Photooxidation of thiosaccharides mediated by sensitizers in aerobic and environmentally friendly conditions

Article abstract of DOI:10.1039/d0ra09534f

A series of β-d-glucopyranosyl derivates have been synthesized and evaluated in photooxidation reactions promoted by visible light and mediated by organic dyes under aerobic conditions. Among the different photocatalysts employed, tetra-O-acetyl riboflavin afforded chemoselectively the respective sulfoxides, without over-oxidation to sulfones, in good to excellent yields and short reaction times. This new methodology for the preparation of synthetically useful glycosyl sulfoxides constitutes a catalytic, efficient, economical, and environmentally friendly oxidation process not reported so far for carbohydrates.

Full text of DOI:10.1039/d0ra09534f

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Photooxidation of thiosaccharides mediated by
sensitizers in aerobic and environmentally friendly
conditions†
Cite this: RSC Adv., 2021, 11, 9262
ab
cd
Miqueas G. Traverssi,ab Alicia B. Penenory,
Oscar Varela
˜´˜
ab
*
and Juan P. Colomer
A series of b-D-glucopyranosyl derivates have been synthesized and evaluated in photooxidation reactions
promoted by visible light and mediated by organic dyes under aerobic conditions. Among the different
photocatalysts employed, tetra-O-acetyl riboflavin afforded chemoselectively the respective sulfoxides,
without over-oxidation to sulfones, in good to excellent yields and short reaction times. This new
methodology for the preparation of synthetically useful glycosyl sulfoxides constitutes a catalytic,
efficient, economical, and environmentally friendly oxidation process not reported so far for carbohydrates.
Received 9th November 2020
Accepted 23rd February 2021
DOI: 10.1039/d0ra09534f
rsc.li/rsc-advances
specic glycosidases, showing different reactivity towards
enzymatic hydrolysis according to the S-conguration.18,20
Introduction
An important disadvantage of the methodologies described
for the oxidation of thiomonosaccharides employing conven-
tional oxidation agents, is the extremely low reaction tempera-
tures required to obtain the respective sulfoxides, without over-
oxidation to sulfone.6,21–23 Also, it is important to highlight that
these conditions are difficult to achieve and control.
Several reagents employed in the sulde oxidations are toxic,
generate by-products difficult to separate from the desired
product, and/or contain heavy metals that produce hazardous
goods. Furthermore, some of them are very efficient but also
very expensive and must be employed stoichiometrically.24 In
regard to some peroxy acids, certain limitations arise due to the
instability of the pure compounds. This is the case of m-chlor-
operbenzoic acid, which is rarely available with a purity higher
than 77%.25 Furthermore, the use of these compounds should
be avoided in production processes since they offer a low atom
economy. For all the reasons described above, the development
of an energy-saving, catalytic, atom-economical, environmen-
tally friendly, and highly selective oxidation process from thio-
ethers to sulfoxides is required.
Among the different oxidants, molecular oxygen is a awless
reagent since it is “practically unlimited” and “free”, as is light.
Photosensitized suldes oxidation occur according to two main
mechanisms (type I and type II).26,27 In type I mechanism, an
electron transfer between the sulde and the excited sensitizer
takes place, giving rise to sulde radical cation (RSR0c+) that
could follow different pathways:28 One of them affords the
respective sulfoxide and another one, is the fragmentation to
yield a thiyl radical cSR0 and alkyl cation R+ which evolves to
different products. However, the C–S bond cleavage is less
common for alkyl suldes than for aromatic suldes, and the
Sulfoxides play important roles as organic synthetic interme-
diates1 and biologically active compounds employed in the
pharmaceutical industry.2 Therefore, the development of new
chemoselective oxidation methodologies of suldes to sulfox-
ides, avoiding the formation of sulfones, has been increased.3–5
One of the most powerful glycosylation methods discovered
by Kahne and coworkers employs anomeric glycosyl sulfoxides
as glycoside donors.6 Since then, several reports describing the
study and synthesis of a wide range of glycosides7–12 and
oligosaccharides13,14 using this methodology have been re-
ported. Moreover, glycosyl sulfoxides have demonstrated
several biological applications such as the proliferation inhi-
bition of selected tumor cell lines,15 oral antithrombotic
activity,16 and the capability of binding to proteins.17 Addition-
ally, in previous works, our research group has synthesized
sulfoxide derivates of thiodisaccharides and established the
conguration at the sulfur stereocenter by a procedure devel-
oped by us employing high resolution 1D and 2D NMR tech-
niques.18,19 Furthermore, some of these diastereomeric
thiodisaccharides S-oxides (with different congurations at the
sulfur stereocenter) have demonstrated to inhibit the activity of
a
´
´
´
Departamento de Quımica Organica, Universidad Nacional de Cordoba, Facultad
´
´
Ciencias Quımicas, Ciudad Universitaria, Edicio de Ciencias II, Cordoba,
Argentina. E-mail: juanpablo@fcq.unc.edu.ar
bInstituto de Investigaciones en Fisico-Quımica de Cordoba (INFIQC), Consejo
´
´
´
´
Nacional de Investigaciones Cientıcas y Tecnicas (CONICET), UNC, Argentina
c
´
´
Departamento de Quımica Organica, Universidad de Buenos Aires, Facultad Ciencias
Exactas y Naturales, Ciudad Universitaria, Pab. 2, C1428EHA, Buenos Aires, Argentina
d
´
Centro de Investigacion en Hidratos de Carbono (CIHIDECAR), Consejo Nacional de
´
´
Investigaciones Cientıcas y Tecnicas (CONICET), UBA, Argentina
† Electronic supplementary information (ESI) available. See DOI:
10.1039/d0ra09534f
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Thus, penta-O-acetyl-D-glucopyranose 1 was stereoselectively
transformed into the b-thioaldose 2.38 Subsequently, 2 was
treated with dimethyl sulfate as methylating agent to afford the
thioglucoside 3a in 96% isolated yield aer simple extractions
from the reaction mixture. Other thiomonosaccharides were
also synthesized performing the reaction between 2 as glycosyl
acceptor and several alkyl/allyl bromides in acetonitrile and in
the presence of triethylamine. As shown in Scheme 1, all the
obtained products 3a–d maintain the b conguration of the
glycosyl acceptor precursor and the isolated yields range from
good to excellent (72–99%). The b conguration at the anomeric
centers of the alkyl/allyl thioglucose derivates was established
Scheme 1 Synthesis of thiomonosaccharides 3a–e.
according to the large coupling constant value (J1,2 z 9–10 Hz),
1
nature of cleavage products depends on the stabilization of the determined from the H NMR spectra.
cation intermediate.29,30
With the objective of determining the scope of the reaction
On the other hand, in a type II mechanism, an energy
transfer process occurs to generate singlet oxygen (1O2) that is
studied, an aryl thioglycoside was also synthesized employing
the procedure described in bibliography.39 The phenyl thio-
the responsible for the oxidation of the sulde into a perox- saccharide 3e, having the b-conguration at the anomeric
ysulfoxide intermediate. This intermediate reacts with another center, was obtained aer column chromatography purication
molecule of sulde to afford the respective sulfoxide.31
in 71% isolated yield (Scheme 1).
Several photooxidation methodologies of thioethers to sulf-
With the thiomonosaccharides in hand, we proceeded to
oxides are described in the bibliography.26,32–37 Despite the perform the photochemical oxidation studies employing
important role of glycosyl sulfoxides in glycosylation reactions
and the potential biological applications mentioned above, we
were not able to nd any study involving the photochemical
diverse photocatalysts under aerobic conditions. To optimize
the reaction settings, different variables as photocatalysts,
solvents, atmospheres, and time were evaluated using the thi-
oxidation of glycosyl suldes. Therefore, as continuation of our omonosaccharide 3a as a model substrate.
research on the oxidation of thioglycosides, we report here the
Several organic dyes are remarkably effective photosensi-
photosensitized oxidation of thiosaccharides under aerobic tizers under visible light, since they possess triplet states of
conditions. As catalytic amounts of organic dyes, oxygen, and proper energies for sensitization of oxygen.40,41 This photosen-
light are employed, instead of the stoichiometric amounts of sitization is capable to generate singlet oxygen which is one of
usually toxic oxidants, generally used for the oxidation of thio-
saccharides, this is considered to be a catalytic, efficient,
economical, and environmentally friendly method no reported
so far for carbohydrates.
the species capable of oxidizing suldes to sulfoxides. The
structures of some of these organic dyes are shown in Chart 1.
Aer each reaction, conversion was determined by 1H NMR
using the integrals of the 5-H signal of the thiosaccharides
(sulde and sulfoxide). The ratio of the diastereomeric sulfox-
ides obtained was calculated from specic signals of the
respective products.
Results and discussion
As starting conditions, the organic dyes were used as pho-
tocatalyst (1 mol%) in an oxygen atmosphere, in aprotic or
To study the photosensitized oxidation methodology, the thio-
saccharides 3a–e were synthesized and used as substrates.
Chart 1 Structures of some organic dyes that are effective photosensitizers capable to generate singlet oxygen under visible light.
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Table 2 Solvent screening for the photooxidation reaction of sulfide
3a to sulfoxide 4a
protic polar solvents (acetonitrile and isopropanol, respec-
tively), previously saturated with O2. The LED selection to irra-
diate the organic dyes was performed considering the
maximum absorption wavelengths of each sensitizer. When
uorescein was employed, the reaction mixtures were irradiated
under blue LED light (467 nm) for 48 h, but the substrate 3a
remains unalterable (Table 1, entries 1 and 2).
Subsequently, the reactions were repeated in the presence of
NaHCO3 to generate the basic form of the photocatalyst, since
the production of singlet oxygen by some dye photosensitiza-
tion was found to be very sensitive to pH changes.42 Neverthe-
less, the thiosaccharide 3a remained also unmodied (Table 1,
entries 3 and 4). We have selected this base as is nontoxic and
does not affect the substrate (otherwise O-deacetylation may
take place).
Entrya
Dye (mol%)
Solvent
Yield 4ab (%)
1
2
3
4
5
R6G (1)
R6G (1)
R6G (1)
R6G (1)
R6G (1)
MeCN
84
25
11
30
81
i-PrOH
MeOH
Me2CO
MeCN : MeOH
(9 : 1)
6
7
8
R6G (1)
R6G (1)
R6G (1)
CH2Cl2
PhMe
PEG
25
N.R.
