Stereoselective synthesis of β-glycosyl thiols and their synthetic applications

Article abstract of DOI:10.1021/jo302115k

A significantly fast reaction condition for the exclusive preparation β-glycosyl thiol derivatives has been developed successfully. The reaction condition is one-step, fast, high yielding, highly stereoselective, and requires only benchtop chemicals. Further reaction of glycosyl thiol derivatives with Michael acceptors and alkylating agents furnished thioglycosides and (1,1)-thiolinked trehalose analogs.

Full text of DOI:10.1021/jo302115k

Note
pubs.acs.org/joc
Stereoselective Synthesis of β‑Glycosyl Thiols and Their Synthetic
Applications
Manas Jana and Anup Kumar Misra*
Bose Institute, Division of Molecular Medicine, P-1/12, C.I.T. Scheme VII M, Kolkata 700054, India
S
* Supporting Information
ABSTRACT: A significantly fast reaction condition for the
exclusive preparation β-glycosyl thiol derivatives has been
developed successfully. The reaction condition is one-step, fast,
high yielding, highly stereoselective, and requires only benchtop
chemicals. Further reaction of glycosyl thiol derivatives with
Michael acceptors and alkylating agents furnished thioglycosides and (1,1)-thiolinked trehalose analogs.
lycosyl thiol derivatives or 1-thiosugar derivatives are
important building blocks for the synthesis of various
include longer reaction time, multiple steps, unsatisfactory
G
yield, formation isomeric mixture, use of expensive reagent
[e.g., (TMS)2S], use of hazardous gas (e.g., H2S), use of
appropriately functionalized substrates, etc. Hence, there is a
strong need for the stereoselective preparation of glycosyl thiol
derivatives. In this context, we envisioned that SN2 substitution
of the bromide ion of glycosyl bromide with sodium
carbonotrithioate, a H2S equivalent, derived from the reaction
of sodium sulfide with carbon disulfide could furnish the
desired glycosyl thiol derivatives with high stereoselectivity in
one-step reaction condition. In this communication, a one-step
synthesis of exclusively β-glycosyl thiol derivatives, together
with their applications in the Michael reaction with conjugated
alkenes and preparation of thioglycosides, is presented.
Initially, carbon disulfide (CS2) was added to sodium sulfide
(Na2S·9H2O) in equimolar ratio in DMF to generate a red
solution of sodium carbonotrithioate. On addition of the
acetobromo-α-D-glucose (1; 1.0 equiv) to the in situ generated
sodium carbonotrithioate solution at room temperature, the red
color of the solution immediately turned into yellow. Aqueous
workup of the reaction mixture furnished 2,3,4,6-tetra-O-acetyl-
1-thio-β-D-glucopyranose (15) exclusively in a 80% yield. Other
commonly used solvents (e.g., CH2Cl2, CHCl3, THF, toluene,
CH3CN, DMSO, Et2O, CH3OH, H2O, etc.) have been
screened and did not produce satisfactory results (Table 1).
Although the yield of the product formation in DMSO and
DMF were comparable, DMF has been chosen as the reaction
solvent because of the shortcomings associated with DMSO
(e.g., high boiling point, unpleasant odor, chance of unwanted
byproduct formation, etc.). Use of alcohol or water did not
furnish satisfactory yields, and degraded starting materials were
obtained as the major products. To optimize the reaction
condition, a series of experiments were carried out using
Na2S·9H2O (2.0 equiv) and 0.5−1.5 equiv of CS2 in DMF at
room temperature. It was observed that the yield of the
formation of compound 15 can be raised to 90% by the
thiooligosaccharides and glycoconjugate derivatives.1−3 Because
of the exceptional stability of the sulfide linkages toward the
enzymatic hydrolysis,4 thiolinked glycoconjugates are consid-
ered as promising molecules to design therapeutics.5 The
anomeric configuration of the glycosyl thiol derivatives mostly
remains unaffected6,7 during the course of synthetic trans-
formations in contrast to its normal sugar hemiacetal
derivatives. Glycosyl thiols are being used in the preparation
of a series of carbohydrate intermediates useful in the synthesis
of biologically important molecules such as C-glycosides,8
glycosyl sulfenamide/sulfonamide derivatives,9,10 glycosyl di-
sulfide derivatives,11 glycosyl thionolactone derivatives, etc.
They can also be transformed into new class of glycosyl donors
such as glycosyl N-phenyltrifluorothioacetimidate13 and glyco-
syl sulfenic acid14 derivatives in the glycosylations. In the recent
past, glycosyl thiols were used in the synthesis of sulfur-
containing glycolipids,15 glycopeptides, and glycoproteins16 as
well as in the radical mediated coupling with alkenes.17
The conventional approaches for the synthesis of glycosyl
thiol derivatives include a two-step reaction sequence involving
the SN2 substitution reaction of glycosyl halide or acetate with
thiourea18,19 or thioacetate20 and hydrolysis or de-S-acetylation
of the resulting intermediate. Reductive removal of the benzyl
group from the anomeric thiobenzyl glycoside21 has also been
explored for the preparation of glycosyl thiol derivatives.
Another method for the preparation of glycosyl thiol derivatives
involves bubbling of hydrogen sulfide gas through the solution
of glycosyl halides in hydrogen fluoride.22 Davis et al.23
reported the direct preparation of glycosyl thiol derivatives on
treatment of the glycosyl hemiacetal derivatives with Law-
esson’s reagent in moderate yields with no stereoselectivity.
Zhu et al.24,25 and Schmidt et al.26 reported the exclusive
preparation of α-glycosyl thiol derivatives by the treatment of
1,6-anhydro sugar derivative and glycosyl trichloroacetimidate
derivatives with bis(trimethylsilyl)sulfide [(TMS)2S] respec-
tively. Although a number of reports appeared in the literature
for the preparation of glycosyl thiol derivatives, most of the
reaction conditions suffer from several shortcomings, which
Received: October 1, 2012
© XXXX American Chemical Society
A
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Note
25) were prepared in excellent yield (Table 3). The reaction is
equally effective in D- and L-sugar derivatives as well as in
disaccharide derivatives. Although most of the glycosyl
bromides furnished corresponding glycosyl thiol derivatives,
treatment of 3,4,6-tri-O-acetyl-2-azido-2-deoxy-α-D-glucopyra-
nosyl bromide (12) with CS2 and Na2S·9H2O resulted in the
exclusive formation of 3,4,6-tri-O-acetyl-D-glucal (26) in a 94%
yield. This unexpected outcome may be explained either by
considering the elimination of sodium bromide followed by
elimination of hydrazoic acid (HN3) from compound 12 or
considering the instability of azido group in the presence of
sodium carbonotrithioate formed in situ and elimination of
HBr under the basic reaction condition. However, the exact
mechanism for the formation of compound 26 from compound
12 is yet to be established. In contrast to the formation of
compound 19 from compound 5, reaction of 2-acetamido-
3,4,6-tri-O-acetyl-2-deoxy-α-D-glucopyranosyl bromide (13)
with CS2 and Na2S·9H2O furnished only a mixture of oxazoline
derivative (13a) and hemiacetal derivative without formation of
the expected thiol derivative, presumably due to the faster rate
of intramolecular cyclization (oxazoline formation) and
hydrolysis than SN2 substitution. A scaled up preparation (10
g) of glycosyl thiol derivative 15 was achieved with similar yield
as in the small-scale preparation. Commonly used hydroxyl
protecting groups (e.g., acetyl, benzoyl, benzyl, N-phthalimido
etc.) remained unaffected under the reaction condition. The
stereochemistry of the anomeric center of the glycosyl thiol
derivatives were determined from the coupling constant (J1,2)
of the H-1 as well as SH (J H‑1,SH = 8−10 Hz for β-glycosyl thiol
and J H‑1,SH = 4−5 Hz for α-glycosyl thiol). Another noteworthy
point is that β-D-mannosidic thiol and β-L-rhamnosidic thiol
derivatives can be achieved exclusively under the reaction
condition, avoiding the formation of anomerized or oxidized
products. In case of D-mannose and L-rhamnose derived
glycosyl thiol derivatives, the anomeric configurations were
Table 1. Screening of Solvents Appropriate for the Reaction
Sl. no.
