
products were monitored with time and the data obtained was fitted with the equation27 for
equilibrium kinetics:
ꢁ ꢂ ꢁ ꢂ
A – A
ꢃ
ꢄ
ꢇ
ꢋ
ln ꢀ
ꢆ = − ꢈꢉ + ꢈꢊ t
ꢁ ꢂ ꢁ ꢂ
A – A
ꢅ
ꢄ
9

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The isolated yields of the products after work-up, and before chromatographic separations
were carried out, varied between 85-96%. The kf + kr values obtained from linear plots
generated using the equation above are given in Table 3; the coefficients of determination
(R2) values varied from 0.929 to 0.999. The relative kf + kr values, where comparisons are
made to the slowest reactant, i.e. the fucopyranoside 5β, is provided in Table 3. Also
included in the study was glucopyranoside 11β, so that comparisons could be made with it.
The kf + kr for 11β measured herein (14.5 x 10-6 s-1) in CDCl3 pre-distilled from P2O5, when
using 0.5 equivalent of SnCl4 is comparable that observed previously under similar
conditions (19 x 10-6 s-1) reported by Pilgrim and Murphy.3
The α:β ratios (Table 3) in the final product mixtures were not as high for reactions of 1-10
compared to reaction of the O-glucopyranoside 11β (16:1).16 The highest stereoselectivity
was 5.6:1 in favour of the axial anomer of the benzoylated O-fucopyranoside 6. Hence, the
absence of an electron withdrawing oxygen atom on the substituent at C-5 leads to a
reduction in axial anomer preference. Recent work with uronic acids, for example,
comparing them with glucopyranose or galactopyranose, shows that a more electron
withdrawing C-5 substituent gives rise to increased axial anomer preference when
equilibration is possible.4, 28
Benzoylated glycosides underwent anomerisation ~1.3 to 3.3 times faster than their
acetylated counterparts (c.f. entries 2 vs 1, 4 vs 3, 6 vs 5, 8 vs 7). This is consistent with data
acquired for 11β when compared to the reactivity of its acetylated counterpart, although it is
not clear if this is for similar reasons.3 From work on glucopyranosides, which are
conformationally rigid, there is a benefit from having a benzoyl group at C-2, compared to an
acetyl group.21 This may indicate there is a role for the 2-O-benzoyl group in stabilising a
carbocation intermediate, generated during the course of the reaction, through resonance.
Benzoyl groups may normally be expected to reduce reactivity towards anomerisation
10

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through inductive or field effects as they are more electron withdrawing than acetates (pKa
benzoic acid = 4.20 vs pKa acetic acid = 4.76). In the case of xylopyranoside and
arabinopyranoside, the presence of benzoyl groups increase the population of the axial rich
conformer (1C4) but there is no evidence for similar behaviour for the fucopyranosides.
One interesting observation is that the xylopyranoside 2β (entry 2) was about 1.6 fold
faster than glucopyranoside 11β (entry 11) even though the xylopyranoside lacks the
chelating substituent at C-5, present in glucopyranoside. This questions the necessity of
chelation, involving the ring oxygen and C-5 substituent. However, the C-5 substituent in
glucopyranose is electron withdrawing and its absence leads to a more electron rich pyranose
ring, which could partially explain the increased reactivity of xylopyranoside, compensating
for any benefit that would arise from having a chelating substituent. That the isopropyl
glycoside 13β was faster than the corresponding butyl glycoside 2 is consistent with greater
electron releasing properties of the isopropyl group, compared to the butyl group.
Table 3 Kinetic data and product ratios for SnCl4-promoted anomerisation. Yields were
>85% in each reaction.
Entry
Reactant
Axial Product 106(kf +kr) Relative
Anomeric ratio
(axial:equatorial)
(s-1)
kf +kr
1
17
8.9
3.4:1
3.5:1
2
3
23.5
3.7
12.4
1.9
3.6:1
3.7:1
4
11.3
5.9
11

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5
6
7
8
9
1.9
1.0
1.5
4.3:1
5.6:1
1.4:1
1.7:1
2:1
OBu
OBz
O
2.8
OBz
BzO
6
17.3
20.4
41.4
9.1
10.7
21.8
10
11
33.2
14.5
17.5
7.6
2:1
16:1
12
555
292
7.5:1
4
The O-fucopyranosides with an axial C-4 substituent in their C1 conformers, but with a
methyl substituent instead of hydrogen at C-5, underwent anomerisation more slowly than
arabinopyranosides (c.f. entries 3 with 5 and 4 with 6). The higher stereoselectivity found for
fucopyranosides (c.f. entries 5 vs 3/1; c.f. 6 vs 4/2) compared to xylopyranosides and
arabinopyranosides may be due to the C-5 methyl substituent, being more electron donating
than a hydrogen atom, increasing electron density on the pyranose oxygen atom and
increasing the endoanomeric effect. Interestingly, the D-xylopyranosides, if considering all
4
equatorial substituents in their C1 conformer, are more reactive than the corresponding L-
12

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4
arabinopyranosides, the latter having one axial C-4 substituent in their C1 conformers (c.f.
entries 1 with 3 and 2 with 4).
In the earlier study based on glucopyranosides/galactopyranosides and related uronic acids
the S-glycosides were generally faster than the corresponding O-glycosides. Herein, the S-
fucopyranoside 10β was an order of magnitude faster than O-fucopyranoside 6β whereas S-
arabinopyranoside 9α was ~ 3fold faster than O-arabinopyranoside 4α. This can be
explained due to sulfur being more electron releasing than oxygen and hence better able to
stabilise the carbocation generated by endocyclic cleavage. In the acid catalysed hydrolysis
of S- and O-glycosides, which proceed by exocyclic cleavage, the O-glycosides cleave
faster.29 Here, the S-xylopyranoside 8β reacted slightly more slowly than its O-glycoside
counterpart 2β (compare entries 1 vs 8) whereas the O-xylopyranoside 7β had a similar
reaction rate as the thioglycoside 1β.
The kinetic data could indicate that anomerisation in the xylopyranosides involves exocyclic
cleavage whereas those of fucopyranosides and arabinopyranosides involve endocyclic
cleavage. To investigate this in xylopyranoside, a crossover experiment was attempted.
Thus, the xylosides 1β and 13β were mixed at the same concentrations as investigated for the
kinetics experiments in an NMR tube and SnCl4 (0.5 equiv) was added in CDCl3 and the
reaction monitored by NMR. While anomerisation of the mixture of 1β and 13β gave both
1α and 13α after a few hours, as well as remaining reactants, it was only after 24 h that the
crossover products 2α and 12α (each ~ 5%) could be seen; these were evidenced by the
appearance of broad signals at δ 5.14 for 12α and at δ 5.27 for 2α in accordance with those
signals observed in standard samples of 2α/12α prepared herein. At 24 h, the ratios of 1α :
13α : 1β : 13β : 2α : 12α in the crossover reaction mixture was 30 : 30 : 12.5 : 12.5 : 5 : 5.
The relative amount of crossover product did continue to increase after 24 h. It was found to
be much higher if 10-fold higher concentrations of SnCl4 was used. But the latter experiment
13