N.R.
a
Reaction conditions: 3a (0.05 M), solvent (2 mL), 45 ꢁC, irradiated with
green LED (522 nm), oxygen atmosphere, 48 h. Determined by 1H
b
NMR. N.R. ¼ no reaction.
Aerward, the experiments carried out with Eosin Y (EY),
Rose Bengal (RB) or rhodamine 6G (R6G) gave the desired dia-
stereomeric sulfoxides 4a in varied yields (Table 1, entries 5–10).
The best result was obtained employing rhodamine 6G as
photocatalyst, which led to the diastereomeric sulfoxides 4a in
84% yield.
Once selected the best photocatalyst, a solvent screening was
evaluated to determine the more efficient medium to perform
the photooxidation reaction, as depicted in Table 2.
The photooxidation reaction works better in polar solvents
as MeCN and in a mixture MeCN : MeOH (9 : 1) (entries 1 and 5,
Table 2). Despite the particularly good conversions and high
chemoselectivities obtained towards the sulfoxides, we were
unsatised with the long reaction times required (48 h), without
complete consumption of the substrate, probably due to the
photocatalyst bleaching under such long periods of irradiation.
As efficient photooxidations of suldes to sulfoxides, under
visible light,26,34,35 mediated by riboavin derivates are
reported,37,43 we decided to evaluate the photooxidation reac-
tions employing tetra-O-acetyl riboavin (RFTA) as photo-
catalyst. First, riboavin (RF) was peracetylated employing
a protocol described in the bibliography.44 Then, the photooxi-
dation reactions were performed under various conditions, as
shown in Table 3. When MeCN, MeOH, EtOH or H2O were
employed as solvents, the degree of conversion was low (entries
1–4). Surprisingly, in MeCN : H2O (85 : 15) an excellent yield
(99%) and chemoselectivity were achieved in considerably lower
reaction times (entry 5). This result was in agreement with the
´
obtained by Nevesely et al. for oxidation reactions performed in
such solvent mixture to avoid catalyst aggregation.43 Replace-
ment of MeCN : H2O (85 : 15) with EtOH : H2O (95 : 5) as
solvent mixture led to a lower isolated yield (57%) for the same
reaction time (entry 6). Since no bleaching of the RFTA was
observed, the reaction was repeated extending the irradiation
time to 6 h, leading to complete conversion with excellent
chemoselectivity (entry 7). Subsequently, a few control experi-
ments were carried out at longer reaction times. In the absence
of an oxygen atmosphere, photocatalyst or an irradiation
source, the sulfoxide 4a was not produced and the substrate 3a
remains unchanged (entries 8–10). In contrast, when the
photooxidation reaction was carried out in MeCN : H2O
(85 : 15) and air atmosphere excellent conversion and selectivity
was also obtained in 6 h (entry 11). For comparison, the air
atmosphere was also tested in EtOH : H2O (95 : 5) leading to
incomplete conversion even aer 24 h of irradiation (64%, entry
12).
Table 1 Photooxidation of 3a to 4a employing different dyes and
solvents
Entrya
Dye (mol%)
hn (nm)
Solvent
Yield 4ab (%)
1
2
3
4
5
6
7
8
9
10
FL (1)
467
467
467
467
522
522
522
522
522
522
MeCN
i-PrOH
MeCN
i-PrOH
MeCN
i-PrOH
MeCN
i-PrOH
MeCN
i-PrOH
N.R.
N.R.
N.R.
N.R.
16
15
28
37
84
To evidence the formation of singlet oxygen in the media
some additional control reactions were performed. As sodium
azide and 1,4-diazabicyclo[2.2.2]octane (DABCO) are specic
and efficient quenchers of singlet oxygen,45–48 the reactions were
conducted in the presence of these additives. As expected,
formation of the respective sulfoxides 4a was completely
inhibited (entries 13 and 14).
Finally, to determine the scope of the photooxidation reac-
tion, different thiosaccharides 3a–f were oxidized under the
optimized experimental conditions (Table 4).
FLꢀ(21)
FL (1)
FLꢀ2 (1)
EY (1)
EY (1)
RB (1)
RB (1)
R6G (1)
R6G (1)
25
a
Reaction conditions: 3a (0.05 M), solvent (2 mL), 45 ꢁC, irradiated with
blue LED (467 nm) or green LED (522 nm), oxygen atmosphere, 48 h.
b
Determined by 1H NMR. N.R. ¼ no reaction.
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Table 3 Solvent screening and reaction conditions employing RFTA as sensitizer
Entrya
Dye (mol%)
Solvent
Additive
hn (nm)
Atm
Time (h)
Yield 4ab (%)
1
2
3
4
5
6
7
8
RFTA (2)
RFTA (2)
RFTA (2)
RFTA (2)
RFTA (2)
RFTA (2)
RFTA (2)
RFTA (2)
RFTA (2)
—
MeCN
MeOH
EtOH
H2O
—
—
—
—
—
—
—
—
—
—
—
—
NaN3
DABCO
467
467
467
467
467
467
467
467
Dark
467
467
467
467
467
O2
O2
O2
O2
O2
O2
O2
N2
O2
O2
Air
Air
O2
O2
24
24
24
24
2
24
14
25
13
99
57
99
N.R.
N.R.
N.R.
>99
64
MeCN : H2O (85 : 15)
EtOH : H2O (95 : 5)
EtOH : H2O (95 : 5)
MeCN : H2O (85 : 15)
MeCN : H2O (85 : 15)
MeCN : H2O (85 : 15)
MeCN : H2O (85 : 15)
EtOH : H2O (95 : 5)
MeCN : H2O (85 : 15)
MeCN : H2O (85 : 15)
2
6
24
24
24
6
24
24
24
9
10
11
12
13
14
RFTA (2)
RFTA (2)
RFTA (2)
RFTA (2)
N.R.
N.R.
a
b
1
Reaction conditions: 3a (0.05 M), solvent (2 mL), 45 ꢁC. Determined by H NMR. N.R. ¼ no reaction.
As summarized in Table 4, an excellent total isolated yield
Unfortunately, no evidence of an oxidation reaction was
(99%) was obtained for the oxidation of 3a to sulfoxide 4a (entry obtained for the sulde 3e, as this substrate was recovered
1). This was in fact a diastereomeric mixture, which could be unchanged aer 6 h under irradiation (entry 5). Probably the
chromatographically separated affording the SS and SR sulfox- excited state of the photocatalyst is quenched prior to the
ides in 61% and 37% isolated yields, respectively. The photo- formation of singlet oxygen by some interaction with 3e.
oxidation reaction of 3b was also highly efficient, affording the
To evaluate if the studied photochemical reaction could be
diastereomeric mixture of sulfoxides 4b aer 2 h (isolated yield applied to oxidize thiodisaccharides, the compound 3f was
93%). On the other hand, the conversion of substrates 3c and 3d synthesized using a protocol described by our research group.52
was incomplete aer 6 h of irradiation, and the isolated yields The fact that no chemical changes of the thiodisaccharide were
fell to 57% and 60% respectively (entries 3 and 4).
observed during the photooxidation, even aer 24 h of irradi-
These results were not surprising since it was described that ation, indicated that no reaction took place (Table 4, entries 6
C–S bond cleavage can occur when benzyl and allyl suldes and 7). This result may be explained considering the mecha-
undergo photooxidation under singlet oxygen conditions, nism proposed in the bibliography.26,27 The peroxysulfoxide
leading to lower sulfoxide yields.49–51 However, it is important to intermediate generated from the thiodisaccharide 3f needs to
highlight that the photooxidation reaction of the allyl sulde 3d react with another molecule of this compound to afford the
was completely chemoselective, and the sulfoxide 4d was ob- desired sulfoxide. The large steric hindrance produced by the
tained without oxidation of the vinyl group.
sugar groups could prevent the peroxysulfoxide intermediate to
evolve to the sulfoxide and consequently returns to the
Table 4 Scope of the photooxidation reaction employing different per-O-acetylated thiosaccharides under the optimized experimental
conditions
Entrya
Sulde
Time (h)
Conversion (%)
Isolated yield 4b (%)
Diastereomeric ratioc SS/SR
1
2
3
4
5
6
7
3a
3b
3c
3d
3e
3f
2
2
6
6
6
100
100
94
84
0
99
93
57
60
0
1.6/1.0
2.0/1.0
1.5/1.0
1.5/1.0
N.R.
6
24
0
0
0
0
N.R.
N.R.
3f
a
Reaction conditions: 3 (0.05 M), solvent (2 mL), 45 ꢁC, oxygen atmosphere (balloon). b isolated yield. c determined by 1H NMR. N.R. ¼ no reaction.
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obtained. Instead, a complex mixture was formed, probably as
result of radical pathways in the oxidative medium. Most of
these products remained unidentied, although from the
reaction crude, a mixture of both anomers of D-glucopyranose
was isolated as main product (yield 35%, ratio a/b ¼ 1 : 1.6)
(Scheme 3). Similarly, when the free thiodisaccharide 3k was
subjected to the photooxidation a complex mixture was ob-
tained. With the purpose of determining the structure of such
products, the reaction crude was peracetylated employing
pyridine and acetic anhydride (1 : 1), and subsequently sub-
jected to column chromatography purication. The 1H NMR
spectrum of one of the fractions displayed characteristic signals
evidencing the presence of peracetylated glucose (ratio a/b ¼
1 : 1.2). These facts demonstrate that a competitive fragmenta-
tion reaction took place in these cases probably via a radical
cation intermediate generated by the oxidation of the thio-
saccharides 3g–k through an electron transfer reaction (type I
mechanism), which is the main reaction for 3j and 3k.
The stereocontrol in the oxidation reactions was provided by
the asymmetric induction of the glucosyl residue, which favors
the formation of the sulfoxides with SS conguration in almost
all cases.57,58 These results agree with previous reports
describing that thioglycosides with a-conguration lead
predominantly to sulfoxides with the SR absolute conguration
at the sulfur atom, while their b-anomers lead to diastereomeric
mixtures of SS (major) and SR sulfoxides.21,22,59
Scheme 2 De-O-acetylation of thiosaccharides 3a–c, 3e–f.
substrate. Displeased with these results, the removal of the
acetyl protecting group of 3a, 3b, 3c, 3e, and 3f was performed
(Scheme 2), since the oxidation potential of some carbohydrates
can be modied by changing the protecting groups attached to
these molecules.53 The de-O-acetylation reactions were carried
out under mild conditions employing a mixture of MeOH/Et3N/
H2O (4 : 1 : 5)54–56 to afford the free thiosaccharides 3g–k in very
good to excellent isolated yields (90–97%).