solvent
time (min)
yield (%)
a
b
1
2
CH2Cl2
60
60
60
60
90
90
5
10
a
b
CHCl3
15
a
3
THF
a
b
4
CH3CN
25
c
5
toluene
c
6
Et2O
7
DMSO
DMF
85
90
8
5
b
9
CH3OH
H2O
60
60
20
b
10
10
a
b
Na2S·9H2O partly soluble. Most of the starting material degraded.
c
Na2S·9H2O insoluble.
reaction of compound 1 with a premixed mixture of CS2 (1.5
equiv) and Na2S·9H2O (2.0 equiv) in DMF at room
temperature in 5 min (Scheme 1) (Table 2). Use of less
Scheme 1. Reaction of Glycosyl Bromides with Carbon
Disulfide and Sodium Sulfide to Furnish β-Glycosyl Thiols
amount of CS2 (0.5 equiv) resulted in the significant formation
of symmetrical bis-glycosyl sulfide derivative (15a), may be due
to the condensation of unreacted glycosyl bromide with the in
situ generated glycosyl thiol (15). In a control experiment,
compound 1 was treated with Na2S·9H2O (2.0 equiv) in DMF
at room temperature without addition of CS2. The reaction did
not proceed even after 12 h and only degraded starting material
was obtained (Table 2). The exclusive formation of glycosyl
thiol (15) using 2.0 equiv of CS2 and bis-glycosyl disulfide
(15a) using 0.5 equiv of CS2 confirmed that use of excess CS2
increased the rate of the glycosyl thiol formation, minimizing
the chances of the reaction of glycosyl thiol with unreacted
glycosyl bromide in the reaction mixture as well as hydrolysis of
glycosyl bromide. In earlier reports,27 reaction of glycosyl
bromide with Na2S·9H2O in a phase transfer reaction at high
temperature furnished bis-glycosyl sulfide derivatives instead of
giving glycosyl thiol derivative. Following the optimized
reaction condition, a series of glycosyl thiol derivatives (15−
1
determined using JSH−H1 in the H spectra and JC‑1,H‑1 values
from the 1H coupled 13C NMR spectra.28 Appearance of JC‑1,H‑1
values 141.2 and 141.4 Hz in the 1H coupled 13C NMR spectra
of compounds 17 and 20, respectively, confirmed the β-
configuration of the thiol derivatives (JC‑1,H‑1 less than 160
Hz).28 The exclusive formation of β-glycosyl thiol derivatives
could be explained by considering the SN2 displacement of the
bromide ion by the carbonotrithioate ion derived from the
reaction of CS2 and Na2S·9H2O, followed by elimination of CS2
in situ. Because all glycosyl bromides used in this study have α-
configuration, β-glycosyl thiol was formed as the exclusive
products. It is worth mentioning that the reaction condition is
significantly fast and the exclusive formation of β-glycosyl thiols
was observed from α-glycosyl bromides (Scheme 2). The
Table 2. Optimization of the Quantity of CS2 for the Preparation Glycosyl Thiol Derivative
product (%)
Sl. no.
CS2 (equiv)
Na2S·9H2O(equiv)
time (min)
15
15a
1
2
3
4
0.5
1.0
1.5
2.0
2.0
2.0
2.0
5
5
60
30
50
90
5
720
B
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Note
Scheme 2. Plausible Mechanism for the Stereoselective
Formation of Glycosyl Thiol Derivatives
Scheme 3. Reaction of β-Glycosylthiol Derivatives with
Conjugated Alkene Derivatives
anomeric configuration of the glycosyl thiols was not influenced
by the functional group (neighboring group participating or
nonparticipating) present at C-2 position of the sugar
backbone, which was established by the formation of exclusive
β-thiol derivative (25) from the per-O-benzylated-α-D-gluco-
pyranosyl bromide (11) (entry 11, Table 3). Contrary to the
earlier report,27 formation of oxidized product such as bis-
glycosyl sulfide or glycosyl disulfide was not observed during
the reaction. The glycosyl thiol derivatives were quite stable and
have been used successfully for the preparation of unsym-
metrical sulfide derivatives.
Application of the glycosyl thiol derivatives in the Michael
addition was explored to prepare thio-linked glycoconjugate
derivatives. Treatment of a series of glycosyl thiol derivatives
with α,β-unsaturated ester or ketone in methanol at room
temperature furnished excellent yield of Michael addition
products without requirement of any catalyst (Scheme 3, Table
4). Reaction of glycosyl thiols with methyl propiolate (27)
furnished exclusively E-isomer of the Michael addition products
(entries 1, 2; compounds 29, 30; Table 4), whereas reactions of
glycosyl thiols with 2-cyclohexenone (28) furnished mixture of
diastereomeric products (entries 3, 4; compounds 31, 32; Table
4), which were confirmed from the NMR spectral analysis. This
methodology has the potential to find application in the
conjugation of carbohydrate derivatives to protein/peptide17,29
through a spacer linker or to immobilize glycans to solid
support.30
thioglycoside derivatives (Scheme 4) (entries 1−4, Compounds
33−36, Table 5). Yields were excellent in all reactions, and
formation of anomerization products of the thioglycosides was
not observed. Similarly, reaction of β-glycosyl thiol derivatives
with a diastereomeric mixture of lactic acid ester triflate salt
furnished thio-linked β-thioglycosyl lactate derivatives in
excellent yields as a diastereomeric mixtures and the
diastereomeric ratios (dr) were confirmed from the integration
values of the anomeric protons and methyl group of the lactate
1
moiety in the H NMR spectra (Scheme 4) (entries 5, 6;
compounds 37, 38; Table 5). It is worth noting that exclusive
formation of β-D-mannopyranosyl thiolactate derivative (38)
(appearance of JC‑1,H‑1 = 155.0 Hz in the 1H coupled 13C NMR
spectrum)28 was achieved using the present reaction condition
which is difficult to obtain using other methodologies. Further
treatment of β-glycosyl thiol derivative with α-glycosyl bromide
derivatives in DMF in the presence of triethylamine furnished
unsymmetrical 1,1-thio-linked di- and trisaccharide derivatives
(trehalose analogues) in excellent yield (Scheme 4) (com-
pounds 39, 40; Table 5). The structural characterization of all
synthesized products was carried out using NMR spectral data.