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also gave a more complex mixture and the conditions are very different to those where the
kinetics were measured. Thus, anomerisation via crossover can take place, possibly via
exocyclic cleavage, but it is slow relative to the intramolecular anomerisation. However,
slow crossover or lack of crossover can still be explained by an exocyclic cleavage pathway
which gives anomerisation predominantly via intimate ion pairs and thus results from the
crossover could not conclusively rule out exocyclic cleavage.30 In previous work from our
laboratory on glucopyranosides and galactopyranosides,4 the outcome of trapping
experiments31 supported also the occurrence of endocyclic cleavage for the SnCl4 catalysed
anomerisation, although it was not possible to get such evidence as part of this study.
2.7
Conclusions
The Lewis acid catalyzed anomerization reactions of
D-xylo-, L-arabino- and L-
fucopyranosides have been studied, providing a basis for investigating new applications of
the reaction. The reactivity order is xylopyranoside > arabinopyranoside > fucopyranoside
and this coincides with the relative conformational flexibility of these pyranosides. This
1
correspondence could be interpreted as the C4 conformers of xylopyranosides and
arabinopyranosides being more susceptible to SnCl4 promoted endocyclic cleavage, than
fucopyranosides. This hypothesis would need to be supported by more extensive study.
However, it has been shown both in glycoside hydrolysis1a and glycosylation32 that
saccharide reactivity is increased when axial rich conformers have increased population. It is
clear that chelation of SnCl4 to a substituent at C-5 of a pyranoside is not required for
anomerisation to proceed.
Experimental Section
14

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General Experimental Procedures NMR spectra were recorded (25 °C) with a 500 MHz
Agilent spectrometer. Data are reported in the following order: chemical shift (δ) in ppm;
multiplicities indicated as s (singlet), d (doublet), t (triplet), q (quartet), m (multiplet);
coupling constants (J) given in Hertz (Hz). Chemical shifts are reported relative to internal
standard Me4Si in CDCl3 (d 0.0) for 1H and CDCl3 (d 77.0) for 13C. 1H NMR spectral signals
13
were assigned with the aid of COSY, C NMR spectral signals using DEPT, gHSQCAD
and/or gHMBCAD. NMR data for known compounds was in good agreement with
previously published data. High resolution mass spectra were measured in positive and/or
negative mode as indicated using a Waters LCT Mass Spectrometer. TLC was performed on
aluminium sheets precoated with silica gel and spots visualized by UV and charring with
H2SO4-EtOH (1:20) or cerium molybdate, unless otherwise stated. Chromatography was
carried out with silica gel 60 (0.040-0.630 mm) and using a stepwise solvent polarity gradient
correlated with TLC mobility, unless otherwise stated. CH2Cl2, MeOH, toluene and THF
reaction solvents were used as obtained from a Pure Solv™ Solvent Purification System.
Optical rotations were determined at the sodium D line at 20°C using a Schmidt and Haensch
UniPol L1000. The IR spectra were recorded using thin film with a PerkinElmer Spectrum
100 FT-IR Spectrometer with an ATR attachment. Unless otherwise noted, all commercially
available compounds were used as obtained from suppliers without further purification.
Butyl 2,3,4-tri-O-acetyl-β-D-xylopyranoside 1β 2,3,4-Tri-O-acetyl-β-xylopyranosyl
bromide33 (7.1 g, 20.9 mmol) was added, under nitrogen, to I2 (5.31 g, 20.9 mmol), DDQ
(2.37 g, 10.5 mmol), n-butanol (3.83 mL, 41.9 mmol) and 4Å molecular sieves in anhydrous
CH2Cl2 (12 mL). The mixture was stirred at room temperature for 4.5 h, and it was then
filtered through celite, washed with Na2S2O3 (2% w/v), satd aq NaHCO3 and then brine. The
colourless organic layer was dried over Na2SO4, filtered and the solvent was removed under
15

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reduced pressure. Chromatography (cyclohexane-EtOAc, 4:1) gave the title compound (white
1
solid, 2.62 g, 38%); Rf 0.32 (cyclohexane-EtOAc, 4:1); ꢁαꢂꢍꢌꢃ -56 (c 1.0, CHCl3); H NMR
(500 MHz, CDCl3) δ 5.16 (t, J = 8.6 Hz, 1H, H-3), 4.98-4.89 (overlapping signals, 2H, H-2
and H-4), 4.46 (d, J = 6.8 Hz, 1H, H-1), 4.12 (dd, J = 11.8, 5.1 Hz, 1H, H-5a), 3.82 (dt, J =
9.6, 6.4 Hz, 1H, OCHH), 3.46 (dt, J = 9.6, 6.6 Hz, 1H, OCHH), 3.36 (dd, J = 11.8, 8.8 Hz,
1H, H-5b), 2.05 (s, 3H, C(O)CH3), 2.05 (s, 3H, C(O)CH3), 2.04 (s, 3H, C(O)CH3), 1.59–1.51
(overlapping signals, 2H, OCH2CH2), 1.40–1.30 (overlapping signals, 2H, O(CH2)CH2), 0.91
13
(t, J = 7.4 Hz, 3H, CH3); C NMR (126 MHz, CDCl3) δ 170.1, 169.8, 169.4 (each C=O),
100.7 (C-1), 71.5 (C-3), 70.9 (C-4), 69.4 (C-5), 68.9 (C-2), 62.0 (OCH2), 31.4 (OCH2CH2),
20.8, 20.7, 20.7 (each C(O)CH3), 19.0 (O(CH2)CH2), 13.7 (CH3); IR (ATR) cm-1: 2937,
1737, 1368, 1222, 1077, 1056; ESI-HRMS calcd for C15H24O8Na 355.1369, found m/z
355.1370 [M+Na]+.
Butyl 2,3,4-tri-O-benzoyl-β-D-xylopyranoside 2β The reaction of 2,3,4-tri-O-benzoyl-α-D-
xylopyranosyl bromide13 (1.14 g, 2.17 mmol), I2 (0.55 g, 2.17 mmol), DDQ (0.25 g, 1.09
mmol) and n-butanol (0.39 mL, 4.34 mmol) as described for the preparation of 1β, gave, after
chromatography (cyclohexane-EtOAc 7:1), the title compound as a crystalline solid.
Recrystallization from ethanol gave white crystals (0.49 g, 44%); Rf 0.32 (cyclohexane-
1
EtOAc 7:1); ꢁαꢂꢍꢌꢃ -29.8 (c 1.0, CHCl3); H NMR (500 MHz, CDCl3) δ 8.03-7.97
(overlapping signals, 6H, Ar-H), 7.56-7.49 (overlapping signals, 3H, Ar-H), 7.41-7.33
(overlapping signals, 6H, Ar-H), 5.74 (t, J = 7.1 Hz, 1H, H-3), 5.36 (dd, J = 7.1, 5.3 Hz, 1H,
H-2), 5.29 (td, J = 6.9, 4.2 Hz, 1H, H-4), 4.82 (d, J = 5.2 Hz, 1H, H-1), 4.43 (dd, J = 12.1, 4.2
Hz, 1H, H-5a), 3.88 (dt, J = 9.5, 6.3 Hz, 1H, OCHH), 3.71 (dd, J = 12.2, 6.9 Hz, 1H, H-5b),
3.53 (dt, J = 9.5, 6.5 Hz, 1H, OCHH), 1.61-1.55 (overlapping signals, 2H, OCH2CH2), 1.33
(dt, J = 14.8, 7.4 Hz, 2H, O(CH2)2CH2), 0.83 (t, J = 7.4 Hz, 3H, CH3); 13C NMR (126 MHz,
16