With the free thioglycosides in hand, the photooxidation
reactions were conducted under the optimized conditions.
Similar to the photooxidation of its analogue 3a, the sulde 3g
gave excellent results, as the diastereomeric mixture of sulfox-
ides 4g was obtained in 88% isolated yield (ratio SS/SR ¼ 1.5/1)
under irradiation for only 30 min. A mixture of a and b anomers
of D-glucopyranose was also isolated as a minor product (5%).
The diastereomeric mixture of free sulfoxides 4h and 4i were
also obtained in lower reaction times than their peracetylated
analogues, although in lower yields (66 and 53% yield, respec-
tively). In addition, a major amount of D-glucopyranose was also
obtained (Scheme 3).
The conguration at the sulfur stereocenter of each sulfoxide
obtained was established employing the methodology devel-
oped by our research group.18,19 In this protocol, the anisotropic
effect of the S]O group on the chemical shi of specic
protons in the 1H NMR spectra must be considered. To perform
this type of analysis, it is necessary to determine the rotamers,
Unfortunately, the photooxidation reaction of sulde 3j
showed incomplete consumption of the starting material aer
8 h and the corresponding diastereomeric sulfoxides were not
Fig. 1 Conformations displayed by rotation of the anomeric linkage of
b-glucopyranosyl sulfoxides with SR or SS configuration depicted for
the 4C1 chair and in Newman projections.
Scheme 3 Photooxidation reactions of free thiosaccharides 3g–k.
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formed by rotation of the thioglycosidic linkage, present in the although this effect could be partially countered by the protec-
conformational equilibrium. As b-glucopyranosides populate tion effect generated by the proximity to the sulfur lone pair in
4
almost exclusively the C1 conformation, each rotamer is char- the g+ rotamer. The shielding effect observed for the H2 protons
acterized by specic NOE interactions observed in the corre- could be explained by the 1,3-diaxial interaction with the sulfur
sponding 2D-NOESY spectra.
lone pair in the gꢀ rotamer. Furthermore, an additional
As depicted in Fig. 1, in the sulfoxides with the SR congu- shielding contribution should be generated by the proximity of
ration, the rotamer gauche gꢀ is favored because disposes the the sulfur lone pair to H2 in the g+ rotamer, as evidenced in the
residue CH2R in a position with less steric hindrance and it is Newman projection. As consequence of all these effects, the
stabilized by the exo-anomeric effect.
signal of proton H1 in SR sulfoxides are expected to be shied
This was justied by interresidue NOE contacts between the upeld compared to that of H1 in SS sulfoxides, while the
sugar-H1 and the methylene protons of the CH2R observed in the protons H2 are deshielded (higher d value) in the sulfoxides SR
2D-NOESY spectra. The lack of the NOE contact between sugar- sulfoxides compared to SS sulfoxides (Table 5).
H2–CH2R suggested the almost exclusive presence of the gꢀ
Some glycosyl sulfoxides, such as 4aS and 4aR, have been
conformer. On the other hand, in the sulfoxides with the SS previously synthesized.57 The fact that their physical and spec-
conguration, both rotamers gꢀ and g+ are stabilized by tral data agree with those of the same products obtained in this
different factors. The rst one (gꢀ), arranges the residue CH2R in work, and which congurations at the sulfur stereocenter has
a position with less steric hindrance, while the second one (g+) been assigned using the procedure described above, serve as
presents stabilization by the exo-anomeric effect. This fact validation of this methodology developed by us.
explains the coexistence of these two rotamers in equilibrium
Only the peracetylated glucosyl sulfoxides containing R ¼
and was demonstrated by observing the NOE contacts between CH3, could be separated by column chromatography, and all the
sugar-H1–CH2R protons for the gꢀ rotamer, and the spatial other sulfoxide derivates were obtained as their diastereomeric
interaction between sugar-H2–CH2R for the g+ rotamer. These mixtures. Nevertheless, applications of glycosyl sulfoxides as
results are in agreement with those reported by Sanhueza et al. in glycosyl donors allows the use of the diastereomeric mixture,
their study on the stereochemical properties of structurally since the stereochemical outcome in glycosylation reactions is
related glucosyl sulfoxides.60
independent of the sulfoxide stereochemistry (SR or SS).61
Once determined the preferential rotamers, the differences
1
in the chemical shi for signals of specic protons in the H
Experimental
Materials and methods
NMR spectra were analyzed for each sulfoxide. The shielding
and deshielding effects were explained considering the position
of the S]O group and the sulfur lone pair relative to the
protons H1 and H2 of the thiomonosaccharides 4a–d, 4g–i. The
sulfoxides with the SR conguration in the most populated
rotamer gꢀ arranges the lone pair of electrons of the sulfur in
the direction of the H1, generating a shielding effect, while H2
should be deshielded as result of the 1,3-diaxial interaction
between the C2–H2 bond and the S]O group. To perform this
kind of analysis in the sulfoxides with the SS conguration both
rotamers gꢀ and g+ must be considered. In the rotamer gꢀ the
H1 is located in the S]O anisotropic deshielding region,
All photocatalysts were acquired commercially, except for tetra-O-
acetyl riboavin which was synthesized by a known procedure44
from commercially available riboavin. Column chromatography
was carried out with silica gel 60 (230–400 mesh). Analytical thin-
layer chromatography (TLC) was carried out on silica gel 60 F254
aluminium-backed plates (layer thickness 0.2 mm). The spots
were visualized by charring with
a solution of (NH4)6-
Mo7O24$4H2O 25 g Lꢀ1, (NH4)4Ce(SO4)4$2H2O 10 g Lꢀ1 and 10%
H2SO4 in H2O. Nuclear magnetic resonance (NMR) spectra were
recorded at 400 MHz (1H) or 100 MHz (13C). Chemical shis were
calibrated to tetramethylsilane or to a residual solvent peak
(CHCl3: 1H: d ¼ 7.26 ppm, 13C: d ¼ 77.2 ppm or H2O: d ¼
4.79 ppm, respectively). Assignments of 1H and 13C NMR spectra
Table 5 Chemical shift values obtained for H1 and H2 of the glucosyl
sulfoxides 4a–d in CDCl3 and 4g–i in D2O
1
1
were assisted by 2D H-COSY and 2D H–13C HSQC and HMBC
experiments. For the assignment of the NMR signals, the H and C
atoms of the aglycone residue have been labeled as depicted for
each individual compound in the ESI.†
Sulfoxide
dH1 (ppm)
dH2 (ppm)
4a(SR)
4a(SS)
4b(SR)
4b(SS)
4c(SR)
4c(SS)
4d(SR)
4d(SS)
4g(SR)
4g(SS)
4h(SR)
4h(SS)
4i(SR)
4i(SS)
4.15
4.38
4.16
4.34
3.83
4.05
4.16
4.33
4.25
4.63
4.28
4.62
4.07
4.58
5.44
5.06
5.44
5.21
5.44
5.24
5.43
5.34
3.74
3.66
3.74
3.71
3.76
3.64
The coupling constants values are reported in Hz and reso-
nance multiplicities abbreviated as follows: s ¼ singlet, d ¼
doublet, t ¼ triplet, q ¼ quartet, p ¼ pentet, sx ¼ sextet, m ¼
multiplet, br ¼ broad. High-resolution mass spectra (HRMS)
were obtained using the electrospray ionization (ESI) technique
and Q-TOF detection.
Synthetic procedures
General procedure for synthesis of thiomonosaccharides 3a–
d. The b-thioaldose 238 (200 mg, 0.5 mmol) was dissolved in
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acetonitrile (2 mL), triethylamine (380 mL, 2.5 mmol, 5 eq.) and NMR (100 MHz, CDCl3): d ¼ 170.7, 170.3, 169.5 (ꢂ2) (COCH3),
the electrophile (0.55 mmol, 1.1 eq.) were added. The reaction 137.0, 129.2, 128.8, 127.6 (C-aromatics), 82.2 (C-1), 76.0 (C-5),
mixture was stirred at 30 ꢁC for 2 hours, until TLC showed 74.0 (C-3), 70.0 (C-2), 68.6 (C-4), 62.4 (C-6), 34.0 (C-a), 20.9,
complete consumption of the starting materials. The reaction 20.8, 20.7 (ꢂ2) (COCH3) ppm. HRMS (ESI): calcd for
mixture was concentrated under reduced pressure and diluted
C
21H26NaO9S 477.1190 [M + Na]+; found 477.1222.
with EtOAc (50 mL), washed with HCl 0.1 M (20 mL ꢂ 3), dried
Allyl
2,3,4,6-tetra-O-acetyl-1-thio-b-D-glucopyranoside
(3d).
over anhydrous Na2SO4, ltered, and concentrated under Following the general procedure, the synthesis of 3d was carried out
reduced pressure.
adding allyl bromide (47 mL, 0.55 mmol) to the basic solution of 2.