In summary, an expedient one-step reaction condition for the
synthesis of exclusive β-glycosyl thiol derivatives has been
developed by treating glycosyl bromide derivatives with a
mixture of CS2 and Na2S·9H2O at room temperature. The
reaction is significantly fast and high yielding with high
stereoselectivity. The β-glycosyl thiol derivatives were reacted
with alkyl halides and triflate derivative to furnish β-thioglyco-
In another approach, β-glycosyl thiol derivatives were
allowed to react with a variety of alkyl halides in the presence
of catalytic amount of triethylamine in DMF to furnish alkyl β-
Table 3. Stereoselective synthesis of β-Glycosyl Thiol Derivatives in DMF
a
b
c
d
Yield of isolated product. α/β ratio of the crude reaction mixture. Yield in parentheses is 10 g scale. Exclusive formation of 3,4,6-tri-O-acetyl-D-
e
glucal (26) (94%) in 5 min. Formation of a mixture of oxazoline derivative (13a) and hemiacetal derivative in 10 min.
C
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Note
Table 4. Michael Addition of β-Glycosyl Thiols with Activated Alkenes
became yellow and the reaction mixture was stirred at room
temperature for an appropriate time as mentioned in Table 1. The
reaction mixture was diluted with water and extracted with EtOAc (50
mL), dried (Na2SO4), and concentrated to furnish the crude product,
which was purified over SiO2 using hexane−EtOAc as eluant.
Analytical data for the new compounds are as follows:
Scheme 4. Reaction of β-Glycosyl Thiols with Alkyl Halide,
Triflate and Glycosyl Halide Derivatives
Compound 24. Yield 590 mg (90%); eluant, hexane−EtOAc (4:1);
25
white solid; mp 204−205 °C (Et2O−hexane); [α]D +150 (c 1.0,
CHCl3). IR (KBr): 2568, 1753, 1374, 1225, 1165, 1051, 915 cm−1. 1H
NMR (500 MHz, CDCl3): δ 5.35 (d, J = 2.0 Hz, 1 H, H-4B), 5.25 (dd,
J = 11.0,3.0 Hz, 1 H, H-3B), 5.14 (d, J = 3.0 Hz, 1 H, H-1B), 5.08 (t, J =
9.5 Hz each, 1 H, H-2A), 5.00 (t, J = 10.0 Hz each, 1 H, H-4A), 4.98
(dd, J = 10.5, 3.0 Hz, 1 H, H-2B), 4.81 (t, J = 9.5 Hz each, 1 H, H-3A),
4.42 (t, J = 10.0 Hz each, 1 H, H-1A), 4.18−4.16 (m, 1 H, H-5B),
4.01−3.98 (m, 2 H, H-6abB), 3.64−3.55 (m, 3 H, H-5A, H-6abA), 2.19
(d, J = 10.0 Hz, 1 H, SH), 2.07, 2.06, 2.02, 2.00, 1.96, 1.94, 1.92 (7 s,
21 H, 7 COCH3). 13C NMR (125 MHz, CDCl3): δ 170.3, 170.1,
170.0, 169.9, 169.7, 169.4, 169.1 (7 COCH3), 96.1 (C-1B), 78.5 (C-
1A), 77.1 (C-5A), 73.6 (2 C, C-3A, C-4A), 68.6 (C-2A), 68.2.(C-2B),
67.9 (C-4B), 67.4 (C-3B), 66.3 (C-5B), 65.9 (C-6A), 61.4 (C-6B), 20.9,
20.7, 20.6 (2 C), 20.5 (3 C) (7 COCH3). ESI-MS: 675.1 [M + Na]+.
Anal. Calcd for C26H36O17S (652.16): C, 47.85; H, 5.56. Found: C,
47.70; H, 5.75.
side derivatives. The reaction has been further extended toward
the preparation of (1,1)-thiolinked di- and trisaccharide
derivatives. Present methodology will be considered as an
attractive alternative in this area because of the above-
mentioned advantages over the existing methodologies for
the synthesis of β-glycosyl thiol derivatives and their use in the
preparation of thiolinked glycomimetics.
EXPERIMENTAL SECTION
■
General Comments. All reactions were monitored by thin layer
chromatography over silica gel coated TLC plates. The spots on TLC
were visualized by warming ceric sulfate (2% Ce(SO4)2 in 2N H2SO4)
sprayed plates in hot plate. Silica gel 230−400 mesh was used for
column chromatography. 1H and 13C NMR and 2D COSY and HSQC
spectra were recorded on a 500 NMR spectrometer (500 MHz for 1H,
125 MHz for 13C) using CDCl3 as solvent and TMS as internal
reference unless stated otherwise. Chemical shift value is expressed in
δ ppm. ESI-MS were recorded on a Micromass mass spectrometer.
Commercially available grades of organic solvents of adequate purity
are used in all reactions.
Compound 25. Yield 456 mg (82%); eluant, hexane−EtOAc (7:1);
25
white solid; mp 60−62 °C (Et2O−hexane); [α]D +57 (c 1.0,
CHCl3). IR (KBr): 2556, 1756, 1372, 1222, 1145, 915 cm−1. 1H NMR
(500 MHz, CDCl3): δ 7.37−7.13 (m, 20 H, Ar−H), 4.97−4.53 (m, 8
H, 4 PhCH2), 4.50 (t, J = 9.0 and 8.0 Hz, 1 H, H-1), 3.74−3.68 (m, 2
H, H-3, H-4), 3.67−3.63 (m, 2 H, H-6ab), 3.48−3.46 (m, 1 H, H-5),
3.73 (t, J = 9.0 Hz each, 1 H, H-2), 2.29 (d, J = 8.0 Hz, 1 H, SH). 13C
NMR (125 MHz, CDCl3): δ 138.8−127.6 (Ar−C), 86.5 (C-1), 84.8
(C-5), 79.8 (C-3), 79.5 (C-4), 77.7 (C-2), 75.7 (2 C, 2 PhCH2), 75.0
(PhCH2), 73.5 (PhCH2), 68.7 (C-6). ESI-MS: 579.2 [M + Na]+. Anal.