ACCEPTED MANUSCRIPT
CDCl3) δ 133.3, 133.3, 133.2 (each C=O), 129.9, 129.8, 128.4, 128.3, 128.3 (Ar-C and CH),
100.0 (C-1), 70.3 (C-2), 70.2 (C-3), 69.2 (C-4), 69.1 (C-5), 61.1 (OCH2), 31.6 (OCH2CH2),
19.1 (O(CH2)2CH2), 13.7 (CH3); IR (ATR) cm-1: 1708, 1604, 1457, 1256, 1072, 1030, 712,
688; ESI-HRMS calcd for C30H30O8Na 541.1838, found m/z 541.1833 [M+Na]+.
Butyl 2,3,4-tri-O-acetyl-α-L-arabinopyranoside 3α
Reaction of 2,3,4-tri-O-acetyl-β-
L
-arabinopyranosyl bromide34 (1.2 g, 3.5 mmol), I2 (0.90 g, 3.35 mmol), DDQ (0.40 g, 1.8
mmol) and n-butanol (0.65 mL, 7.08 mmol) in dry CH2Cl2 (11.0 mL) as described for the
preparation of 1β, gave, after chromatography (cyclohexane-EtOAc 3:2), the title compound
as a yellow oil (0.45 g, 61%); Rf 0.29 (cyclohexane-EtOAc 3:2); ꢁαꢂꢍꢌꢃ +4.93 (c 1.0, CHCl3);
1H NMR (500 MHz, CDCl3) δ 5.26 (td, J = 3.4, 1.8 Hz, 1H, H-4), 5.18 (dd, J = 9.4, 6.9 Hz,
1H, H-2), 5.04 (dd, J = 9.4, 3.5 Hz, 1H, H-3), 4.40 (d, J = 6.8 Hz, 1H, H-1), 4.03 (dd, J =
13.0, 3.4 Hz, 1H, H-5a), 3.86 (dt, J = 9.6, 6.3 Hz, 1H, OCHH), 3.62 (dd, J = 13.0, 1.8 Hz, 1H,
H-5b), 3.46 (dt, J = 9.6, 6.7 Hz, 1H. OCHH), 2.13 (s, 3H, C(O)CH3), 2.06 (s, 3H, C(O)CH3),
2.03 (s, 3H, C(O)CH3), 1.58-1.52 (overlapping signals, 2H, OCH2CH2), 1.41-1.33
13
(overlapping signals, 2H, O(CH2)CH2), 0.91 (t, J = 7.4 Hz, 3H, CH3); C NMR (126 MHz,
CDCl3) δ 170.4, 170.2, 169.4 (C=O), 101.0 (C-1), 70.2 (C-3), 69.5 (C-2), 69.3 (C-5), 67.7 (C-
4), 63.1 (OCH2), 31.5 (OCH2CH2), 21.0, 20.8, 20.7 (each C(O)CH3), 19.1 (O(CH2)CH2), 13.8
(CH3); IR cm-1: 2960, 1741, 1369, 1222, 1048, 1020; ES-HRMS calcd for C15H24O8Na
355.1369, found m/z 355.1368 [M+Na]+.
Butyl 2,3,4-tri-O-benzoyl-α-L-arabinopyranoside 4α
Reaction of 2,3,4-tri-O-benzoyl-
α-
L
-arabinopyranosyl bromide13 (0.13 g, 0.03 mmol) was added to I2 (0.06 g, 0.25 mmol),
DDQ (0.025g, 0.125 mmol) and n-butanol (0.045 mL, 0.125 mmol) in dry CH2Cl2 (0.5 mL)
as described for the preparation of 1β, gave, after chromatography (cyclohexane-EtOAc 4:1),
17

ACCEPTED MANUSCRIPT
the title compound (0.09 g, 72%) as a white powder: Rf 0.26 (cyclohexane-EtOAc 4:1); ꢁαꢂꢌꢍꢃ
1
+155.7 (c 1.0, CHCl3); H NMR (500 MHz, CDCl3) δ 8.06-8.00 (overlapping signals, 4H,
Ar-H), 7.96-7.93 (overlapping signals, 2H, Ar-H), 7.59-7.52 (overlapping signals, 2H, Ar-H),
7.51-7.47 (m, 1H, Ar-H), 7.46-7.40 (overlapping signals, 4H, Ar-H), 7.36-7.31 (overlapping
signals, 3H, Ar-H), 5.72-5.67 (overlapping signals, 2H, H-2 and H-4), 5.61 (dd, J = 8.4, 3.4
Hz, 1H, H-3), 4.74 (d, J = 5.9 Hz, 1H, H-1), 4.32 (dd, J = 12.7, 4.5 Hz, 1H, H-5a), 3.96-3.87
(overlapping signals, 2H, H-5b and OCHH), 3.54 (dt, J = 9.6, 6.6 Hz, 1H, OCHH), 1.64-1.55
(overlapping signals, 2H, OCH2CH2), 1.35-1.27 (overlapping signals, 2H, O(CH2)2CH2), 0.80
13
(t, J = 7.4 Hz, 3H, CH3); C NMR (126 MHz, CDCl3) δ 165.7, 165.6, 165.2 (each C=O),
133.3, 133.3, 133.2, 129.9, 129.8, 129.8, 129.4, 129.2, 128.4, 128.4, 128.3, 110.0 (each Ar-C
and CH), 77.2 (C-1), 70.4 (C-3), 70.0 (C-2), 69.5 (OCH2), 68.3 (C-4), 62.2 (C-5), 31.5
(OCH2CH2), 19.1 (O(CH2)2CH2), 13.7 (CH3); IR (ATR) cm-1: 1719, 1604, 1457, 1256, 1071,
1030, 712, 688; ES-HRMS calcd for C30H30O8Na 541.1838, found m/z 541.1849 [M+Na]+.
Butyl 2,3,4-tri-O-acetyl-β-L-fucopyranoside 5β Reaction
of
2,3,4-tri-O-acetyl-α-L-
fucopyranosyl bromide35 (1.44 g, 4.08 mmol), I2 (1.0 g, 4.08 mmol), DDQ (0.46 g, 2.04
mmol) and n-butanol (0.75 mL, 8.15 mmol) in dry CH2Cl2 (13 mL) as described for the
preparation of 1β, gave, after chromatography (cyclohexane-EtOAc 2:1), the title compound
1
as a colourless oil (0.63 g; 45 %); Rf 0.17 (cyclohexane-EtOAc 3:2); H NMR (500 MHz,
CDCl3) δ 5.23 (dd, J = 3.5, 1.1 Hz, 1H, H-4), 5.18 (dd, J = 10.5, 7.9 Hz, 1H. H-2), 5.02 (dd, J
= 10.5, 3.5 Hz, 1H, H-3), 4.42 (d, J = 7.9 Hz, 1H, H-1), 3.91 (dt, J = 9.6, 6.2 Hz, 1H, OCHH),
3.79 (qd, J = 6.4, 1.1 Hz, 1H, H-5), 3.46 (dt, J = 6.9, 4.1, 2.7 Hz, 1H, OCHH), 2.17 (s, 3H,
CO)CH3), 2.04 (s, 3H, C(O)CH3), 1.98 (s, 3H, C(O)CH3), 1.64-1.48 (overlapping signals, 2H,
OCH2CH2), 1.40-1.30 (overlapping signals, 2H, O(CH2)2CH2), 1.23 (d, J = 6.4 Hz, 3H, CH3),
13
0.90 (t, J = 7.4 Hz, 3H, CH2CH3); C NMR (126 MHz, CDCl3) δ 170.7, 170.3, 169.5 (each
18