Methyl 2,3,4,6-tetra-O-acetyl-1-thio-b-D-glucopyranoside (3a). The thiosaccharide 3d68 (160 mg, 72%) was obtained as a colorless
Following the general procedure, the synthesis of 3a was per- syrup. Rf ¼ 0.67, hexane/EtOAc (1 : 1). [a]2D5 ¼ ꢀ15.9 (c ¼ 0.9, CHCl3).
formed adding dimethyl sulfate (52 mL, 0.55 mmol) as the 1H NMR (400 MHz, CDCl3): d ¼ 5.81–5.71 (m, 1H, b-H), 5.18 (t, J2,3
¼
electrophile to the basic solution of 2. Upon reaction comple- J3,4 ¼ 9.3 Hz, 1H, 3-H), 5.13–5.08 (m, 2H, c-H, c0-H), 5.02 (t, J3,4 ¼ J4,5
tion, the reaction mixture was diluted with acetonitrile, extrac- ¼ 9.7 Hz, 1H, 4-H), 5.01 (dd, J1,2 ¼ 9.9, J2,3 ¼ 9.4 Hz, 1H, 2-H), 4.45 (d,
ted with hexane (20 mL ꢂ 3) to remove excess of dimethyl J1,2 ¼ 10.1 Hz, 1H, 1-H), 4.19 (dd, J6a,6b ¼ 12.3, J5,6a ¼ 5.2 Hz, 1H, 6a-
sulfate, and then treated as was mentioned above. The thio- H), 4.09 (dd, J6a,6b ¼ 12.3, J5,6b ¼ 2.3 Hz, 1H, 6b-H), 3.62 (ddd, J4,5
saccharide 3a62–64 (205.6 mg, 99%) was obtained as a white solid, 10.0, J5,6a ¼ 5.1, J5,6b ¼ 2.3 Hz, 1H, 5-H), 3.35 (dd, Jgem ¼ 13.5, Ja,b
¼
¼
24
ꢁ
m.p. at 86.8 C (dec.). Rf ¼ 0.60, hexane/EtOAc (1 : 1). [a]D
¼
8.4 Hz, 1H, a-H), 3.19 (dd, Jgem ¼ 13.5, Ja,b ¼ 6.1 Hz, 1H, a-H), 2.04,
ꢀ11.9 (c ¼ 0.8, CHCl3). 1H NMR (400 MHz, CDCl3): d ¼ 5.20 (t, 2.00, 1.98, 1.96 (4s, 12H, COCH3) ppm. 13C NMR (100 MHz, CDCl3):
J2,3 ¼ J3,4 ¼ 9.4 Hz, 1H, 3-H), 5.05 (t, J3,4 ¼ J4,5 ¼ 9.7 Hz, 1H, 4-H), d ¼ 170.6, 170.2, 169.4 (ꢂ2) (COCH3), 133.5 (C-b), 118.0 (C-c), 82.0 (C-
5.04 (t, J1,2 ¼ J2,3 ¼ 9.6 Hz, 1H, 2-H), 4.37 (d, J1,2 ¼ 10.0 Hz, 1H, 1- 1), 75.8 (C-5), 74.0 (C-3), 70.0 (C-2), 68.6 (C-4), 62.3 (C-6), 32.9 (C-a),
H), 4.22 (dd, J6a,6b ¼ 12.4, J5-6a ¼ 4.8 Hz, 1H, 6a-H), 4.12 (dd, 20.7 (ꢂ2), 20.6 (ꢂ2) (COCH3) ppm. HRMS (ESI): calcd for
J6a,6b ¼ 12.4, J5-6b ¼ 1.9 Hz, 1H, 6b-H), 3.71 (ddd, J4,5 ¼ 9.9, J5,6a C17H24NaO9S 427.1033 [M + Na]+; found 427.1014.
¼ 4.5, J5,6b ¼ 2.1 Hz, 1H, 5-H), 2.14 (s, 3H, CH3S), 2.05, 2.04,
Phenyl 2,3,4,6-tetra-O-acetyl-1-thio-b-D-glucopyranoside (3e).
2.00, 1.98 (4s, 12H, COCH3) ppm. 13C NMR (100 MHz, CDCl3): This compound was synthesized employing a procedure previ-
d ¼ 170.8, 170.3, 169.6 (ꢂ2) (COCH3), 83.0 (C-1), 76.1 (C-5), 74.0 ously described.39 To a solution of penta-O-acetyl glucopyranose
(C-3), 69.2 (C-2), 68.4 (C-4), 62.2 (C-6), 20.9, 20.8, 20.7 (ꢂ2) 1 (975 mg, 2.5 mmol) in anhydrous CH2Cl2 (5.0 mL) was added
(COCH3), 11.4 (CH3S) ppm. HRMS (ESI): calcd for C15H22NaO9S thiophenol (0.3 mL, 3 mmol), followed by the dropwise addition
401.0877 [M + Na]+; found 401.0862.
of BF3$OEt2 (1.6 mL, 12.5 mmol) under argon atmosphere. The
Butyl 2,3,4,6-tetra-O-acetyl-1-thio-b-D-glucopyranoside (3b). Following reaction mixture was stirred 4 h until complete consumption of
the general procedure, the synthesis of 3b63,65,66 was performed add- the starting materials. The mixture was diluted to 50 mL in
ing n-butyl bromide (59 mL, 0.55 mmol) to the basic solution of 2. The CH2Cl2 and it was extracted with water (2 ꢂ 50 mL), sodium
thiosaccharide 3b (224 mg, 97%) was obtained as a white solid, m.p. bicarbonate (1 ꢂ 50 mL), and brine (1 ꢂ 50 mL). The organic
69.1–70.0 ꢁC. Rf ¼ 0.75, hexane/EtOAc (1 : 1). [a]2D4 ¼ ꢀ26.9 (c ¼ 0.9, phase was dried over anhydrous Na2SO4, ltered, and concen-
CHCl3). 1H NMR (400 MHz, CDCl3): d ¼ 5.21 (t, J2,3 ¼ J3,4 ¼ 9.4 Hz, trated under reduced pressure. Column chromatography of the
1H, 3-H), 5.07 (t, J3,4 ¼ J4,5 ¼ 9.9 Hz, 1H, 4-H), 5.02 (dd, J1,2 ¼ 10.1, J2,3 residue using pentane/EtOAc (4 : 1 / 1 : 1) afforded 3e63,67,69,70
¼ 9.4 Hz, 1H, 2-H), 4.47 (d, J1,2 ¼ 10.0 Hz, 1H, 1-H), 4.23 (dd, J6a,6b
¼
(782 mg, 71%) as a white solid, m.p. 116.3–117.9 ꢁC. Rf ¼ 0.47,
12.4, J5,6a ¼ 5.0 Hz, 1H, 6a-H), 4.13 (dd, J6a,6b ¼ 12.3, J5,6b ¼ 2.4 Hz, pentane/EtOAc (2 : 1). 1H NMR (400 MHz, CDCl3): d ¼ 7.51–7.48
1H, 6b-H), 3.70 (ddd, J4,5 ¼ 10.0, J5,6a ¼ 4.9, J5,6b ¼ 2.4 Hz, 1H, 5-H), (m, 2H, aromatic), 7.32–7.30 (m, 3H, aromatic), 5.22 (t, J2,3 ¼ J3,4
2.73–2.60 (m, 2H, a-H), 2.07, 2.05, 2.02, 2.00 (4s, 12H, COCH3), 1.60– ¼ 9.3 Hz, 1H, 3-H), 5.04 (t, J3,4 ¼ J4,5 ¼ 9.8 Hz, 1H, 4-H), 4.97 (dd,
1.53 (m, 2H, b-H), 1.39 (sx, Jb,c ¼ Jc,d ¼ 7.4 Hz, 2H, c-H), 0.90 (t, Jc,d
¼
J1,2 ¼ 10.0, J2,3 ¼ 9.3 Hz, 1H, 2-H), 4.71 (d, J1,2 ¼ 10.1 Hz, 1H, 1-
7.3 Hz, 3H, d-H) ppm. 13C NMR (100 MHz, CDCl3): d ¼ 170.8, 170.3, H), 4.22 (dd, J6a,6b ¼ 12.3, J5-6a ¼ 5.0 Hz, 1H, 6a-H), 4.18 (dd,
169.6, 169.5 (COCH3), 83.8 (C-1), 76.0 (C-5), 74.1 (C-3), 70.0 (C-2), 68.5 J6a,6b ¼ 12.3, J5,6b ¼ 2.6 Hz, 1H, 6b-H), 3.72 (ddd, J4,5 ¼ 10.0, J5,6a
(C-4), 62.3 (C-6), 31.8 (C-b), 29.8 (C-a), 22.0 (C-c), 20.9 (ꢂ2), 20.7 (ꢂ2) ¼ 5.0, J5,6b ¼ 2.7 Hz, 1H, 5-H), 2.08 (ꢂ2), 2.01, 1.99 (4s, 12H,
(COCH3), 13.7 (C-d) ppm. HRMS (ESI): calcd for C18H28NaO9S COCH3) ppm. 13C NMR (100 MHz, CDCl3): d ¼ 170.7, 170.3,
443.1346 [M + Na]+; found 443.1357.
169.5, 169.4 (COCH3), 133.3, 131.8, 129.1, 128.6 (aromatic), 85.9
Benzyl 2,3,4,6-tetra-O-acetyl-1-thio-b-D-glucopyranoside (3c). (C-1), 76.0 (C-5), 74.1 (C-3), 70.1 (C-2), 68.4 (C-4), 62.3 (C-6), 20.9,
Following the general procedure, the synthesis of 3c was per- 20.8, 20.7 (ꢂ2) (COCH3) ppm. HRMS (ESI): calcd for
formed adding benzyl bromide (65 mL, 0.55 mmol) to the basic
solution of 2. The thiosaccharide 3c63,66,67 (215 mg, 86%) was
C
20H24NaO9S 463.1033 [M + Na]+; found 463.0989.