Calcd for C34H36O5S (556.22): C, 73.35; H, 6.52. Found: C, 73.18; H,
6.75.
General Experimental Condition for the Preparation of β-
Glycosyl Thiol Derivatives. To a solution of sodium sulfide (2.0
mmol) in DMF (5 mL) was dropwise added carbon disulfide (1.5
mmol) at room temperature. On addition of the glycosyl bromide (1.0
mmol) to the resulting red-colored solution, the color of the reaction
General Experimental Condition for the Michael Addition of
Glycosyl Thiol Derivatives with Activated Alkenes. A mixture of
Table 5. Reaction of β-Glycosyl Thiols with Alkyl Halides, Triflate, and Glycosyl Bromide
Sl.
time
(min)
yield
(%)
no. thiol
alkylating agent
thioglycoside
1
2
3
4
5
15 allyl bromide
allyl 2,3,4,6-tetra-O-acetyl-1-thio-β-D-glucopyranoside (33)37
benzyl 2,3,4,6-tetra-O-acetyl-1-thio-β-D-galactopyranoside (34)37
methallyl 2,3,4-tri-O-acetyl-1-thio-β-L-fucopyranoside (35)
benzyl per-O-acetyl-1-thio-β-D-lactopyranoside (36)38
30
30
30
30
5
94
90
90
90
90
16 benzyl bromide
21 β-methallyl chloride
22 benzyl bromide
a
15 CH3CH(OTf)
benzyl-2-methyl-propanoyl 2,3,4,6-tetra-O-acetyl-1-thio-β-D-glucopyranoside (37)
COOBn
a
6
17 CH3CH(OTf)
benzyl-2-methyl-propanoyl 2,3,4,6-tetra-O-acetyl-1-thio-β-D-mannopyranoside (38)
5
88
COOBn
7
8
21
23
1
1
(2,3,4-tri-O-acetyl-β-L-fucopyranosyl)-(1→1)-2,3,4,6-tetra-O-acetyl-1-thio-β-D-glucopyranoside (39)
180
200
86
84
(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)-(1→1)-2,3,4,2′,3′,4,6′-hepta-O-acetyl-1-thio-β-D-
maltopyranoside (40)
a
dr: 1.4:1.
D
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Note
glycosyl thiol derivative (1.0 mmol) and conjugated alkene derivative
(1.1 mmol) in methanol was allowed to stir at room temperature for
appropriate time as mentioned in the Table 2. After formation of thio-
adduct (monitored by TLC), the reaction mixture was concentrated
under reduced pressure to give the crude product, which was purified
over SiO2 using hexane−EtOAc as eluant. Analytical data for the new
compounds are as follows:
solution of glycosyl thiol derivative (1.0 mmol) in DMF (5 mL) were
added alkylating agent/glycosyl halide (1.1 mmol) and Et3N (2
drops), and reaction mixture was allowed to stir at room temperature
for appropriate time as mentioned in Table 3. The reaction mixture
was diluted with water and extracted with CH2Cl2 (50 mL). The
organic layer was washed with water, dried (Na2SO4) and
concentrated to give the crude product which was purified over
SiO2 using hexane−EtOAc as eluant. Analytical data for the new
compounds are as follows:
Compound 29. Yield 600 mg (88%); eluant, hexane−EtOAc (6:1);
25
white solid; mp 142−144 °C (Et2O−hexane); [α]D −2 (c 1.0,
CHCl3). IR (KBr): 2925, 1732, 1601, 1583, 1451, 1315, 1268, 1175,
Compound 35. Yield 318 mg (90%); eluant, hexane−EtOAc (4:1);
1
25
1088, 1068, 1026, 802, 708, 685 cm−1. H NMR (500 MHz, CDCl3):
yellow oil; [α]D +111 (c 1.0, CHCl3). IR (neat): 2926, 2854, 1750,
1
δ 7.72−7.18 (m, 21 H, Ar−H, HC−CO), 5.89 (d, J = 10.0 Hz, 1 H,
S−CH), 5.85 (t, J = 9.5 Hz each, 1 H, H-2), 5.64 (t, J = 10.0 Hz
each, 1 H, H-3), 5.61 (t, J = 10.0 Hz each, 1 H, H-4), 4.90 (d, J = 9.5
Hz, 1 H, H-1), 4.58 (dd, J = 12.0, 2.0 Hz, 1 H, H-6a), 4.41 (dd, J =
12.0, 5.0 Hz, 1 H, H-6b), 4.18−4.16 (m, 1 H, H-5), 3.63 (s, 3 H,
OCH3). 13C NMR (125 MHz, CDCl3): δ 166.5 (COOCH3), 165.9,
165.6, 165.0, 164.7 (4 PhCO), 142.6 (SCH), 133.4−128.3 (Ar-C),
115.1 (CHCO), 83.3 (C-1), 76.9 (C-5), 73.9 (C-2), 70.6 (C-3),
69.3 (C-4), 63.0 (C-6), 51.4 (COOCH3). ESI-MS: 719.1 [M + Na]+.
Anal. Calcd for C38H32O11S (696.16): C, 65.51; H, 4.63. Found: C,
65.35; H, 4.80.
1437, 1370, 1247, 1224, 1084, 1057, 918, 758 cm−1. H NMR (500
MHz, CDCl3): δ 5.24 (d, J = 3.5 Hz, 1 H, H-4), 5.20 (t, J = 10.0 Hz
each, 1 H, H-2), 5.01 (dd, J = 10.0, 3.0 Hz, 1 H, H-3), 4.88−4.85 (m, 2
H, CH2), 4.39 (d, J = 10.0 Hz, 1 H, H-1), 3.75−3.72 (m, 1 H, H-5),
3.42 (d, J = 13.0 Hz, 1 H, CH2), 3.14 (d, J = 13.0 Hz, 1 H, CH2), 2.17,
2.05, 1.98 (3 s, 9 H, 3 COCH3), 1.81 (s, 3 H, CH3), 1.21 (d, J = 6.0
Hz, 3 H, CCH3). 13C NMR (125 MHz, CDCl3): δ 170.4, 169.9, 169.4
(3 COCH3), 140.5 (CH2−C(CH3)), 114.3 (CH2), 82.0 (C-1),
73.0 (C-3), 72.4 (C-4), 70.4 (C-2), 67.2 (C-5), 37.3 (CH2), 20.8, 20.7,
20.6 (2 C) (3 COCH3, CH3), 16.3 (CCH3). ESI-MS: 383.1 [M +
Na]+. Anal. Calcd for C16H24O7S (360.12): C, 53.32; H, 6.71. Found:
C, 53.15; H, 6.86.
