Synthesis of Deoxyglycosides by Desulfurization under UV Light

Article abstract of DOI:10.1021/acs.joc.7b00896

This study was performed to develop a highly efficient method whereby desulfurization could be completed in 0.5 h under ultraviolet light, at room temperature, and in the presence of trialkylphosphine. Using this method, deoxyglycosides could be produced from sulfur-containing glycosides in almost quantitative yields. The much higher reactivity of desulfurization with triethylphosphine versus that with triethylphosphite is also discussed.

Full text of DOI:10.1021/acs.joc.7b00896

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Synthesis of Deoxy Glycosides by Desulfurization under UV-Light
Jian-Tao Ge, Ying-Ying Li, Jun Tian, Rong-Zhen Liao, and Hai Dong
J. Org. Chem., Just Accepted Manuscript • Publication Date (Web): 09 Jun 2017
Downloaded from http://pubs.acs.org on June 9, 2017
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Synthesis of Deoxy Glycosides by Desulfurization under
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JianꢀTao Ge, YingꢀYing Li, Jun Tian, RongꢀZhen Liao, and Hai Dong*
Key laboratory of Material Chemistry for Energy Conversion and Storage, Ministry of Education,
School of Chemistry & Chemical Engineering, Huazhong University of Science & Technology, Luoyu
Road 1037, Wuhan, 430074, P. R. China
hdong@mail.hust.edu.cn
RECEIVED DATE (to be automatically inserted after your manuscript is accepted if required
according to the journal that you are submitting your paper to)
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ABSTRACT
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This study was performed to develop a highly efficient method whereby desulfurization could be
completed in 0.5 hours under ultraviolet light, at room temperature, and in the presence of
trialkylphosphine. Using this method, deoxy glycosides could be produced from sulfurꢀcontaining
glycosides in almost quantitative yields. The much higher reactivity of desulfurization with
triethylphosphine versus triethylphosphite was also discussed.
Deoxy glycosides are frequently the main constituents of glycosidic chains in many biologically
active natural products, including antibiotics and cardiac glycosides, in which they are thought to play
significant roles in bioactivity.1ꢀ4 Consequently, the synthesis of deoxy sugars and further synthesis of
related natural products, particularly 2ꢀdeoxy glycosides and their derivatives, has been identified as an
important and challenging area of carbohydrate chemistry.5ꢀ15 Several deoxy sugar production methods
have been reported, including the reduction of glycals,16 glycoꢀepoxides,17 and glycosides with
halides18ꢀ22 and thiocarbonyl group,23ꢀ28 all of which have their respective advantages and shortcomings
(Scheme 1a). Hydrogenolytic desulfurization, catalyzed by either Raney nickel or Pd/Al2O3, was first
used to synthesize unprotected peptide segments via native chemical ligation.29ꢀ31 Later, a
desulfurization method involving trisꢀ(2ꢀcarboxyethyl) phosphine (TCEP) and a radical initiator was
developed to overcome the shortcomings of the Raney nickel or palladium method.32,33
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The Journal of Organic Chemistry
We recently noticed a report in which Raney nickelꢀcatalyzed desulfurization was used to produce 2ꢀ
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deoxy β βꢀstereoselectivity.
ꢀdisaccharides,34,35 wherein Cꢀ2 thioacetate group participation controlled
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However, desulfurization was otherwise rarely reported regarding deoxy glycoside synthesis, possibly
because of a lack of efficient means to obtain sulfurꢀcontaining glycosides. In this study, we developed a
UV lightꢀtriggered desulfurization method (Scheme 1b) whereby sulfurꢀcontaining glycosides could be
completely desulfurized within 0.5 h at room temperature and in the presence of trialkylphosphines
(PEt3). We then used this method to synthesize almost quantitative yields of various deoxy glycosides.
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Scheme 1. Methods for deoxy glycoside synthesis
We have been making an efforts to develop methods for sulfurꢀcontaining glycoside synthesis over
the years,36ꢀ39 which inspired us to explore the efficient method of deoxy glycoside synthesis via
desulfurization of sulfurꢀcontaining glycosides. More importantly, because Cꢀ2 thioacetate group
participation can effectively control the stereochemistry of disaccharide formation,34 it should be simple
to construct 2ꢀdeoxy disaccharides with excellent α/βꢀselectivity via a glycosylation donor with a Cꢀ2
thioacetate group, followed by efficient desulfurization (Scheme 1c). In the 1950s, Hoffmann et al.