Benzyl 3-deoxy-2,6-di-O-acetyl-4-S-(2,3,4,6-tetra-O-acetyl-b-D-gluco-
obtained as a white solid, m.p. at 93.8 ꢁC (dec.). Rf ¼ 0.65, pyranosyl)-4-thio-a-D-xylo-hexopyranoside (3f). Thiodisaccharide 3f
1
hexane/EtOAc (1 : 1). [a]2D4 ¼ ꢀ86.5 (c ¼ 1.0, CHCl3). H NMR was obtained following a protocol described by our research group52
ꢁ
(400 MHz, CDCl3): d ¼ 7.34–7.29 (m, 5H, PhCH2O), 5.16–5.04 as a white solid, m.p. at 110 C (dec.). Rf ¼ 0.53 (pentane/EtOAc,
(m, 3H, 3-H, 2-H, 4-H), 4.29 (d, J1,2 ¼ 9.7 Hz, 1H, 1-H), 4.23 (dd, 1 : 1). [a]2D5 ¼ +28.5 (c ¼ 1.2, CHCl3) H NMR (400 MHz, CDCl3):
1
J6a,6b ¼ 12.4, J5,6a ¼ 5.1 Hz, 1H, 6a-H), 4.13 (dd, J6a,6b ¼ 12.3, J5,6b d ¼ 7.36–7.29 (m, 5H, aromatic), 5.21 (m, 2H, 2-H, 30-H), 5.08 (t, J3 ,4
0
0
¼ 2.2 Hz, 1H, 6b-H), 3.94 (d, Jgem ¼ 12.9 Hz, 1H, a-H), 3.83 (d, ¼ J4 ,5 ¼ 9.7 Hz, 1H, 40-H), 5.01 (t, J1 ,2 ¼ J2 ,3 ¼ 9.6 Hz, 1H, 20-H),
0
0
0
0
0
0
Jgem ¼ 12.9 Hz, 1H, a-H), 3.59 (ddd, J4,5 ¼ 9.6, J5,6a ¼ 5.0, J5,6b
¼
5.01 (d, J1,2 ¼ 3.2 Hz, 1H, 1-H), 4.74 (d, Jgem ¼ 12.0 Hz, 1H, PhCH2O),
2.3 Hz, 1H, 5-H), 2.11, 2.01 (ꢂ2), 1.99 (4s, 12H, COCH3) ppm. 13
C
4.61 (d, J1 ,2 ¼ 10.0 Hz, 1H, 10-H), 4.52 (d, Jgem ¼ 12.0 Hz, 1H,
0
0
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0
0
0
0
PhCH2O), 4.36 (m, 1H, 5-H), 4.21 (dd, J6 a,6 b ¼ 12.5, J5 ,6 a ¼ 4.6 Hz, 13.3 Hz, 1H, a-H), 3.88 (dd, J6a,6b ¼ 12.5, J5,6a ¼ 2.1 Hz, 1H, 6a-
1H, 60a-H), 4.16 (m, 2H, 6a-H, 6b-H), 4.13 (dd, J6 a,6 b ¼ 12.5, J5 ,6 b
¼
H), 3.71 (dd, J6a,6b ¼ 12.5, J5,6b ¼ 5.6 Hz, 1H, 6b-H), 3.44–3.34 (m,
0
0
0
0
2.3 Hz, 1H, 60b-H), 3.67 (ddd, J4 ,5 ¼ 9.9, J5 ,6 a ¼ 4.4, J5 ,6 b ¼ 2.4 Hz, 4H, 4-H, 3-H, 2-H, 5-H) ppm. 13C NMR (100 MHz, D2O): d ¼
0
0
0
0
0
0
1H, 50-H), 3.39 (br d, J ¼ 2.1 Hz, 1H, 4-H), 2.34 (td, J2,3a ¼ J3a,3b
¼
138.0, 129.1, 128.8, 127.4 (aromatic), 84.0 (C-1), 79.8(C-5),
12.6, J3a,4 ¼ 3.6 Hz, 1H, 3a-H), 2.14 (m, 1H, 3b-H), 2.07, 2.06 (ꢂ2), 77.3(C-3), 72.2 (C-2), 69.5(C-4), 60.9 (C-6), 33.6 (C-a) ppm.
2.03, 2.01, 1.99 (COCH3) ppm. 13C NMR (100 MHz, CDCl3): d ¼ HRMS (ESI): calcd for C13H18NaO5S 309.0767 [M + Na]+; found
170.7, 170.6, 170.2 (ꢂ2), 169.7, 169.4 (COCH3), 137.3, 128.6, 128.1, 309.0770.
128.0 (C-Ph), 94.9 (C-1), 82.8 (C-10), 76.1 (C-50), 73.9 (C-30), 70.0 (C-20),
Phenyl 1-thio-b-D-glucopyranoside (3j). The thiosaccharide 3e
69.2 (PhCH2O), 68.3 (ꢂ2, C-40, C-5), 66.9 (C-2), 65.4 (C-6), 62.0 (C-60), (44.1 mg, 0.1 mmol) was dissolved in MeOH/Et3N/H2O (4 : 1 : 5,
ꢁ
42.9 (C-4), 30.9 (C-3), 21.1, 20.9, 20.8, 20.7 (ꢂ3) (COCH3). HRMS 0.55 mL) and the reaction mixture was stirred at 30 C for 3 h.
(ESI): calcd for C31H40NaO15S 707.1980 [M + Na]+; found 707.1959. Aer TLC showed complete consumption of the starting mate-
Synthesis of unprotected thiosaccharides 3g–k
rial, the mixture was concentrated under reduced pressure and
Methyl 1-thio-b-D-glucopyranoside (3g). The thiosaccharide 3a the residue was puried by column chromatography using
(37.8 mg, 0.1 mmol) was dissolved in MeOH/Et3N/H2O (4 : 1 : 5, CH2Cl2/MeOH (4 : 1 / 2 : 1), affording 3j74,75 (24.5 mg, 91%) as
ꢁ
ꢁ
0.55 mL) and the reaction mixture was stirred at 30 C for 2 h. a white solid, m.p. at 128.5 C (dec.). Rf ¼ 0.66, CH2Cl2/MeOH
When TLC showed complete consumption of the starting (4 : 1). [a]2D4 ¼ +49.2 (c ¼ 1.0, EtOH) 1H NMR (400 MHz, D2O): d ¼
material, the mixture was concentrated under reduced pressure. 7.65–7.63 (m, 3H, aromatic), 7.50–7.44 (m, 3H, aromatic), 4.85
Column chromatography using CH2Cl2/MeOH (4 : 1 / 2 : 1) (d, J1,2 ¼ 9.9 Hz, 1H, 1-H), 3.95 (dd, J6a,6b ¼ 12.5, J5-6a ¼ 2.2 Hz,
afforded 3g71–73 (18.9 mg, 90%) as a colorless syrup. Rf ¼ 0.40, 1H, 6a-H), 3.77 (dd, J6a,6b ¼ 12.5, J5-6b ¼ 5.6 Hz, 1H, 6b-H), 3.58
CH2Cl2/MeOH (4 : 1). [a]2D3 ¼ ꢀ17.2 (c ¼ 1.1, H2O) 1H NMR (400 (t, J2,3 ¼ J3,4 ¼ 8.9 Hz, 1H, 3-H), 3.56–3.51 (m, 1H, 5-H), 3.47 (dd,
MHz, D2O): d ¼ 4.49 (d, J1,2 ¼ 9.8 Hz, 1H, 1-H), 3.96 (dd, J6a,6b
12.4, J5,6a ¼ 2.1 Hz, 1H, 6a-H), 3.77 (dd, J6a,6b ¼ 12.5, J5,6b
¼
¼
J4,5 ¼ 9.7, J3,4 ¼ 9.0 Hz, 1H, 4-H), 3.41 (dd, J1,2 ¼ 9.8, J2,3 ¼
9.0 Hz, 1H, 2-H) ppm. 13C NMR (100 MHz, D2O): d ¼ 132.0,
5.6 Hz, 1H, 6b-H), 3.55 (t, J2,3 ¼ J3,4 ¼ 8.8 Hz, 1H, 3-H), 3.54–3.50 131.7, 129.4, 128.1 (aromatic), 87.3 (C-1), 79.9 (C-5), 77.3 (C-3),
(m, 1H, 5-H), 3.46 (dd, J3,4 ¼ 8.9, J4,5 ¼ 9.6 Hz, 1H, 4-H), 3.41 (dd, 71.8 (C-2), 69.4 (C-4), 60.9 (C-6) ppm. HRMS (ESI): calcd for
J1,2 ¼ 9.7, J2,3 ¼ 8.8 Hz, 1H, 2-H), 2.27 (s, 3H, CH3S) ppm. 13C
NMR (100 MHz, D2O): d ¼ 85.6 (C-1), 79.9 (C-5), 77.2 (C-3), 71.7
C
12H16NaO5S 295.0611 [M + Na]+; found 295.0619.
Benzyl
3-deoxy-4-S-(b-D-glucopyranosyl)-4-thio-a-D-xylo-hex-
(C-2), 69.6 (C-4), 60.9 (C-6), 11.4 (CH3S) ppm. HRMS (ESI): calcd opyranoside (3k). The thiodisaccharide 3f (68.4 mg, 0.1 mmol)
for C7H14NaO5S 233.0454 [M + Na]+; found 233.0447.
was dissolved in MeOH/Et3N/H2O (4 : 1 : 5, 0.84 mL) and the
Butyl 1-thio-b-D-glucopyranoside (3h). The thiosaccharide 3b reaction mixture was stirred at 30 ꢁC for 3 h. When TLC showed
(538.0 mg, 1.28 mmol) was dissolved in MeOH/Et3N/H2O complete consumption of the starting material into a more
ꢁ
(4 : 1 : 5, 7.2 mL) and the reaction mixture was stirred at 30 C polar product (Rf ¼ 0.74, BuOH/EtOH/H2O (10 : 4 : 4)), the
for 3 h. When TLC showed complete consumption of the mixture was concentrated under reduced pressure. Subse-
starting material, the mixture was concentrated under reduced quently, purication of the residue by column chromatography
pressure. Column chromatography using CH2Cl2/MeOH (8 : 1) using CH2Cl2/MeOH (4 : 1 / 2 : 1) afforded 3k (40.2 mg, 93%)
afforded 3h (312 mg, 97%) as a colorless syrup. Rf ¼ 0.78, as a colorless syrup. 1H NMR (400 MHz, D2O): d ¼ 7.55–7.44 (m,
1
CH2Cl2/MeOH (4 : 1). [a]2D3 ¼ ꢀ40.1 (c ¼ 1.2, MeOH) H NMR 5H, aromatic), 5.02 (d, J1,2 ¼ 3.9 Hz, 1H, 1-H), 4.84 (d, Jgem
¼
(400 MHz, D2O): d ¼ 4.55 (d, J1,2 ¼ 9.9 Hz, 1H, 1-H), 3.93 (dd, 11.7 Hz, 1H, PhCH2O), 4.71 (d, Jgem ¼ 11.8 Hz, 1H, PhCH2O),
J6a,6b ¼ 12.4, J5,6a ¼ 1.6 Hz, 1H, 6a-H), 3.73 (dd, J6a,6b ¼ 12.4, J5,6b 4.64 (d, J1 ,2 ¼ 9.8 Hz, 1H, 10-H), 4.26–4.16 (m, 2H, 5-H, 2-H),
0
0
¼ 5.5 Hz, 1H, 6b-H), 3.51 (t, J2,3 ¼ J3,4 ¼ 8.6 Hz, 1H, 3-H), 3.48 3.95 (dd, J6 a,6 b ¼ 12.3 Hz, J5 ,6 a ¼ 2.0 Hz, 1H, 60a-H), 3.77 (dd,
0
0
0
0
0
0
(ddd, J4,5 ¼ 9.4, J5,6b ¼ 5.4, J5,6a ¼ 1.6 Hz, 1H, 5-H), 3.43 (t, J3,4
¼
J6a,6b ¼ 11.8, J5,6a ¼ 5.0 Hz, 1H, 6a-H), 3.75 (dd, J6 a,6 b ¼ 12.4,
J4,5 ¼ 9.3 Hz, 1H, 4-H), 3.34 (t, J1,2 ¼ J2,3 ¼ 9.3 Hz, 1H, 2-H), 2.85– J5 ,6 b ¼ 5.4 Hz, 1H, 60b-H), 3.63 (dd, J6a,6b ¼ 11.8, J5,6b ¼ 7.4 Hz,
0
0
2.72 (m, 2H, a-H), 1.65 (p, Ja,b ¼ Jb,c ¼ 7.4 Hz, 2H, b-H), 1.43 (sx, 1H, 6b-H), 3.58–3.43 (m, 4H, 4-H, 30-H, 40-H, 50-H), 3.36 (dd, J1 ,2
0
0
Jb,c ¼ Jc,d ¼ 7.4 Hz, 2H, c-H), 0.92 (t, Jc,d ¼ 7.4 Hz, 3H, d-H) ppm. ¼ 9.7, J2 ,3 ¼ 8.9 Hz, 1H, 20-H), 2.29–2.16 (m, 2H, 3a-H, 3b-
13C NMR (100 MHz, D2O): d ¼ 85.4 (C-1), 79.9 (C-5), 77.3 (C-3), H) ppm. 13C NMR (100 MHz, D2O): d ¼ 137.3, 128.8, 128.7, 128.4
72.4 (C-2), 69.6 (C-4), 61.0 (C-6), 31.5 (C-b), 29.7 (C-a), 21.3 (C- (aromatic), 97.5 (C-1), 84.9 (C-10), 80.0 (C-40), 77.3 (C-30), 72.6 (C-
c), 12.9 (C-d) ppm. HRMS (ESI): calcd for C10H20NaO5S 20), 70.6 (C-5), 69.8 (PhCH2O), 69.6 (C-50), 64.2 (C-2), 62.5 (C-6),
0
0
275.0924 [M + Na]+; found 275.0929.