Compound 30. Yield 340 mg (90%); eluant, hexane−EtOAc (5:1);
25
yellow oil; [α]D +92 (c 1.0, CHCl3). IR (neat): 2986, 1747, 1704,
Compound 37. (dr 1.4:1) 390 mg (90%); eluant, hexane−EtOAc
1
1586, 1437, 1372, 1222, 1170, 1055, 981, 933, 758, 707 cm−1. H
(3:1); yellow oil. IR (neat) (diastereomers 1 and 2): 2996, 2944, 1757,
1
NMR (500 MHz, CDCl3): δ 7.20 (d, J = 10.5 Hz, 1 H, CHCO),
5.87 (d, J = 10.0 Hz, 1 H, SCH), 5.45 (d, J = 3.0 Hz, 1 H, H-2), 4.99
(t, J = 10.0 Hz each, 1 H, H-4), 4.93 (dd, J = 10.0, 3.5 Hz, 1 H, H-3),
4.74 (br s, 1 H, H-1), 3.65 (s, 3 H, COOCH3), 3.55−3.52 (m, 1 H, H-
5), 2.10, 1.98, 1.90 (3 s, 9 H, 3COCH3), 1.21 (d, J = 6.0 Hz, 3 H,
CCH3). 13C NMR (125 MHz, CDCl3): δ 169.9, 169.7, 169.5 (3
COCH3), 166.6 (COOCH3), 144.4 (SCH), 114.1 (CHCO), 82.1
(C-1), 75.6 (C-3), 71.7 (C-4), 70.0 (C-2), 69.9 (C-5), 51.4
(COOCH3), 20.7, 20.6, 20.5 (3 COCH3), 17.6 (CCH3). ESI-MS:
413.0 [M + Na]+. Anal. Calcd for C16H22O9S (390.09): C, 49.22; H,
5.68. Found: C, 49.08; H, 5.85.
1441, 1351, 1232, 1088, 1056, 916, 755 cm−1. H NMR (500 MHz,
CDCl3) (diastereomer 1): δ 7.38−7.25 (m, 5 H, Ar−H), 5.22 (d, J =
12.0 Hz, 1 H, PhCH2), 5.12 (d, J = 12.0 Hz, 1 H, PhCH2), 5.08 (t, J =
10.0 Hz each, 1 H, H-3), 5.02 (t, J = 10.0 Hz each, 1 H, H-2), 4.95 (t, J
= 10.0 Hz each, 1 H, H-4), 4.70 (d, J = 10.0 Hz, 1 H, H-1), 4.18−4.14
(m, 1 H, H-6a), 4.06−4.03 (m, 1 H, H-6b), 3.75−3.72 (m, 1 H, CH),
3.61−3.58 (m, 1 H, H-5), 2.05, 2.02, 2.00, 1.98, (4 s, 12 H, 4 COCH3),
1.53 (d, J = 6.0 Hz, 3 H, CH3). 13C NMR (125 MHz, CDCl3): δ 171.5
(COOBn), 170.4, 169.9, 169.4, 169.1 (4 COCH3), 128.7−128.1 (Ar−
C), 82.9 (C-1), 75.8 (C-2), 73.9 (C-3), 69.9 (C-4), 68.1 (C-5), 67.0
(PhCH2), 61.8 (C-6), 41.6 (CH), 20.7, 20.6 (2 C), 20.5 (4 COCH3),
1
Compound 31. (dr: 1:1) 600 mg (87%); eluant, hexane−EtOAc
18.1 (CH3). H NMR (500 MHz, CDCl3) (diastereomer 2): δ 7.38−
(6:1); white solid; mp 80−82 °C (Et2O−hexane). IR (KBr): 2952,
7.25 (m, 5 H, Ar−H), 5.16 (br s, 2 H, PhCH2), 5.09 (t, J = 10.0 Hz
each, 1 H, H-3), 5.04 (t, J = 10.0 Hz each, 1 H, H-2), 4.93 (t, J = 10.0
Hz each, 1 H, H-4), 4.65 (d, J = 10.0 Hz each, 1 H, H-1), 4.18−4.15
(m, 1 H, H-6a), 4.06−4.02 (m, 1 H, H-6b), 3.64−3.59 (m, 1 H, CH),
3.45−3.43 (m, 1 H, H-5), 2.05, 2.02, 2.00, 1.98 (4 s, 12 H, 4 COCH3),
1.47 (d, J = 6.0 Hz, 3 H, CH3). 13C NMR (125 MHz, CDCl3): δ 171.6
(COOBn), 170.4, 169.9, 169.4, 169.1 (4 COCH3), 128.7−128.1 (Ar−
C), 81.9 (C-1), 75.9 (C-2), 73.8 (C-3), 69.8 (C-4), 68.0 (C-5), 66.9
(PhCH2), 61.7 (C-6), 39.0 (CH), 20.7, 20.6 (2 C), 20.5 (4 COCH3),
16.6 (CH3). ESI-MS: 549.1 [M + Na]+. Anal. Calcd for C24H30O11S
(526.15): C, 54.74; H, 5.74. Found: C, 54.56; H, 5.90.
1
1729, 1601, 1451, 1315, 1271, 117, 1091, 1068, 1026, 708 cm−1. H
NMR (500 MHz, CDCl3) (diastereomeric mixture): δ 7.97−7.19 (m,
20 H, Ar−H), 5.85 (d, J = 9.5 Hz, 1 H, H-1), 5.56 (t, J = 10.0 Hz each,
1 H, H-2), 5.45 (t, J = 10.0 Hz each, 1 H, H-3), 4.87 (t, J = 10.0 Hz
each, 1 H, H-4), 4.60−4.43 (m, 2 H, H-6ab), 4.12−4.08 (m, 1 H, H-5),
3.28−3.23 (m, 1 H, CH), 2.70−2.65 (m, 1 H, CH2), 2.38−1.47 (m, 7
H, CH2). 13C NMR (125 MHz, CDCl3): δ 207.5 (CO), 165.2, 165.1,
165.08, 165.0 (PhCO), 133.4−128.3 (Ar−C), 83.4 (C-1), 76.5 (C-5),
73.9 (C-3), 70.5 (C-4), 69.5 (C-2), 63.2 (C-6), 48.8 (CH2), 42.7
(CH), 40.7 (CH2), 32.5 (CH2), 24.3 (CH2). ESI-MS: 731.2 [M +
Na]+. Anal. Calcd for C40H36O10S (708.20): C, 67.78; H, 5.12. Found:
C, 67.62; H, 5.30.