ACCEPTED MANUSCRIPT
C=O), 101.2 (C-1), 71.4 (C-3), 70.4 (C-4), 69.8 (OCH2), 69.1 (C-2), 69.1 (C-5), 31.4
(OCH2CH2), 20.8, 20.7, 20.7 (each C(O)CH3), 19.0 (O(CH2)2CH2), 16.1 (CH3), 13.8
(CH2CH3); IR cm-1: 3707, 2966, 1744, 1367, 1215, 1174, 1033, 1017; ES-HRMS calcd for
C16H26O8Na 369.1525, found m/z 369.1522 [M+Na]+.
Butyl 2,3,4-tri-O-benzoyl-β-L-fucopyranoside 6β
Reaction of 2,3,4-tri-O-benzoyl-
β-L
-fucopyranosyl bromide36 (1.10 g, 2.04 mmol), I2 (0.71 g, 2.79 mmol), DDQ (0.32g, 1.39
mmol) and n-butanol (0.51 mL, 5.57 mmol) in dry CH2Cl2 (14 mL), as described for the
preparation of 1β, gave, after chromatography (cyclohexane-EtOAc 3:2), the title compound
(0.57 g, 57%) as a white solid: Rf 0.29 (2:3 EtOAc-cyclohexane); ꢁαꢂꢍꢌꢃ -180 (c 1.0, CHCl3);
1H NMR (500 MHz, CDCl3) δ 8.13-8.08 (overlapping signals, 2H, Ar-H), 7.98-7.94
(overlapping signals, 2H, Ar-H), 7.82-7.77 (overlapping signals, 2H, Ar-H), 7.63-7.58 (m,
1H, Ar-H), 7.53-7.45 (overlapping signals, 3H, Ar-H), 7.44-7.40 (m, 1H, Ar-H), 7.38 (t, J =
7.7 Hz, 2H, Ar-H), 7.25-7.21 (overlapping signals, 2H, Ar-H), 5.74 (dd, J = 10.5, 8.0 Hz, 1H,
H-2), 5.71 (d, J = 3.6 Hz, 1H, H-4), 5.55 (dd, J = 10.4, 3.5 Hz, 1H, H-3), 4.74 (d, J = 8.0 Hz,
1H, H-1), 4.07 (q, J = 6.4 Hz, 1H, H-5), 3.97 (dt, J = 9.8, 6.3 Hz, 1H, OCHH), 3.55 (dt, J =
9.8, 6.8 Hz, 1H, OCHH), 1.60-1.47 (overlapping signals, 2H, OCH2CH2), 1.36 (d, J = 6.4 Hz,
3H, CH3), 1.30-1.18 (overlapping signals, 2H, O(CH2)2CH2), 0.75 (t, J = 7.4 Hz, 3H,
O(CH2)3CH3); 13C NMR (126 MHz, CDCl3) δ 166.0, 165.7, 165.3 (each C=O), 133.4, 133.2,
133.0, 130.0, 129.8, 129.7, 129.3, 129.0, 128.5, 128.3, 128.2 (Ar-C and CH), 101.5 (C-1),
72.2 (C-3), 71.2 (C-2), 70.0 (OCH2), 69.9 (C-4), 69.7 (C-5), 31.4 (OCH2CH2), 18.9
(O(CH2)2CH2), 16.4 (CH3), 13.6 (CH2CH3); IR (ATR) cm-1: 1722, 1602, 1452, 1259, 1066,
1026, 705; ES-HRMS calcd for C31H32O8Na 555.1995, found m/z 555.1996 [M+Na]+.
19

ACCEPTED MANUSCRIPT
Butyl 2,3,4-tri-O-acetyl-1-D-thioxylopyranoside 7
2,3,4-Tri-O-acetyl-1-thio-D-
xylopyranose37 (0.3 g, 1.0 mmol) was dissolved in anhydrous CH2Cl2 (10 mL). To this,
DIPEA (0.38 mL, 2.16 mmol) and iodobutane (0.53 mL, 4.62 mmol) were added at room
temp. The mixture was stirred for 3 h and the solvent was removed under reduced pressure.
Chromatography of the residue (4:1 cyclohexane-EtOAc) gave the two anomers of 7 (α-
anomer: 0.05 g, 14%; β-anomer: 0.19 g, 53%) as pale yellow solids. Analytical data for 7α:
Rf 0.3 (cyclohexane-EtOAc 4:1); 1H NMR (500 MHz, CDCl3) δ 5.53 (d, J = 5.4 Hz, 1H, H-
1), 5.34 (t, J = 9.4 Hz, 1H, H-3), 4.98-4.87 (overlapping signals, 2H, H-2 and H-4), 4.03 (t, J
= 10.8 Hz, 1H, H-5a), 3.79 (dd, J = 11.3, 5.7 Hz, 1H, H-5b), 2.59-2.47 (overlapping signals,
2H, SCH2), 2.07 (s, 3H, C(O)CH3), 2.04 (s, 6H, 2 x C(O)CH3), 1.62-1.52 (overlapping
signals, 2H, SCH2CH2), 1.45-1.34 (overlapping signals, 2H, S(CH2)2CH2), 0.91 (t, J = 7.3
Hz, 3H, CH3); 13C NMR (126 MHz, CDCl3) δ 170.0 (2s), 169.7 (each C=O), 82.2 (C-1), 70.8
(C-2), 69.6 (C-3), 69.2 (C-4), 59.2 (C-5), 31.5 (SCH2CH2), 30.0 (SCH2), 21.9 (S(CH2)2CH2),
20.8, 20.7 (overlapping signals, each C(O)CH3), 13.6 (CH3); IR (ATR) cm-1: 2931, 1747,
1367, 1211, 1068, 1038; ESI-HRMS calcd for C15H28O7NS 366.1586, found m/z 366.1587
1
[M+NH4]+. Analytical data for 7β : Rf 0.24 (cyclohexane-EtOAc 4:1); H NMR (500
MHz, CDCl3) δ 5.18 (t, J = 8.5 Hz, 1H, H-3), 4.99-4.93 (overlapping signals, 2H, H-2 and H-
4), 4.51 (d, J = 8.7 Hz, 1H, H-1), 4.22 (dd, J = 11.6, 5.1 Hz, 1H, H-5a), 3.38 (dd, J = 11.6, 9.1
Hz, 1H, H-5b), 2.73-2.60 (overlapping signals, 2H, SCH2), 2.07 (s, 3H, C(O)CH3), 2.05 (s,
6H, 2 x C(O)CH3), 1.61-1.53 (overlapping signals, 2H, SCH2CH2), 1.44-1.36 (overlapping
13
signals, 2H, S(CH2)2CH2), 0.91 (t, J = 7.3 Hz, 3H, CH3); C NMR (126 MHz, CDCl3) δ
170.0, 169.8, 169.4 (each C=O), 83.8 (C-1), 72.3 (C-3), 69.8 (C-2), 68.7 (C-4), 65.6 (C-5),
31.6 (SCH2CH2), 29.7 (SCH2), 21.9 (S(CH2)2CH2), 20.7, 20.7, 20.7 (each C(O)CH3), 13.6
(CH3); IR (ATR) cm-1: 2957, 1748, 1366, 1207, 1063, 1051; ESI-HRMS calcd for
C15H28O7NS 366.1586, found m/z 366.1582 [M+NH4]+.
20