61.0 (C-60), 42.9 (C-4), 32.7 (C-3) ppm. HRMS (ESI): calcd for
C
Benzyl 1-thio-b-D-glucopyranoside (3i). The thiosaccharide 3c
19H28NaO9S 455.1346 [M + Na]+; found 455.1369.
(260.0 mg, 0.57 mmol) was dissolved in MeOH/Et3N/H2O
General procedure for the photooxidation of glucopyranosyl
ꢁ
(4 : 1 : 5, 3.2 mL) and the reaction mixture was stirred at 30 C suldes. Sulde 3a–k (0.1 mmol) and the photocatalyst (1–
for 3 h. When TLC showed complete consumption of the 10 mol%, 0.001–0.01 mmol) were dissolved in the solvent
starting material, the mixture was concentrated under reduced mixture in a glass vial, equipped with a rubber septum and
pressure. Column chromatography using CH2Cl2/MeOH (8 : 1) a magnetic stirrer. The reaction mixture was saturated with
afforded 3i (152.3 mg, 93%) as a colorless syrup. Rf ¼ 0.82, oxygen by bubbling with a balloon for 5 minutes and irradiated
1
CH2Cl2/MeOH (4 : 1). [a]D23 ¼ ꢀ129.4 (c ¼ 1.0, MeOH) H NMR with a 3 W LED with continuous stirring. The average temper-
(400 MHz, D2O): d ¼ 7.45–7.35 (m, 5H, aromatic), 4.34 (d, J1,2
9.4 Hz, 1H, 1-H), 4.05 (d, Jgem ¼ 13.2 Hz, 1H, a-H), 3.96 (d, Jgem
¼
¼
ature value in the reaction vial was determined to be 42 ꢁC. The
balloon was le to ensure constant supply of oxygen into the
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reaction vial. The reaction course was monitored by TLC for R isomer: d ¼ 5.44 (dd, J1,2 ¼ 9.8, J2,3 ¼ 9.4 Hz, 1H, 2-HR), 5.35
(hexane/EtOAc, 1 : 1). For sulfoxides 4a–d, the reaction mixtures (t, J2,3 ¼ J3,4 ¼ 9.3 Hz, 1H, 3-HR), 5.12 (dd, J4,5 ¼ 10.0, J3,4
¼
were puried by column chromatography with hexane/EtOAc 9.5 Hz, 1H, 4-HR overlapping with 4-HS of 4bS), 4.27–4.21 (m,
(8 : 1 / 1 : 1), while sulfoxides 4g–i were puried using 2H, 6a-HR, 6b-HR), 4.16 (d, J1,2 ¼ 9.9 Hz, 1H, 1-HR), 3.82–3.78 (m,
MeCN/H2O (9 : 1 / 4 : 1) or CH2Cl2/MeOH (8 : 1 / 4 : 1).
1H, 5-HR,overlapping with 5-HS of 4bS), 3.16–3.09 (m, 1H, a-HR),
Methyl 2,3,4,6-tetra-O-acetyl-1-thio-b-D-glucopyranoside (S)-S- 2.74–2.67 (m, 1H, a-HR), 2.07–2.01 (4s, 12H, COCH3 overlapping
oxide (4aS). The major product of the oxidation of thio- with COCH3 of 4bS), 1.79–1.73 (m, 2H, b-HR overlapping with b-
saccharide 3a was sulfoxide 4aS57 (24 mg, 61%) obtained as HS of 4bS), 1.57–1.43 (m, 2H, c-HR overlapping with c-HS of 4bS),
a colorless syrup. Rf ¼ 0.25, EtOAc. [a]2D3 ¼ ꢀ12.2 (c ¼ 0.9, 0.96 (t, Jc,d ¼ 7.3 Hz, 3H, d-HR overlapping with d-HS of
CHCl3). 1H NMR (400 MHz, CDCl3): d ¼ 5.31 (t, J2,3 ¼ J3,4
¼
4bS) ppm. 13C NMR (100 MHz, CDCl3) data for R isomer: d ¼
9.3 Hz, 1H, 3-H), 5.11 (dd, J4,5 ¼ 9.9, J3,4 ¼ 9.6 Hz, 1H, 4-H), 5.07 170.6–168.9 (COCH3 overlapping with COCH3 of 4bS), 87.0 (C-
(dd, J1,2 ¼ 10.0, J2,3 ¼ 9.4 Hz, 1H, 2-H), 4.38 (d, J1,2 ¼ 10.2 Hz, 1H, 1R), 77.0 (C-5R), 73.9 (C-3R), 68.0 (C-4R), 67.0 (C-2R), 62.1 (C-6R),
1-H), 4.32 (dd, J6a,6b ¼ 12.6, J5,6a ¼ 4.5 Hz, 1H, 6a-H), 4.21 (dd, 47.1 (C-aR), 24.9 (C-bR), 22.3 (C-cR), 20.8–20.7 (COCH3 over-
J6a,6b ¼ 12.6, J5,6b ¼ 2.2 Hz, 1H, 6b-H), 3.84 (ddd, J4,5 ¼ 10.1, J5,6a lapping with COCH3 of 4bS), 13.8 (C-dR overlapping with C-dS of
¼ 4.5, J5,6b ¼ 2.2 Hz, 1H, 5-H), 2.68 (s, 3H, CH3SO), 2.09, 2.07, 4bS) ppm. HRMS (ESI): calcd for C18H28NaO10S 459.1295 [M +
2.04, 2.02 (4s, 12H, COCH3) ppm. 13C NMR (100 MHz, CDCl3): Na]+; found 459.1271.
d ¼ 170.6, 170.1, 169.9, 169.5 (COCH3), 90.9 (C-1), 77.0 (C-5),
Benzyl 2,3,4,6-tetra-O-acetyl-1-thio-b-D-glucopyranoside (R,S)-S-
73.3 (C-3), 68.4 (C-2), 67.8 (C-4), 61.5 (C-6), 33.0 (CH3SO), 20.8, oxide (4cR,S). The oxidation reaction of thiosaccharide 3c gave
20.7 (ꢂ3) (COCH3) ppm. HRMS (ESI): calcd for C15H22NaO10S the diastereomeric mixture of sulfoxides 4cR,S76 that could not
417.0826 [M + Na]+; found 417.0756.
be separated by column chromatography. The mixture (26.8 mg,
Methyl 2,3,4,6-tetra-O-acetyl-1-thio-b-D-glucopyranoside (R)-S- 57%, ratio S/R, 1.5 : 1) was obtained as a white solid and showed
oxide (4aR). The minor product of the oxidation of thio- a single spot in TLC analysis. Rf ¼ 0.12, hexane/EtOAc (1 : 1). 1H
saccharide 3a was sulfoxide 4aR57 (14.6 mg, 36%) obtained as NMR (400 MHz, CDCl3) data for S isomer: d ¼ 7.41–7.32 (m, 5H,
a colorless syrup. Rf ¼ 0.20, EtOAc. [a]D23 ¼ ꢀ64.7 (c ¼ 0.8, aromaticS overlapping with aromaticR of 4cR), 5.28 (t, J1,2 ¼ J2,3
CHCl3). 1H NMR (400 MHz, CDCl3): d ¼ 5.44 (t, J1,2 ¼ J2,3
¼
¼ 9.3 Hz, 1H, 2-HS), 5.24 (t, J2,3 ¼ J3,4 ¼ 9.1 Hz, 1H, 3-HS), 5.14–
9.6 Hz, 1H, 2-H), 5.36 (t, J2,3 ¼ J3,4 ¼ 9.3 Hz, 1H, 3-H), 5.15 (dd, 5.07 (m, 1H, 4-HS overlapping with 4-HR of 4cR), 4.33–4.26 (m,
J4,5 ¼ 9.9, J3,4 ¼ 9.4 Hz, 1H, 4-H), 4.27 (dd, J6a,6b ¼ 12.7, J5,6a
5.1 Hz, 1H, 6a-H), 4.23 (dd, J6a,6b ¼ 12.7, J5,6b ¼ 3.0 Hz, 1H, 6b- J5,6b ¼ 2.4 Hz, 1H, 6b-HS), 4.16 (d, Jgem ¼ 13.0 Hz, 1H, a-HS), 4.16
H), 4.15 (d, J1,2 ¼ 9.8 Hz, 1H, 1-H), 3.82 (ddd, J4,5 ¼ 10.1, J5,6a (d, J1,2 ¼ 9.8 Hz, 1H, 1-HS), 4.07 (d, Jgem ¼ 13.0 Hz, 1H, a-HS),
¼
1H, 6a-HS overlapping with 6b-HR, a-HR), 4.24 (dd, J6a,6b ¼ 12.6,
¼
4.9, J5,6b ¼ 2.9 Hz, 1H, 5-H), 2.69 (s, 3H, CH3SO), 2.08, 2.06, 2.05, 3.77 (ddd, J4,5 ¼ 9.9, J5,6a ¼ 4.6, J5,6b ¼ 2.3 Hz, 1H, 5-HS), 2.16–
2.03 (4s, 12H, COCH3) ppm. 13C NMR (100 MHz, CDCl3): d ¼ 2.00 (4s, 12H, COCH3 overlapping with COCH3 of 4cR) ppm. 13
C
170.7, 170.6, 169.3, 169.1 (COCH3), 87.6 (C-1), 77.0 (C-5), 73.8 (C- NMR (100 MHz, CDCl3) data for S isomer: d ¼ 170.6–168.7
3), 67.9 (C-4), 67.0 (C-2), 62.0 (C-6), 33.2 (CH3SO), 20.8 (ꢂ2), 20.7 (COCH3 overlapping with COCH3 of 4cR), 130.7–128.7
(ꢂ2) (COCH3) ppm. HRMS (ESI): calcd for C15H22NaO10S (aromaticS overlapping with aromaticR of 4cR), 88.9 (C-1S), 76.9
417.0826 [M + Na]+; found 417.0798.