Compound 32. (dr: 1:1) 585 mg (85%); eluant, hexane−EtOAc
(4:1); yellow oil. IR (neat): 2955, 2926, 1747, 1714, 1455, 1372, 1229,
1044, 760, 602 cm−1. 1H NMR (500 MHz, CDCl3) (R- and S-
mixture): δ 5.40 (d, J = 4.0 Hz, 1 H, H-4B), 5.34 (t, J = 10.0 Hz, 1 H,
H-2B), 5.26 (t, J = 10.0 Hz, 1 H, H-2A), 5.04 (t, J = 10.0 Hz, 1 H, H-
3A), 4.84 (d, J = 9.0 Hz, 1 H, H-1A), 4.82 (dd, J = 10.0, 3.0 Hz, 1 H, H-
3B), 4.63 (d, J = 10.0 Hz, 1 H, H-1B), 4.50−4.45 (m, 1 H, H-5B), 4.25−
4.15 (m, 2 H, H-6abA), 4.07−3.99 (m, 2 H, H-6abB), 3.95 (t, J = 10.0
Hz, 1 H, H-4A), 3.69−3.65 (m, 1 H, H-5A), 3.32−3.22 (m, 1 H, CH),
2.80−2.70 (m, 1 H, CH2), 2.45−2.25 (m, 3 H, CH2), 2.15, 2.10, 2.07,
2.03, 2.02, 2.01, 2.00 (7 s, 21 H, 7 COCH3), 1.75−1.70 (m, 4 H, CH2).
13C NMR (125 MHz, CDCl3): δ 207.5 (CO), 170.4, 170.3, 170.2,
Compound 38. (dr: 1.4:1) 380 mg (88%); eluant, hexane−EtOAc
(3:1); yellow oil. IR (neat) (diastereomers 1 and 2): 2938, 2856, 1760,
1
1457, 1377, 1257, 1220, 1088, 1067, 917 cm−1. H NMR (500 MHz,
CDCl3) (diastereomer 1): δ 7.41−7.33 (m, 5 H, Ar−H), 5.30 (d, J =
3.5 Hz, 1 H, H-2), 5.26 (d, J = 12.0 Hz, 1 H, PhCH2), 5.17 (t, J = 10.0
Hz each, 1 H, H-4), 5.13 (d, J = 12.0 Hz, 1 H, PhCH2), 4.86 (dd, J =
10.0, 3.0 Hz, 1 H, H-3), 4.76 (br s, 1 H, H-1), 4.22−4.16 (m, 1 H, H-
6a), 4.09−4.04 (m, 1 H, H-6b), 3.70−3.66 (m, 1 H, CH), 3.43−3.40
(m, 1 H, H-5), 2.18, 2.05, 1.97 (3 s, 12 H, 4 COCH3), 1.46 (d, J = 6.0
Hz, 3 H, CCH3). 13C NMR (125 MHz, CDCl3): δ 171.6 (COOBn),
170.6, 169.9, 169.4, 169.1 (4 COCH3), 128.8−128.2 (Ar−C), 80.6 (C-
1), 76.5 (C-2), 71.7 (C-3), 69.9 (C-4), 67.1 (PhCH2), 65.6 (C-5), 62.4
(C-6), 39.4 (CH), 20.7, 20.6 (2 C), 20.5 (4 COCH3), 16.4 (CH3). 1H
NMR (500 MHz, CDCl3) (diastereomer 2): δ 7.41−7.33 (m, 5 H,
Ar−H), 5.35 (d, J = 3.5 Hz, 1 H, H-2), 5.18 (t, J = 10.0 Hz, 1 H, H-4),
5.16−5.13 (m, 2 H, PhCH2), 4.96 (dd, J = 10.0, 3.0 Hz, 1 H, H-3),
4.86 (br s, 1 H, H-1), 4.22−4.16 (m, 1 H, H-6a), 4.07−4.04 (m, 1 H,
H-6b), 3.62−3.56 (m, 2 H, CH, H-5), 2.17, 2.06, 2.05, 1.97 (4 s, 12 H,
4 COCH3), 1.56 (d, J = 6.0 Hz, 3 H, CH3). 13C NMR (125 MHz,
CDCl3): δ 171.6 (COOBn), 170.6, 169.9, 169.4, 169.1 (4 COCH3),
128.8−128.2 (Ar−C), 80.9 (C-1), 76.3 (C-2), 71.7 (C-3), 70.7 (C-4),
67.1 (PhCH2), 65.6 (C-5), 62.6 (C-6), 41.2 (CH), 20.7, 20.6 (2 C),
170.0, 169.7, 169.4, 169.3 (7 COCH3), 95.6 (C-1B), 82.9 (C-1A), 76.3
(C-5A), 76.2 (C-4A), 72.7 (C-3A), 70.9 (C-2B), 70.0 (C-3B), 69.3 (C-
5B), 68.6 (C-2A), 68.0 (C-4B), 63.0 (C-6B), 61.5 (C-6A), 49.1 (CH2),
43.1 (CH), 40.7 (CH2), 32.1 (CH2), 24.3 (CH2), 20.9 (2 C), 20.7 (2
C), 20.6 (3 C) (7 COCH3). ESI-MS: 771.2 [M + Na]+. Anal. Calcd for
C32H44O18S (748.22): C, 51.33; H, 5.92. Found: C, 51.18; H, 6.15
General Experimental Condition for the Preparation of
Thioglycoside and (1,1)-Thio Oligosaccharide Derivatives. To a
E
dx.doi.org/10.1021/jo302115k | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
20.5 (4 COCH3), 17.7 (CH3). ESI-MS: 549.1 [M + Na]+. Anal. Calcd
for C24H30O11S (526.15): C, 54.74; H, 5.74. Found: C, 54.55; H, 5.90.
Compound 39. Yield 535 mg (86%); eluant, hexane−EtOAc (4:1);
ASSOCIATED CONTENT
■
S
* Supporting Information
1H NMR and 13C NMR spectra of compounds 15−26, 29−40,
13a, and 15a. This material is available free of charge via the
Internet at http://pubs.acs.org.
25
white solid; mp 140−142 °C (EtOH); [α]D +60 (c 1.0, CHCl3). IR
(KBr): 3469, 1752, 1371, 1227, 1042, 918 cm−1. 1H NMR (500 MHz,
CDCl3): δ 5.25 (d, J = 2.5 Hz, 1 H, H-4B), 5.22 (t, J = 10.0 Hz each, 1
H, H-2B), 5.19 (t, J = 9.5 Hz each, 1 H, H-2A), 5.09 (t, J = 10.0 Hz, 1
H, H-3A), 5.01 (t, J = 10.0 Hz each, 1 H, H-4A), 4.99 (dd, J = 10.0, 3.0
Hz, 1 H, H-3B), 4.74 (d, J = 10.0 Hz, 1 H, H-1B), 4.58 (d, J = 10.0 Hz,
1 H, H-1A), 4.26−4.21 (m, 1 H, H-6aA), 4.14−4.09 (m, 1 H, H-6bA),
3.87−3.82 (m, 1 H, H-5B), 3.74−3.71 (m, 1 H, H-5A), 2.17, 2.08, 2.07,
2.03, 2.01, 2.00, 1.99 (7 s, 21 H, 7 COCH3), 1.22 (d, J = 6.0 Hz, 3 H,
CCH3). 13C NMR (125 MHz, CDCl3): δ 171.0, 170.9, 170.8, 170.6,
170.3, 169.9, 169.8 (7 COCH3), 81.1 (C-1B), 81.0 (C-1A), 76.2 (C-
5A), 74.0 (C-5B), 73.7 (C-2A), 72.4 (C-3B), 70.4 (C-4B), 70.1 (C-2B),
68.0 (C-3A), 67.8 (C-4A), 62.2 (C-6A), 20.8, 20.7 (2 C), 20.6 (2 C),
20.5 (2 C) (7 COCH3), 16.3 (CCH3). ESI-MS: 659.1 [M + Na]+.