ACCEPTED MANUSCRIPT
Butyl 2,3,4-tri-O-benzoyl-1-D-thioxylopyranoside
8
2,3,4-Tri-O-benzoyl-1-thio-D-
xylopyranose13 (0.5 g, 1.05 mmol), was dissolved in anhydrous CH2Cl2 (10 mL). Then
DIPEA (0.36 mL, 2.09 mmol) and iodobutane (0.53 mL, 4.75 mmol) were added at room
temp and the mixture was stirred for 3 h. The solvent was removed under reduced pressure.
Chromatography of the residue (13:1 cyclohexane-EtOAc) gave the two anomers of 8 (0.21
g, 38%) and the β-anomer (0.24 g, 43%), each as a white solid. Analytical data for 8α: Rf 0.3
1
(cyclohexane-EtOAc, 12:1); ꢁαꢂꢌꢍꢃ +73 (c 1.0, CHCl3); H NMR (500 MHz, CDCl3) δ 8.03-
7.90 (overlapping signals, 6H, Ar-H), 7.54-7.49 (overlapping signals, 2H, Ar-H), 7.49-7.44
(m, 1H, Ar-H), 7.43-7.29 (overlapping signals, 6H, Ar-H), 5.99 (t, J = 9.2 Hz, 1H, H-3), 5.77
(d, J = 5.3 Hz, 1H, H-1), 5.43 (dd, J = 9.6, 5.3 Hz, 1H, H-2), 5.37 (td, J = 9.4, 5.5 Hz, 1H, H-
4), 4.28 (t, J = 10.7 Hz, 1H, H-5a), 4.10 (dd, J = 11.3, 5.4 Hz, 1H, H-5b), 2.65-2.53
(overlapping signals, 2H, SCH2), 1.63-1.53 (overlapping signals, 2H, SCH2CH2), 1.42-1.31
(overlapping signals, 2H, S(CH2)2CH2), 0.87 (t, J = 7.4 Hz, 3H, CH3); 13C NMR (126 MHz,
CDCl3) δ 165.6, 165.5, 165.5 (each C=O), 133.4, 133.4, 133.2, 130.0, 129.8, 129.7, 129.2,
129.1, 129.0, 128.4, 128.4, 128.3 (Ar-C and CH), 82.8 (C-1), 71.5 (C-2), 70.1 (C-3), 69.9 (C-
4), 59.7 (C-5), 31.6 (SCH2CH2), 30.2 (SCH2), 21.9 (S(CH2)2CH2), 13.6 (CH3); IR (ATR) cm-
1: 2958, 1720, 1452, 1251, 1093, 1068, 704, 687; ESI-HRMS calcd for C30H34O7SN
552.2056, found m/z 552.2047 [M+NH4]+. Analytical data for 8β Rf 0.21 (cyclohexane -
1
EtOAc 12:1); ꢁαꢂꢍꢌꢃ +35.1 (c 1.0, CHCl3); H NMR (500 MHz, CDCl3) δ 8.03-7.95
(overlapping signals, 6H, Ar-H), 7.56-7.47 (overlapping signals, 3H, Ar-H), 7.41-7.31
(overlapping signals, 6H, Ar-H), 5.77 (t, J = 7.2 Hz, 1H, H-3), 5.44 (t, J = 7.0 Hz, 1H, H-2),
5.31 (td, J = 7.3, 4.3 Hz, 1H, H-4), 4.96 (d, J = 7.1 Hz, 1H, H-1), 4.60 (dd, J = 11.9, 4.4 Hz,
1H, H-5a), 3.72 (dd, J = 12.0, 7.4 Hz, 1H, H-5b), 2.81-2.67 (overlapping signals, 2H, SCH2),
1.67-1.56 (overlapping signals, 2H, SCH2CH2), 1.46-1.35 (overlapping signals, 2H, ,
21

ACCEPTED MANUSCRIPT
13
S(CH2)2CH2), 0.90 (t, J = 7.4 Hz, 3H, CH3); C NMR (126 MHz, CDCl3) δ 165.5, 165.3,
165.2 (each C=O), 133.4, 133.3, 129.9, 129.9, 129.0, 128.4, 128.4, 128.3 (Ar-C and CH),
83.7 (C-1), 71.1 (C-3), 70.2 (C-2), 69.1 (C-4), 64.1 (C-5), 31.7 (SCH2CH2), 30.4 (SCH2),
21.9 (S(CH2)2CH2), 13.6 (CH3); IR (ATR) cm-1: 1717, 1453, 1246, 1094, 1067, 1028, 704;
ESI-HRMS calcd for C30H30O7SNa 557.1610, found m/z 557.1611 [M+Na]+.
Butyl 2,3,4-tri-O-benzoyl-1-thio-α-L-arabinopyranoside 9α
2,3,4-Tri-O-benzoyl-1-
thio-α- -arabinopyranose (0.50 g, 1.05 mmol) was dissolved in anhydrous CH2Cl2 (10 mL).
L
DIPEA (0.36 mL, 2.09 mmol) and iodobutane (0.53 mL, 4.75 mmol) were added at room
temp and the mixture was stirred for 15 h. The solvent was then removed and
chromatography of the residue (12:1 cyclohexane-EtOAc) gave the title compound (0.47 g,
83%), as a white solid: Rf 0.43 (cyclohexane-EtOAc, 5:1); ꢁαꢂꢍꢌꢃ +132.2 (c 1.0, CHCl3); 1H-
NMR (500 MHz, CDCl3) δ 8.06-7.99 (overlapping signals, 4H, Ar-H), 8.00-7.92
(overlapping signals, 2H, Ar-H), 7.60-7.52 (overlapping signals, 2H, Ar-H), 7.52-7.47 (m,
1H, Ar-H), 7.47-7.38 (overlapping signals, 4H, Ar-H), 7.39-7.31 (overlapping signals, 2H,
Ar-H), 5.79 (t, J = 7.9 Hz, 1H, H-2), 5.72 (apparent q, J = 3.4 Hz, 1H, H-4), 5.64 (dd, J = 8.2,
3.4 Hz, 1H, H-3), 4.88 (d, J = 7.7 Hz, 1H, H-1), 4.43 (dd, J = 12.7, 4.3 Hz, 1H, H-5a), 3.93
(dd, J = 12.8, 2.2 Hz, 1H, H-5b), 2.81 (ddd, J = 12.8, 8.3, 6.3 Hz, 1H, SCHH), 2.74 (dt, J =
12.6, 7.5 Hz, 1H, SCHH), 1.69-1.57 (overlapping signals, J = 6.7 Hz, 2H, SCH2CH2), 1.41
(h, J = 7.3 Hz, 2H, S(CH2)2CH2), 0.90 (t, J = 7.4 Hz, 3H, CH3); 13C NMR (126 MHz, CDCl3)
δ 165.6, 165.5, 165.3 (each C=O), 133.4, 133.4, 133.3, 129.9, 129.9, 129.8, 129.4, 129.0,
128.5, 128.4, 128.4 (Ar-C and CH), 83.92 (C-1), 71.2 (C-3), 69.3 (C-2), 68.7 (C-4), 31.9
(SCH2), 30.3 (SCH2CH2), 22.0 (S(CH2)2CH2), 13.6 (CH3); IR (ATR) cm-1: 2960, 1727, 1451,
1251, 1082, 1067, 1026, 704; ES-HRMS calcd for C26H22O7SNa 557.1610, found m/z
557.1605 [M+Na]+.
22