(C-5S), 73.2 (C-3S), 68.6 (C-2S), 67.9 (C-4S), 61.7 (C-6S), 53.8 (C-aS),
Butyl 2,3,4,6-tetra-O-acetyl-1-thio-b-D-glucopyranoside (R,S)-S- 20.9–20.6 (COCH3 overlapping with COCH3 of 4cR) ppm. 1H
oxide (4bR,S). The oxidation reaction of thiosaccharide 3b gave NMR (400 MHz, CDCl3) data for R isomer: d ¼ 7.41–7.31 (m, 5H,
the diastereomeric mixture of sulfoxides 4bR,S that could not be aromaticR overlapping with aromaticS of 4cS), 5.44 (dd, J1,2
¼
separated by column chromatography. The mixture (40.5 mg, 10.1, J2,3 ¼ 9.3 Hz, 1H, 2-HR), 5.22 (t, J2,3 ¼ J3,4 ¼ 9.3 Hz, 1H, 3-
93%, ratio S/R, 2 : 1) was obtained as a white solid and showed HR), 5.14–5.07 (m, 1H, 4-HR overlapping with 4-HS of 4cS), 4.41
a single spot by TLC analysis. Rf ¼ 0.17, hexane/EtOAc (1 : 1). 1H (d, Jgem ¼ 12.3 Hz, 1H, a-HR), 4.35 (dd, J6a,6b ¼ 12.5, J5,6a
¼
NMR (400 MHz, CDCl3) data for S isomer: d ¼ 5.29 (t, J2,3 ¼ J3,4
¼
2.5 Hz, 1H, 6a-HR), 4.33–4.26 (m, 2H, 6b-HR, a-HR overlapping
9.2 Hz, 1H, 3-HS), 5.21 (t, J1,2 ¼ J2,3 ¼ 9.6 Hz, 1H, 2-HS), 5.09 (dd, with 6a-HS of 4cS), 3.83 (d, J1,2 ¼ 10.2 Hz, 1H, 1-HR), 3.73 (ddd,
J4,5 ¼ 9.7, J3,4 ¼ 9.4 Hz, 1H, 4-HS overlapping with 4-HR of 4bR), J4,5 ¼ 10.0, J5,6a ¼ 6.1, J5,6b ¼ 2.3 Hz, 1H, 5-HR), 2.16–2.00 (4s,
4.34 (d, J ¼ 9.9 Hz, 1H, 1-HS), 4.27 (dd, J6a,6b ¼ 12.6, J5,6a
¼
12H, COCH3 overlapping with COCH3 of 4cS) ppm. 13C NMR
4.6 Hz, 1H, 6a-HS), 4.17 (dd, J6a,6b ¼ 12.6, J5,6b ¼ 2.3 Hz, 1H, 6b- (100 MHz, CDCl3) data for R isomer: d ¼ 170.6–168.7 (COCH3
HS), 3.82–3.78 (m, 1H, 5-HS,overlapping with 5-HR of 4bR), 2.96– overlapping with COCH3 of 4cS), 130.7–128.7 (aromaticR over-
2.89 (m, 1H, a-HS), 2.83–2.76 (m, 1H, a-HS), 2.07–2.01 (4s, 12H, lapping with aromaticS of 4cS), 84.6 (C-1R), 77.1 (C-5R), 73.9 (C-
COCH3 overlapping with COCH3 of 4bR), 1.79–1.73 (m, 2H, b-HS 3R), 68.1 (C-4R), 66.5 (C-2R), 62.6 (C-6R), 53.5 (C-aR), 20.9–20.6
overlapping with b-HR of 4bR), 1.57–1.43 (m, 2H, c-HS over- (COCH3 overlapping with COCH3 of 4cS) ppm. HRMS (ESI):
lapping with c-HR of 4bR), 0.96 (t, Jc,d ¼ 7.3 Hz, 3H, d-HS over- calcd for C21H26NaO10S 493.1139 [M + Na]+; found 493.1115.
lapping with d-HR of 4bR) ppm. 13C NMR (100 MHz, CDCl3) data
Allyl 2,3,4,6-tetra-O-acetyl-1-thio-b-D-glucopyranoside (R,S)-S-
for S isomer: d ¼ 170.6–168.9 (COCH3 overlapping with COCH3 oxide (4dR,S). The oxidation reaction of thiosaccharide 3d gave
of 4bR), 90.4 (C-1S), 77.0 (C-5S), 73.3 (C-3S), 68.5 (C-2S), 67.8 (C- the diastereomeric mixture of sulfoxides 4dR,S that could not
4S), 61.6 (C-6S), 47.2 (C-aS), 24.2 (C-bS), 22.1 (C-cS), 20.8–20.7 be separated by column chromatography. The mixture (25.3 mg,
(COCH3 overlapping with COCH3 of 4bR), 13.8 (C-dS over- 60%, ratio S/R, 1.5 : 1) was obtained as a white solid and showed
1
lapping with C-dR of 4bR) ppm. 1H NMR (400 MHz, CDCl3) data a single spot by TLC. Rf ¼ 0.10, hexane/EtOAc (1 : 1). H NMR
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(400 MHz, CDCl3) data for S isomer: d ¼ 6.00–5.89 (m, 1H, b-HS), 1-HS), 3.96 (dd, J6a,6b ¼ 12.6, J5,6a ¼ 2.1 Hz, 1H, 6a-HS), 3.79 (dd,
5.51–5.41 (m, 2H, c-HS, c0-HS overlapping with c-HR, c0-HR, 2-HR J6a,6b ¼ 12.8, J5,6b ¼ 6.1 Hz, 1H, 6b-HS), 3.71 (t, J1,2 ¼ J2,3
¼
of 4dR), 5.34 (t, J1,2 ¼ J2,3 ¼ 9.2 Hz, 1H, 2-HS), 5.29 (t, J2,3 ¼ J3,4
¼
9.3 Hz, 1H, 2-HS), 3.64 (t, J2,3 ¼ J3,4 ¼ 9.0 Hz, 1H, 3-HS), 3.59
9.1 Hz, 1H, 3-HS), 5.08 (t, J3,4 ¼ J4,5 ¼ 9.2 Hz, 1H, 4-HS), 4.33 (d, (ddd, J4,5 ¼ 9.7, J5,6b ¼ 5.9, J5,6a ¼ 2.1 Hz, 1H, 5-Hs), 3.46 (br t, J3,4
J1,2 ¼ 9.4 Hz, 1H, 1-HS), 4.28–4.22 (m, 1H, 6a-HS overlapping ¼ J4,5 ¼ 9.4 Hz, 1H, 3-Hs), 3.30–3.23 (m, 1H, a-Hs overlapping
with 6a-HR, 6b-HR, 1-HR of 4dR), 4.19 (dd, J6a,6b ¼ 12.6, J5,6b
¼
with a-HR of 4hR), 3.02–2.93 (m, 1H, a-Hs overlapping with a-HR
2.1 Hz, 1H, 6b-HS), 3.80–3.76 (m, 1H, 5-HS overlapping with 5- of 4hR), 1.85–1.66 (m, 2H, b-Hs overlapping with b-HR of 4hR)
HR of 4dR), 3.66 (dd, Jgem ¼ 13.3, Ja,b ¼ 7.0 Hz, 1H, a-HS), 3.57 1.60–1.45 (m, 2H, c-Hs overlapping with c-HR of 4hR), 0.97(t, Jc,d
(dd, Jgem ¼ 13.1, Ja,b ¼ 8.0 Hz, 1H, a-HS), 2.09–2.02 (4s, 12H, ¼ 7.3 Hz, 3H, d-Hs) ppm. 13C NMR (100 MHz, D2O) data for S
COCH3 overlapping with COCH3 of 4dR) ppm. 13C NMR (100 isomer: d ¼ 90.8 (C-1S), 80.8 (C-5S), 77.2 (C-3S), 69.1 (C-2S), 68.9
MHz, CDCl3) data for S isomer: d ¼ 170.5–168.8 (COCH3 over- (C-4S), 60.8 (C-6S), 44.8 (C-aS), 24.1 (C-bs overlapping with C-bR),
lapping with COCH3 of 4dR), 125.5 (C-bS), 124.3 (C-cS), 89.0 (C- 21.2 (C-cS), 12.9 (C-ds) ppm. 1H NMR (400 MHz, D2O) data for R
1S), 76.9 (C-5S), 73.3 (C-3S), 68.6 (C-2S), 67.8 (C-4S), 61.7 (C-6S), isomer: d ¼ 4.28 (d, J1,2 ¼ 9.8 Hz, 1H, 1-HR), 3.97 (dd, J6a,6b
¼
52.0 (C-aS), 20.8–20.6 (COCH3 overlapping with COCH3 of 12.7, J5,6a ¼ 2.2 Hz, 1H, 6a-HR), 3.83 (dd, J6a,6b ¼ 13.0, J5,6b
¼
1
4dR) ppm. H NMR (400 MHz, CDCl3) data for R isomer: d ¼ 5.1 Hz, 1H, 6b-HR), 3.74 (t, J1,2 ¼ J2,3 ¼ 9.7 Hz, 1H, 2-HR), 3.66 (t,
5.84–5.73 (m, 1H, b-HR), 5.51–5.41 (m, 3H, c-HR, c0-HR, 2-HR J2,3 ¼ J3,4 ¼ 8.7 Hz, 1H, 3-HR), 3.64–3.59 (m, 1H, 5-HR), 3.52 (br t,
overlapping with c-HS, c0-HS of 4dS), 5.35 (t, J2,3 ¼ J3,4 ¼ 9.3 Hz, J3,4 ¼ J4,5 ¼ 9.4 Hz, 1H, 3-HR), 3.30–3.23 (m, 1H, a-HR over-
1H, 3-HR), 5.11 (t, J3,4 ¼ J4,5 ¼ 9.7 Hz, 1H, 4-HR), 4.28–4.22 (m, lapping with a-HS of 4hS), 3.02–2.93 (m, 1H, a-HR overlapping
3H, 6a-HR, 6b-HR, 1-HR overlapping with 6a-HS of 4dS), 3.83 (dd, with a-HS of 4hS), 1.85–1.66 (m, 2H, b-HR overlapping with b-HS
Jgem ¼ 12.7, Ja,b ¼ 9.0 Hz, 1H, a-HR), 3.80–3.76 (m, 1H, 5-HR of 4hS) 1.60–1.45 (m, 2H, c-HR overlapping with c-HS of 4hS),
overlapping with 5-HS of 4dS), 3.75 (dd, Jgem ¼ 12.6, Ja,b
¼
0.97(t, Jc,d ¼ 7.4 Hz, 3H, d-HR) ppm. 13C NMR (100 MHz, D2O)
7.0 Hz, 1H, a-HR), 2.09–2.02 (4s, 12H, COCH3 overlapping with data for R isomer: d ¼ 88.2 (C-1R), 80.3 (C-5R), 77.0 (C-3R), 68.7
COCH3 of 4dS) ppm. 13C NMR (100 MHz, CDCl3) data for R (C-4R), 67.8 (C-2R), 60.5 (C-6R), 45.7 (C-aR), 24.1 (C-bR over-
isomer: d ¼ 170.5–168.8 (COCH3 overlapping with COCH3 of lapping with C-bS), 21.3 (C-cR), 12.9 (C-dR) ppm HRMS (ESI):
4dS), 125.6 (C-bR), 124.3 (C-cR), 85.5 (C-1R), 77.0 (C-5R), 73.3 (C- calcd for C10H20NaO6S 291.0873 [M + Na]+; found 291.0879.