Anal. Calcd for C26H36O16S (636.17): C, 49.05; H, 5.70. Found: C,
48.88; H, 5.90.
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: akmisra69@gmail.com.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
M.J. thanks CSIR, New Delhi, for providing a Junior Research
Fellowship. This project was funded by Department of Science
and Technology (DST), New Delhi, India (project no. SR/S1/
OC-83/2010).
Compound 40. Yield 760 mg (84%); eluant, hexane−EtOAc (4:1);
25
white solid; mp 96−98 °C (EtOH); [α]D +53 (c 1.0, CHCl3). IR
1
(KBr): 2926, 2853, 1748, 1434, 1370, 1227, 1039, 759, 602 cm−1. H
NMR (500 MHz, CDCl3): δ 5.39 (d, J = 4.0 Hz, 1 H, H-1C), 5.31 (t, J
= 10.0 Hz each, 1 H, H-3C), 5.24 (t, J = 10.0 Hz each, 1 H, H-3B), 5.19
(t, J = 10.0 Hz each, 1 H, H-2B), 5.07 (t, J = 10.0 Hz each, 1 H, H-2A),
5.01 (2 t, J = 10.0 Hz each, 2 H, H-3A, H-4C), 4.85 (t, J = 10.0 Hz each,
1 H, H-4A), 4.83 (d, J = 10.0 Hz, 1 H, H-1B), 4.81 (dd, J = 10.0, 4.0
Hz, 1 H, H-2B), 4.77 (d, J = 10.0 Hz, 1 H, H-1A), 4.47−4.42 (m, 1 H,
H-6aA), 4.28−4.20 (m, H-6bA, H-6aB, H-aC), 4.14−4.10 (m, 1 H, H-
6bB), 4.05−4.01 (m, 1 H, H-6bc), 4.00 (t, J = 10.0 Hz each, 1 H, H-4B),
3.94−3.90 (m, 1 H, H-5C), 3.70−3.62 (m, 2 H, H-5A, H-5B), 2.16,
2.11, 2.09, 2.03, 2.02, 2.0, 1.99 (7 s, 33 H, 11 COCH3). 13C NMR (125
MHz, CDCl3): δ 170.4, 170.3, 170.2, 170.1, 170.0, 169.9, 169.8 (2 C),
169.7 (2 C), 169.6 (11 COCH3), 95.6 (C-1C), 80.7 (C-1B), 80.1 (C-
1A), 76.4 (2 C, C-5A, C-5B), 76.2 (C-3B), 73.8 (C-2B), 72.7 (C-4B),
71.0 (C-4A), 70.1 (C-2C), 69.9 (C-4C), 69.2 (C-3C), 68.6 (C-3A), 68.1
(C-2A), 68.0 (C-5C), 62.9 (C-6C), 61.9 (C-6A), 61.4 (C-6B), 20.7 (3
C), 20.6 (3 C), 20.5 (5 C) (11 COCH3). ESI-MS: 1005.2 [M + Na]+.
Anal. Calcd for C40H54O26S (982.26): C, 48.88; H, 5.54. Found: C,
48.70; H, 5.70.
Preparation of 2-Methyl-(3,4,6-tri-O-acetyl-1,2-dideoxy-α-D-
glucopyrano)-[2,1-d]-2-oxazoline (13a) from Compound 13.
To a solution of sodium sulfide (480 mg, 2.0 mmol) and carbon
disulfide (90 μL, 1.5 mmol) in DMF (5 mL) was added compound 13
(410 mg, 1.0 mmol), and it was stirred for 10 min at room
temperature. The reaction mixture was diluted with water and
extracted with EtOAc (50 mL), dried (Na2SO4), and concentrated to
furnish the crude product, which was purified over SiO2 using hexane−
EtOAc as eluant to give compound 13a (180 mg, 54%). Yellow oil;
[α]D = +16 (c 1.2, CHCl3) [Lit. [α]D = +15 (c 1.0, CHCl3)].39
Preparation of Bis-(2,3,4,6-tetra-O-acetyl-β-D-glucopyrano-
syl)-sulfide (15a). To a solution of sodium sulfide (480 mg, 2.0
mmol) and carbon disulfide (30 μL, 0.5 mmol) in DMF (5 mL) was
added compound 1 (410 mg, 1.0 mmol), and it was stirred for 5 min at
room temperature. The reaction mixture was diluted with water and
extracted with EtOAc (50 mL), dried (Na2SO4), and concentrated to
furnish the crude product, which was purified over SiO2 using hexane−
EtOAc as eluant to give compound 15a (420 mg, 60%). White solid;
mp 173−175 °C (EtOH) [Lit. 175−176 °C];40 [α]D = −37 (c 1.2,
CHCl3) [Lit. [α]D = −35.5 (CHCl3)].40
REFERENCES
■
(1) Pachamuthu, K.; Schmidt, R. R. Chem. Rev. 2006, 106, 160−187.
(2) (a) Dere, R. T.; Zhu, X. Org. Lett. 2008, 10, 4641−4644.
(b) Ding, Y.; Contour-Galcera, M. O.; Ebel, J.; Ortiz-Mellet, C.;
Defaye, J. Eur. J. Org. Chem. 1999, 1143−1152.
(3) Grayson, E. J.; Ward, S. J.; Hall, A. L.; Rendle, P. M.; Gamblin, D.
P.; Batsanov, A. S.; Davis, B. G. J. Org. Chem. 2005, 70, 9740−9754.
(4) Driguez, H. ChemBioChem 2001, 2, 311−318.
(5) Stallings-Mann, M.; Jamieson, L.; Regala, R. P.; Weems, C.;
Murray, N. R.; Fields, A. P. Cancer Res. 2006, 66, 1767−1774.
(6) Garegg, P. J. Adv. Carbohydr. Chem. Biochem. 1997, 52, 179−205.
(7) Caraballo, R.; Deng, L.; Amorim, L.; Brinck, T.; Ramstrom, O. J.
̈
Org. Chem. 2010, 75, 6115−6121.
(8) Taylor, R. J. K.; McAllister, G. D.; Franck, R. W. Carbohydr. Res.
2006, 341, 1298−1311.
(9) Lopez, M.; Drillaud, N.; Bornaghi, L. F.; Poulsen, S.-A. J. Org.
Chem. 2009, 74, 2811−2816.
(10) Colinas, P. A. Curr. Org. Chem. 2012, 16, 1670−1679.