ACCEPTED MANUSCRIPT
Butyl 2,3,4-Tri-O-benzoyl-1-thio-β-L-fucopyranoside 10β
2,3,4-Tri-O-benzoyl-1-
thio-β- -fucopyranoside (0.5 g, 1.02 mmol) was dissolved in anhydrous CH2Cl2 (10 mL).
L
DIPEA (0.36 mL, 2.09 mmol) and iodobutane (0.53 mL, 4.75 mmol) were then added and the
mixture was stirred for 6 h at room temp. The solvent was removed and then
chromatography of the residue (cyclohexane-EtOAc 10:1) gave the title compound (0.452 g,
1
81%), as a white solid; Rf 0.34 (cyclohexane-EtOAc 10:1); ꢁαꢂꢍꢌꢃ -191.1 (c 1.0, CHCl3); H
NMR (500 MHz, CDCl3) δ 8.12-8.07 (overlapping signals, 2H, Ar-H), 8.00-7.93
(overlapping signals, 2H, Ar-H), 7.80-7.76 (overlapping signals, 2H, Ar-H), 7.64-7.57 (m,
1H, Ar-H), 7.52-7.46 (overlapping signals, 3H, Ar-H), 7.44-7.34 (overlapping signals, 3H,
Ar-H), 7.26-7.20 (overlapping signals, 2H, Ar-H), 5.82 (t, J = 9.9 Hz, 1H, H-2), 5.76 (d, J =
3.5 Hz, 1H, H-4), 5.59 (dd, J = 9.9, 3.4 Hz, 1H, H-3), 4.77 (d, J = 9.8 Hz, 1H, H-1), 4.11 (q, J
= 6.4 Hz, 1H, H-5), 2.87 (ddd, J = 12.3, 8.7, 6.2 Hz, 1H, SCHH), 2.78 (ddd, J = 12.3, 8.7, 6.8
Hz, 1H, SCHH), 1.71-1.58 (overlapping signals, 2H, SCH2CH2), 1.49-1.37 (overlapping
signals, 2H, S(CH2)2CH2), 1.35 (d, J = 6.4 Hz, 3H, CH3), 0.91 (t, J = 7.3 Hz, 3H,
S(CH2)3CH3); 13C NMR (126 MHz, CDCl3) δ 165.9, 165.6, 165.4 (each C=O), 133.4, 133.2,
133.2, 129.9, 129.7, 129.7, 129.4, 129.3, 128.5, 128.3, 128.2 (Ar-C and CH), 83.7 (C-1), 73.8
(C-5), 73.2 (C-3), 71.3 (C-4), 68.1 (C-2), 31.8 (SCH2CH2), 29.5 (SCH2), 22.0 (S(CH2)2CH2),
16.7 (CH3), 13.6 (S(CH2)3CH3); IR (ATR) cm-1: 2960, 1721, 1451,1256, 1094, 1067, 1026,
703; ES-HRMS calcd for C31H32O7SNa 571.1766, found m/z 571.1744 [M+Na]+.
Isopropyl 2,3,4-tri-O-acetyl-β-D-xylopyranoside 12β
Glycosylation reaction with
2,3,4-tri-O-acetyl-α-D-xylopyranosyl bromide (0.92 g, 3.12 mmol), I2 (0.8 g, 3.13 mmol),
DDQ (0.36 g, 1.57 mmol) and isopropanol (0.48 mL, 6.26 mmol) in anhydrous CH2Cl2
(15.65 mL) as described above, gave after chromatography (cyclohexane-EtOAc 2:1), the
23

ACCEPTED MANUSCRIPT
title compound (0.27 g, 27%) as a white solid; Rf 0.32 (cyclohexane-EtOAc 3:2); ꢁαꢂꢍꢌꢃ -54.5
1
(c 1.0, CHCl3); H NMR (500 MHz, CDCl3) δ 5.17 (t, J = 8.9 Hz, 1H, H-3), 4.95 (td, J = 9.0,
5.3 Hz, 1H, H-4), 4.88 (dd, J = 9.0, 7.0 Hz, 1H, H-2), 4.52 (d, J = 7.1 Hz, 1H, H-1), 4.11 (dd,
J = 11.7, 5.3 Hz, 1H, H-5a), 3.90 (hept, J = 6.0 Hz, 1H, CH(CH3)2), 3.33 (dd, J = 11.7, 9.2
Hz, 1H, H-5b), 2.05 (s, 3H, C(O)CH3), 2.04 (s, 3H, C(O)CH3), 2.03 (s, 3H, C(O)CH3), 1.22
13
(d, J = 6.2 Hz, 3H, CH3), 1.13 (d, J = 6.2 Hz, 3H, CH3); C NMR (126 MHz, CDCl3) δ
170.2, 169.8, 169.4 (each C=O), 99.5 (C-1), 72.2 (CH(CH3)2), 71.8 (C-3), 71.2 (C-2), 69.0
(C-4), 62.1 (C-5), 23.3, 21.8 (each CH3), 20.7 (3s) (each C(O)CH3); IR (ATR) cm-1: 2983,
1749, 1366, 1217, 1072, 1060; ESI-HRMS calcd for C14H22O8Na 341.1212, found m/z
341.1212 [M+Na]+.
Isopropyl 2,3,4-tri-O-benzoyl-β-D-xylopyranoside 13β Glycosylation using 2,3,4-tetra-O-
benzoyl-α-D-xylopyranosyl bromide (1.19 g, 2.26 mmol), I2 (0.58 g, 2.26 mmol), DDQ (0.26
g, 1.13 mmol) and isopropanol (0.35 mL, 4.53 mmol) as described for the preparation of 1β,
gave, after chromatography (cyclohexane-EtOAc 6:1), the title compound (0.47 g, 41%) as a
1
white solid. Rf 0.28 (cyclohexane-EtOAc 6:1); ꢁαꢂꢍꢌꢃ -32.6 (c 1.0, CHCl3); H NMR (500
MHz, CDCl3) δ 8.02-7.96 (overlapping signals, 6H, Ar-H), 7.56-7.47 (overlapping signals,
3H, Ar-H), 7.39-7.33 (overlapping signals, 6H, Ar-H), 5.76 (t, J = 7.3 Hz, 1H, H-3), 5.35-
5.26 (overlapping signals, 2H, H-2 and H-4), 4.90 (d, J = 5.5 Hz, 1H, H-1), 4.44 (dd, J =
12.1, 4.3 Hz, 1H, H-5a), 4.00 (hept, J = 6.2 Hz, 1H, CH(CH3)2), 3.69 (dd, J = 12.1, 7.2 Hz,
13
1H, H-5b), 1.27 (d, J = 6.2 Hz, 3H, CH3), 1.12 (d, J = 6.1 Hz, 3H, CH3); C NMR (126
MHz, CDCl3) δ 165.5, 165.4, 165.1 (each C=O), 133.3, 133.2, 133.1, 129.9, 129.8, 129.8,
129.5, 129.3, 129.2, 128.4, 128.3 (Ar-C and CH), 98.6 (C-1), 71.7 (CH(CH3)2), 70.7 (C-2),
70.75 (C-3), 69.3 (C-4), 61.3 (C-5), 23.3 (CH3), 21.7 (CH3); IR (ATR) cm-1: 2975, 1720,
24