3R), 68.1 (C-4R), 66.7 (C-2R), 62.3 (C-6R), 51.8 (C-aR), 20.8–20.6
(COCH3 overlapping with COCH3 of 4dS) ppm. HRMS (ESI): oxidation reaction of the free thiosaccharide 3i afforded the
calcd for C17H24NaO10S 443.0982 [M + Na]+; found 443.0980.
diastereomeric mixture of sulfoxides 4iR,S aer purication by
Benzyl 1-thio-b-D-glucopyranoside (R,S)-S-oxide (4iR,S). The
Methyl 1-thio-b-D-glucopyranoside (R,S)–S-oxide (4gR,S). The column chromatography. The mixture (18.4 mg, 53%, ratio S/R,
oxidation reaction of the free thiosaccharide 3g gave the diaste- 1 : 1) was obtained as a white solid and showed a single spot by
reomeric mixture of sulfoxides 4gR,S that could not be separated TLC analysis. Rf ¼ 0.56, CH2Cl2/MeOH (4 : 1). 1H NMR (400
by column chromatography. The mixture (19.9 mg, 88%, ratio S/R, MHz, D2O) data for S isomer: d ¼ 7.53–7.46 (m, 5H, aromaticS
1.5 : 1) was obtained as a white solid and showed a single spot by overlapping with aromaticR of 4iR), 4.58 (d, J1,2 ¼ 9.7 Hz, 1H, 1-
1
TLC analysis. Rf ¼ 0.38, MeCN/H2O (4 : 1). H NMR (400 MHz, HS), 4.48 (d, Jgem ¼ 13.2 Hz, 1H, a-HS), 4.41 (d, Jgem ¼ 13.1 Hz,
D2O) data for S isomer: d ¼ 4.63 (d, J1,2 ¼ 9.7 Hz, 1H, 1-HS), 4.00 1H, a-HS), 4.00 (dd, J6a,6b ¼ 12.6, J5,6a ¼ 2.0 Hz, 1H, 6a-HS), 3.84
(dd, J6a,6b ¼ 12.6, J5,6a ¼ 2.1 Hz, 1H, 6a-HS), 3.83 (dd, J6a,6b ¼ 12.6, (dd, J6a,6b ¼ 12.6, J5,6b ¼ 5.8 Hz, 1H, 6b-HS), 3.66–3.45 (m, 4H, 2-
J5,6b ¼ 5.9 Hz, 1H, 6b-HS), 3.71–3.61 (m, 3H, 3-HS, 2-HS, 5-HS HS, 3-HS, 5-HS, 4-HS overlapping with 3-HR, 5-HR, 4-HR of
overlapping with 3-HR, 5-HR of 4gR), 3.50 (t, J3,4 ¼ J4,5 ¼ 9.3 Hz, 4iR) ppm. 13C NMR (100 MHz, D2O) data for S isomer: d ¼
1H, 4-HS), 2.85 (s, 3H, CH3SOS) ppm. 13C NMR (100 MHz, D2O) 130.6–128.9 (aromaticS overlapping with aromaticR of 4iR), 90.8
data for S isomer: d ¼ 91.0 (C-1S), 80.8 (C-5S), 77.2 (C-3S), 69.4 (C- (C-1S), 80.9 (C-5S), 77.2 (C-3S), 69.4 (C-2S), 68.9 (C-4S), 60.8 (C-6S),
2S), 69.0 (C-4S), 60.9 (C-6S), 30.7 (CH3SOS) ppm. 1H NMR (400 51.7 (C-aS) ppm. 1H NMR (400 MHz, D2O) data for R isomer: d ¼
MHz, D2O) data for R isomer: d ¼ 4.25 (d, J1,2 ¼ 9.6 Hz, 1H, 1-HR), 7.53–7.46 (m, 5H, aromaticR overlapping with aromatics of 4iS),
4.03 (dd, J6a,6b ¼ 12.7, J5,6a ¼ 2.2 Hz, 1H, 6a-HR), 3.88 (dd, J6a,6b
¼
4.53 (d, Jgem ¼ 12.6 Hz, 1H, a-HR), 4.42 (d, Jgem ¼ 12.5 Hz, 1H, a-
12.6, J5,6b ¼ 4.9 Hz, 1H, 6b-HR), 3.74 (dd, J1,2 ¼ 9.5, J2,3 ¼ 9.2 Hz, HR), 4.07 (d, J1,2 ¼ 10.0 Hz, 1H, 1-HR), 4.07 (dd, J6a,6b ¼ 12.6, J5,6a
1H, 2-HR), 3.71–3.61 (m, 2H, 3-HR, 5-HR overlapping with 3-HS, 2- ¼ 2.0 Hz, 1H, 6a-HR), 3.90 (dd, J6a,6b ¼ 12.7, J5,6b ¼ 4.8 Hz, 1H,
HS, 5-HS of 4gS), 3.55 (t, J3,4 ¼ J4,5 ¼ 9.2 Hz, 1H, 4-HR), 2.86 (s, 3H, 6b-HR), 3.76 (dd, J1,2 ¼ 9.9, J2,3 ¼ 8.7 Hz, 1H, 2-HR), 3.66–3.45 (m,
CH3SOR) ppm. 13C NMR (100 MHz, D2O) data for R isomer: d ¼ 3H, 3-HR, 5-HR, 4-HR overlapping with 2-HS, 3-HS, 5-HS, 4-HS of
89.3 (C-1R), 80.3 (C-5R), 77.0 (C-3R), 68.9 (C-4R), 68.0 (C-2R), 60.6 (C- 4iS) ppm. 13C NMR (100 MHz, D2O) data for R isomer: d ¼
6R), 31.7 (CH3SOR) ppm. HRMS (ESI): calcd for C7H14NaO6S 130.6–128.9 (aromaticR overlapping with aromaticS of 4iS), 86.8
249.0403 [M + Na]+; found 249.0395.
(C-1R), 80.4 (C-5R), 76.9 (C-3R), 68.7 (C-4R), 67.6 (C-2R), 60.6 (C-
Butyl 1-thio-b-D-glucopyranoside (R,S)-S-oxide (4hR,S). The 6R), 51.6 (C-aR) ppm. HRMS (ESI): calcd for C13H18NaO6S
oxidation reaction of the free thiosaccharide 3h afforded aer 325.0716 [M + Na]+; found 325.0720.
purication by column chromatography the diastereomeric
mixture of sulfoxides 4hR,S. The mixture (19.1 mg, 66%, ratio S/
Conclusions
R, 1.6 : 1) was obtained as a colorless syrup and showed a single
1
spot by TLC analysis. Rf ¼ 0.58, CH2Cl2/MeOH (4 : 1). H NMR Photooxidation reactions of thiomonosaccharides under
(400 MHz, D2O) data for S isomer: d ¼ 4.62 (d, J1,2 ¼ 9.7 Hz, 1H, aerobic conditions were performed employing different organic
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dyes as sensitizers. Among the photocatalysts evaluated tetra-O-
acetyl riboavin provided good to excellent yields for the
oxidation of alkyl, benzyl, and vinyl thioglycosides in consid-
erably short reaction times. In addition, outstanding chemo-
selectivity towards the glycosyl sulfoxides without over-
oxidation to sulfone was achieved. Furthermore, high selec-
tivity was observed for the photooxidation of alkyl, allyl and
benzyl thioglycosides as, under the same controlled conditions,
phenyl thioglycosides are not oxidized. In the photooxidation
reactions the formation of the sulfoxides with the SS congu-
ration was favored in almost all cases, due to the stereo-
selectivity generated by the asymmetric induction of the
glucosyl residue.
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20 J. P. Colomer, B. Fernandez de Toro, F. J. Canada,
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There are no conicts to declare.
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para la investigacion Cientıca y Tecnologica Argentina (FON- 24 E. G. Mata, Phosphorus, Sulfur Silicon Relat. Elem., 1996, 117,
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receipt of a fellowship from CONICET. J. P. C., A. B. P. and O. V. 25 Sigma-Aldrich,
are research members from CONICET. The authors want to product/aldrich/273031, 2020.
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27 V. Latour, T. Pigot, M. Simon, H. Cardy and S. Lacombe,
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