(11) (a) Bernardes, G. J. L.; Grayson, E. J.; Thompson, S.; Chalker, J.
M.; Errey, J. C.; El Qualid, F.; Claridge, T. D. W.; Davis, B. G. Angew.
Chem., Int. Ed. Engl. 2008, 47, 2244−2247. (b) Stellenboom, N.;
Hunter, R.; Caira, M. R.; Szilag
5312.
́
yi, L. Tetrahedron Lett. 2010, 51, 5309−
(12) Wilkinson, B. L.; Fairbanks, A. J. Tetrahedron Lett. 2008, 49,
4941−4943.
(13) Lucas-Lopez, C.; Murphy, N.; Zhu, X. Eur. J. Org. Chem. 2008,
4401−4404.
(14) Aversa, M. C.; Barattucci, A.; Bilardo, M. C.; Bonaccorsi, P.;
Giannetto, P.; Rollin, P.; Tatibouet, A. J. Org. Chem. 2005, 70, 7389−
7396.
̈
(15) Pilgrim, W.; Murphy, P. V. Org. Lett. 2009, 11, 939−942.
(16) (a) Watt, G. M.; Lund, J.; Levens, M.; Kolli, V. S. K.; Jefferis, R.;
Boons, G.-J. Chem. Biol. 2003, 10, 807−814. (b) Rendle, P. M.; Seger,
A.; Rodrigues, J.; Oldham, N. J.; Bott, R. R.; Jones, J. B.; Cowan, M.
M.; Davis, B. G. J. Am. Chem. Soc. 2004, 126, 4750−4751.
(17) (a) Fiore, M.; Marra, A.; Dondoni, A. J. Org. Chem. 2009, 74,
4422−4425. (b) Floyd, N.; Vijayakrishnan, B.; Koeppe, J. R.; Davis, B.
G. Angew. Chem., Int. Ed. Engl. 2009, 48, 7798−7802.
(18) Johnston, B. D.; Pinto, B. M. J. Org. Chem. 2000, 65, 4607−
4617.
(19) Ibatullin, F. M.; Shabalin, K. A.; Janis, J. V.; Shavva, A. G.
Tetrahedron Lett. 2003, 44, 7961−7964.
(20) MacDougall, J. M.; Zhang, X. D.; Polgar, W. E.; Khroyan, T. V.;
Toll, L.; Cashman, J. R. J. Med. Chem. 2004, 47, 5809−5815.
(21) Holick, S. A.; Anderson, L. Carbohydr. Res. 1974, 34, 208−213.
(22) Defaye, J.; Gadelle, A.; Pedersen, C. Carbohydr. Res. 1991, 217,
51−58.
Preparation of Tri-O-acetyl-D-glucal (26) from Compound
12. To a solution of sodium sulfide (480 mg, 2.0 mmol) and carbon
disulfide (90 μL, 1.5 mmol) in DMF (5 mL) was added compound 12
(395 mg, 1.0 mmol), and it was stirred for 5 min at room temperature.
The reaction mixture was diluted with water and extracted with EtOAc
(50 mL), dried (Na2SO4), and concentrated to furnish the crude
product, which was purified over SiO2 using hexane−EtOAc as eluant
to give compound 26 (256 mg, 94%). White solid; mp 51−53 °C
(hexane−Et2O) [Lit. mp 50−51 °C];41 [α]D = −24 (c 1.2, CHCl3)
[Lit. [α]D = −22 (c 4.1, CHCl3)].41
̈
F
dx.doi.org/10.1021/jo302115k | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
(23) Bernardes, G. J. L.; Gamblin, D. P.; Davis, B. G. Angew. Chem.,
Int. Ed. Engl. 2006, 45, 4007−4011.
(24) Dere, R. T.; Wang, Y.; Zhu, X. Org. Biomol. Chem. 2008, 6,
2061−2063.
(25) Zhu, X.; Dere, R. T.; Jiang, J.; Zhang, L.; Wang, X. J. Org. Chem.
2011, 76, 10187−10197.
(26) Dere, R. T.; Kumar, A.; Kumar, V.; Zhu, X.; Schmidt, R. R. J.
Org. Chem. 2011, 76, 7539−7545.
(27) Bogusiak, J.; Szeja, W. Carbohydr. Res. 1985, 141, 165−167.
(28) Bock, K.; Pederson, C. J. Chem. Soc., Perkin Trans 2 1974, 293−
297.
(29) (a) Galonic, D. P.; van der Donk, W. A.; Din, D. Y. Chem.Eur.
J. 2003, 9, 5997−6006. (b) Bernardes, G. J. L.; Chalker, J. M.; Errey, J.
C.; Davis, B. G. J. Am. Chem. Soc. 2008, 130, 5052−5053. (c) Wang, J.;
Schiller, S. M.; Schultz, P. G. Angew. Chem., Int. Ed. Engl. 2007, 46,
6849−6851. (d) Chalker, J. M.; Gunnoo, S. B.; Boutureira, O.;
Gerstberger, S. C.; Fernandez-Gonzalez, M.; Bernardes, G. J. L.;
Griffin, L.; Hailu, H.; Schofield, C. J.; Davis, B. G. Chem. Sci. 2011, 2,
1666−1676.
(30) Rillahan, C. D.; Paulson, J. C. Annu. Rev. Biochem. 2011, 80,
797−823.
(31) Cerny, M.; Stanek, J.; Pacak, J. Monatsh. Chem. 1963, 94, 290−
294.
(32) Zhu, X.; Schmidt, R. R. J. Org. Chem. 2004, 69, 1081−1085.
(33) Cai, Y.; Roberts, B. P.; Tocher, D. A. J. Chem. Soc., Perkin Trans.
1 2002, 1376−1386.
(34) Ponpipom, M. M.; Bugianesi, R. L.; Blake, T. J. J. Med. Chem.
1987, 30, 705−710.
(35) Meng, X.-B.; Yang, L.-D.; Li, H.; Li, Q.; Cheng, T.-M.; Cai, M.-
S.; Li, Z.-J. Carbohydr. Res. 2002, 337, 977−981.
(36) Fujihira, T.; Chida, M.; Kamijo, H.; Takido, T.; Seno, M. J.
Carbohydr. Chem. 2002, 21, 287−292.
(37) Ferrier, R. J.; Furneaux, R. H.; Tyler, P. C. Carbohydr. Res. 1977,
58, 397−404.
(38) Prade, H.; Mackenzie, L. F.; Withers, S. G. Carbohydr. Res. 1997,
305, 371−381.
(39) Seibel, J.; Hillringhaus, L.; Moraru, R. Carbohydr. Res. 2005, 340,
507−511.
(40) Masakatsu, S.; Masanobu, H.; Setsuzo, T.; Masuo, A. Chem.
Pharm. Bull. 1964, 12, 652−656.
(41) Zhao, J.; Wei, S.; Ma, X.; Shao, H. Carbohydr. Res. 2010, 345,
168−171.
G
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