ACCEPTED MANUSCRIPT
1602, 1452, 1249, 1089, 1068, 1026, 705, 686; ESI-HRMS calcd for C29H28O8Na 527.1682,
found m/z 527.1685 [M+Na]+.
Anomerisation Reactions including Kinetics Experiments. Typically, the reactant (~30
mg) was dissolved in anhydrous CH2Cl2 to generate a 0.2 M solution which was then placed
under nitrogen or argon. SnCl4 (1.0 M in CH2Cl2) or TiCl4 (1.0 M in CH2Cl2) was added at
room temp, and the mixture was cooled to 4 °C or -30 °C or left to stir at room temperature
(~20 °C). The mixture was left for 24 h before diluting with EtOAc and washing with 1.0 M
KHSO4 (for SnCl4) or 1.0 M NH4Cl (for TiCl4). The aqueous layer was extracted with EtOAc
and the combined organic layers were washed with satd NaHCO3 and brine, dried over
Na2SO4 and then the solvent was removed under reduced pressure. For kinetics experiments,
the reactant (0.068 mmol) was dried prior to the reaction, before dissolving in freshly distilled
CDCl3 (0.75 mL) and then placed in a 5 mm NMR tube. SnCl4 (0.1 mL of an 0.34 M solution
in CDCl3) was then added and the concentration of the anomers was measured by 1H-NMR
spectroscopy at 25°C , usually over several days until equilibrium was attained. The reaction
mixture was then diluted with EtOAc, washed with KHSO4, satd. NaHCO3, brine and dried
1
over Na2SO4. This product was analysed by H-NMR spectroscopy to obtain the ratio of
products. The solvent was removed under reduced pressure and the resulting residue was
subjected to column chromatography providing a sample of the axial anomer for analytical
purposes, and also for determination of the isolated yield. The CDCl3 used in the kinetic
experiments was pre-distilled over phosphorus pentoxide and analysed for water content
before use; usually the presence of H2O can be detected by 1H-NMR due to it having a signal
at ~ δ 1.60 ppm. NMR tubes were dried in an oven before use. A fresh solution of SnCl4
was prepared for each sample. The average integration of 2-3 signals in the NMR spectrums
was used to determine the concentration of the α- and β-anomers during monitoring. The
25

ACCEPTED MANUSCRIPT
kinetics experiments were carried out in triplicate for each reactant and average kf+kr values
and average ratios are reported in the manuscript.
Butyl 2,3,4-tri-O-acetyl-α-D-xylopyranoside 1α Rf 0.38 (cyclohexane- EtOAc 4:1); ꢁαꢂꢌꢍꢃ
-51.6 (c 1.0, CHCl3); 1H NMR (500 MHz, CDCl3) δ 5.48 (t, J = 9.8 Hz, 1H, H-3), 4.99 (d, J =
3.7 Hz, 1H, H-1), 4.99-4.91 (m, 1H, H-4), 4.79 (dd, J = 10.2, 3.6 Hz, 1H, H-2), 3.77 (dd, J =
10.9, 5.9 Hz, 1H, H-5a), 3.69 (dt, J = 9.8, 6.5 Hz, 1H, OCHH), 3.62 (t, J = 10.8 Hz, 1H, H-
5b), 3.39 (dt, J = 9.8, 6.5 Hz, 1H, OCHH), 2.17 (s, 3H, C(O)CH3), 2.06 (s, 3H, C(O)CH3),
2.03 (s, 3H, C(O)CH3), 1.62-1.54 (overlapping signals, 2H, OCH2CH2), 1.44-1.34
(overlapping signals, 2H, O(CH2)CH2), 0.93 (t, J = 7.4 Hz, 3H, CH3);13C NMR (126 MHz,
CDCl3) δ 170.3, 170.1, 170.0 (each C=O), 95.6 (C-1), 71.2(C-2), 69.7 (C-3), 69.5 (C-4), 68.2
(C-5), 58.2 (OCH2), 30.9 (OCH2CH2), 20.8, 20.7, 20.7 (each C(O)CH3), 19.2 (O(CH2)2CH2),
13.8 (CH3); IR (ATR) cm-1: 2922, 1741, 1369, 1223, 1078, 1058. 1030; ESI-HRMS calcd for
C15H24O8Na 355.1369, found m/z 355.1368 [M+Na]+.
Butyl 2,3,4-tri-O-benzoyl-β-D-xylopyranoside 2α Rf 0.27 (cyclohexane-EtOAc 7:1); ꢁαꢂꢌꢍꢃ
+71.13 (c 1.0, CHCl3); 1H NMR (500 MHz, CDCl3) δ 8.02-7.95 (overlapping signals, 4H, Ar-
H), 7.95-7.89 (overlapping signals, 2H, Ar-H), 7.55-7.49 (overlapping signals, 2H, Ar-H),
7.47-7.42 (m, 1H, Ar-H), 7.42-7.35 (overlapping signals, 4H, Ar-H), 7.34-7.28 (overlapping
signals, 2H, Ar-H), 6.16 (t, J = 9.8 Hz, 1H, H-3), 5.39 (td, J = 10.1, 5.8 Hz, 1H, H-4), 5.28-
5.23 (overlapping signals, 2H, H-1 and H-2), 4.07 (dd, J = 10.8, 5.9 Hz, 1H, H-5a), 3.87 (t, J
= 10.8 Hz, 1H, H-5b), 3.78 (dt, J = 9.9, 6.4 Hz, 1H, OCHH), 3.45 (dt, J = 9.8, 6.5 Hz, 1H,
OCHH), 1.65-1.51 (overlapping signals, 2H, OCH2CH2), 1.41-1.30 (overlapping signals, 2H,
O(CH2)2CH2), 0.84 (t, J = 7.3 Hz, 3H, CH3); 13C NMR (126 MHz, CDCl3) δ 165.85, 165.80,
165.63 (each C=O), 133.33, 133.28, 133.09, 129.85, 129.82, 129.68, 129.39, 129.16, 129.13,
128.41, 128.29, 128.28 (Ar-C and CH), 96.07 (C-1), 71.98 (C-2), 70.34 (C-4), 70.07 (C-3),
26

ACCEPTED MANUSCRIPT
68.46 (OCH2), 58.59 (C-5), 31.38 (OCH2CH2), 19.19 (O(CH2)2CH2), 13.68 (CH3); IR (ATR)
cm-1: 2951, 1719, 1252, 1094, 1043, 705, 687; ESI-HRMS calcd for C30H30O8Na 548.1838,
found m/z 548.1833 [M+Na]+.
Butyl 2,3,4-tri-O-acetyl-β-L-arabinopyranoside 3α
Rf
0.48
(2:3
EtOAc-
1
cyclohexane); ꢁαꢂꢍꢌꢃ +150.3 (c 1.0, CHCl3); H NMR (500 MHz, CDCl3) δ 5.37-5.33
(overlapping signals, 2H, H-3 and H-4), 5.15 (dd, J = 9.9, 3.5 Hz, 1H, H-2), 5.07 (d, J = 3.6
Hz, 1H, H-1), 3.96 (dd, J = 13.2, 1.2 Hz, 1H, H5a), 3.72-3.64 (overlapping signals, 2H, H-5b
and OCHH), 3.40 (dt, J = 9.7, 6.5 Hz, 1H, OCHH), 2.14 (s, 3H, C(O)CH3), 2.07 (s, 3H,
C(O)CH3), 2.01 (s, 3H, C(O)CH3), 1.61-1.53 (overlapping signals, 2H, OCH2CH2), 1.44-1.34
13
(overlapping signals, 2H, O(CH2)CH2), 0.93 (t, J = 7.4 Hz, 3H, CH3); C NMR (126 MHz,
CDCl3) δ 170.4, 170.4, 170.1 (each C=O), 96.3 (C-1), 69.2 (C-3), 68.5 (C-5), 68.2 (C-2), 67.3
(C-4), 60.3 (OCH2), 31.4 (OCH2CH2), 20.9, 20.8, 20.7 (each C(O)CH3), 19.2 (O(CH2)CH2),
13.7 (CH3); IR (ATR) cm-1: 2961, 1740, 1371, 1217, 1062; ESI-HRMS calcd for C15H28O8N
350.1815, found m/z 350.1820 [M+NH4]+.
Butyl 2,3,4-tri-O-benzoyl-β-L-arabinopyranoside 4α
Rf 0.31 (cyclohexane-EtOAc
6:1); 1H NMR (500 MHz, CDCl3) δ 8.12-8.08 (overlapping signals, 2H, Ar-H), 8.00-7.97 (m,
1H, Ar-H), 7.89-7.82 (overlapping signals, 2H, Ar-H), 7.62-7.57 (m, 1H, Ar-H), 7.54-7.42
(overlapping signals, 4H, Ar-H), 7.41-7.36 (overlapping signals, 2H, Ar-H), 7.29-7.25
(overlapping signals, 3H, Ar-H), 5.94 (dd, J = 10.7, 3.6 Hz, 1H, H-3), 5.75 (dt, J = 3.5, 1.6
Hz, 1H, H-4), 5.71 (dd, J = 10.7, 3.6 Hz, 1H, H-2), 5.32 (d, J = 3.5 Hz, 1H, H-1), 4.21 (dd, J
= 13.2, 1.4 Hz, 1H, H-5a), 3.95 (dd, J = 13.1, 2.0 Hz, 1H, H-5b), 3.79 (dt, J = 9.8, 6.4 Hz,
1H, OCHH), 3.47 (dt, J = 9.8, 6.5 Hz, 1H, OCHH), 1.63-1.56 (overlapping signals, 2H,
OCH2CH2), 1.44-1.34 (overlapping signals, 2H, O(CH2)2CH2), 0.86 (t, J = 7.4 Hz, 3H, CH3);
13C NMR (126 MHz, CDCl3) δ 166.1, 165.8, 165.6 (each C=O), 133.3, 133.3, 133.1, 129.8,
129.8, 129.7, 129.3, 129.3, 128.5, 128.5, 128.4, 128.3, 128.3 (Ar-C and CH), 96.8 (C-1), 70.3
27

ACCEPTED MANUSCRIPT
(C-4), 69.5 (C-2), 68.4 (OCH2), 68.1 (C-3), 60.5 (C-5), 31.4 (OCH2CH2), 19.2
(O(CH2)2CH2), 13.7 (CH3); IR (ATR) cm-1: 2959, 1719, 1451, 1248, 1092, 1068, 1026, 705,
686; ESI-HRMS calcd for C30H34O8N 536.2284, found m/z 536.2285 [M+NH4]+.
Butyl 2,3,4-tri-O-acetyl-α-
-fucopyranoside 5α Rf 0.41 (cyclohexane-EtOAc 2:1); ꢁαꢂꢌꢍꢃ
L
1
-134.3 (c 1.0, CHCl3); H NMR (500 MHz, CDCl3) δ 5.36 (dd, J = 10.7, 3.4 Hz, 1H, H-3),
5.30 (d, J = 3.3 Hz, 1H, H-4), 5.10 (dd, J = 10.8, 3.8 Hz, 1H, H-2), 5.05 (d, J = 3.6 Hz, 1H,
H-1), 4.16 (q, J = 6.5 Hz, 1H, H-5), 3.68 (dt, J = 9.8, 6.5 Hz, 1H, OCHH), 3.41 (dt, J = 9.8,
6.5 Hz, 1H, OCHH), 2.16 (s, 3H, C(O)CH3), 2.07 (s, 3H, C(O)CH3), 1.99 (s, 3H, C(O)CH3),
1.61-1.52 (overlapping signals, 2H, OCH2CH2), 1.43-1.33 (overlapping signals, 2H,
13
O(CH2)2CH2), 1.14 (d, J = 6.6 Hz, 3H, CH3), 0.93 (t, J = 7.4 Hz, 3H, CH2CH3). C NMR
(126 MHz, CDCl3) δ 170.6, 170.5, 170.1 (each C=O), 96.0 (C-1), 71.2 (C-4), 68.4 (C-2),
68.2, 68.1 (overlapping signals, C-3 and OCH2), 64.2 (C-5), 31.4 (OCH2CH2), 20.8, 20.7,
20.7 (each C(O)CH3), 19.2 (O(CH2)2CH2), 15.9 (CH3), 13.7 (CH2CH3); IR (ATR) cm-1: 2917,
1743, 1371, 1220, 1048; ESI-HRMS calcd for C16H26O8Na 369.1525, found m/z 369.1522
[M+Na]+.
1
Butyl 2,3,4-tri-O-benzoyl-α-
L
-fucopyranoside 6α Rf 0.41 (cyclohexane-EtOAc 4:1); H
NMR (500 MHz, CDCl3) δ 8.13-8.08 (overlapping signals, 2H, Ar-H), 8.01-7.96
(overlapping signals, 2H, Ar-H), 7.82-7.77 (overlapping signals, 2H, Ar-H), 7.65-7.59 (m,
1H, Ar-H), 7.50 (overlapping signals, 3H, Ar-H), 7.45-7.40 (m, 1H, Ar-H), 7.40-7.35
(overlapping signals, 2H, Ar-H), 7.26-7.21 (overlapping signals, 2H, Ar-H), 5.96 (dd, J =
10.7, 3.5 Hz, 1H, H-3), 5.76 (dd, J = 3.5, 1.3 Hz, 1H, H-4), 5.64 (dd, J = 10.7, 3.7 Hz, 1H, H-
2), 5.32 (d, J = 3.7 Hz, 1H, H-1), 4.43 (qd, J = 6.5, 1.2 Hz, 1H, H-5), 3.78 (dt, J = 9.8, 6.4 Hz,
1H, OCHH), 3.48 (dt, J = 9.9, 6.5 Hz, 1H, OCHH), 1.62-1.56 (overlapping signals, 2H,
OCH2CH2), 1.44-1.33 (overlapping signals, 2H, O(CH2)2CH2), 1.28 (d, J = 6.6 Hz, 3H, CH3),
13
0.86 (t, J = 7.4 Hz, 3H, CH2CH3); C NMR (126 MHz, CDCl3) δ 166.1, 166.0, 165.7 (each
28