identified a desulfurization reaction promoted by trialkylphosphite derivatives under thermal or
photochemical conditions,40 and Walling and Rabinowitz proposed a radical reaction mechanism shortly
thereafter.41ꢀ43 Based on those findings, we hypothesized that deoxy glycosides could be obtained by
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treating sulfurꢀcontaining glycosides with P(OEt)3 under UV light. We initially tested methyl 6ꢀthioꢀαꢀ
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D
ꢀglucoside 1a in our proposed desulfurization reaction to explore optimized conditions (Table 1). The
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reactions were performed in a commercial photochemistry reactor with a 500ꢀwatt mercury lamp and
cooling circuit (all glassware are pyrex). However, although complete desulfurization with P(OEt)3 was
reported under irradiation from a 100ꢀwatt Sꢀ4 bulb within 6.25 h,40 or from a 300ꢀwatt visible light
bulb within 36 h,44 our experiments with P(OEt)3 were unsuccessful (Entries 1 ꢀ3 in Table 1).
Surprisingly, compound 1a was successfully desulfurized under UV light in the presence of PEt3 instead
(Entries 4 ꢀ 8). Using the solvent DMF, which yielded the best results, we obtained a quantitative
desulfurization yield of compound 1a in the presence of 1.6 equiv. of PEt3 (Entry 8). Although methanol
could also be used as the solvent, 3.0 equiv. of PEt3 were required to obtain a quantitative yield of
compound 2a (Entry 9). Other trialkylphosphines, including tributylphosphine and TCEP, also led to
good yields (Entries 10 and 11). However, triphenylphosphine and tris(diethylaꢀmino)phosphine yielded
no or little desulfurization (Entries 12 and 13). These reactions did not occur under visible light (Entry
14), and the desulfurization yield decreased by 35% (30ꢀmin reaction) when the power of the mercury
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lamp decreased by 200ꢀwatt (Entry 15). We also tested methyl 2,3,4ꢀtriꢀOAcꢀ6ꢀthioꢀαꢀDꢀglucoside 1b
under a 200ꢀwatt UV light (Entry 16) and achieved a result identical to that obtained with 1a, indicating
that groups in other positions had no effect on desulfurization. A complex mixture was obtained when
the reaction was performed with a radical initiator (AIBN) likely due to more sideꢀreactions aroused by
o
higher reaction temperature (50ꢀ70 C) (Entry 17). Regarding solvents, our previous experiments
indicated that in this reaction DMF was superior to methanol, likely due to a higher oxygen level in
methanol. For confirmation, we performed desulfurization reactions both in normal and degassed
methanol (Entries 18 and 19). As expected, the desulfurization yield with degassed methanol increased
quantitatively from the 55% yield with normal methanol. Ultimately, we selected 1.6 equiv. of PEt3 per
thiol group, a 30ꢀmin reaction time, and DMF as the optimized conditions.
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Table 1 Comparison of results by variation of reaction conditionsa
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Entry Reagent (equiv.) Solvent Time (min.) Yield %
ꢀg
ꢀg
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5
P(OEt)3 (1.2)
P(OEt)3 (1.2)
P(OEt)3 (1.2)
PEt3 (1.2)
PEt3 (1.2)
PEt3 (1.2)
MeOH
Acetone
DMF
MeOH
Acetone
DMF
30 ꢀ 120
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30
ꢀg
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36
81
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7
PEt3 (1.4)
DMF
30
92
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12
PEt3 (1.6)
PEt3 (3.0)
PBu3 (1.6)
TCEP (1.6)
PPh3 (1.6)
DMF
MeOH
DMF
DMF
DMF
30
30
30
30
Quant.
Quant.
Quant.
90
30
0
13
14b
15c
16c,d
17e
18
P(NEt2)3 (1.6)
P(Et)3 (1.6)
P(Et)3 (1.6)
P(Et)3 (1.6)
P(Et)3 (1.6)
P(Et)3 (1.8)
P(Et)3 (1.8)
DMF
DMF
DMF
DMF
DMF
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30
30
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30
20
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25
ꢀg
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35
ꢀh
MeOH
MeOH
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Quant.
19f
a
b
c
Reaction conditions: Substrate 1a (50 mg, 0.24 mmol), solvent (1 mL), 500ꢀwatt mercury lamp, r.t. Visible light.
200ꢀwatt mercury lamp. d Substrate 1b (80 mg, 0.24 mmol). e AIBN (0.3 equiv), 50 – 70 oC. f Degassed by vacuum and
then filled with N2. g No reaction. h Complex mixture.
We next performed experiments under optimized conditions (Figure 1) to desulfurize methyl 6ꢀthio
glycopyranosides 3, 5, 7 and 9; methyl 2ꢀthio glycopyranosides 11 and 13; methyl 4ꢀthio
glycopyranosides 15, 17, 19 and 20; 3ꢀthio glycopyranoside 21; 2,4ꢀdithio glycopyranosides 23 and 25;
and 1ꢀthio glycopyranosides 27 and 29. We achieved excellent isolation yields (> 90%) for desulfurized
compounds 3, 5, 7, 9, 11, 13, 15, 17, 19, 20 and 21 (TLC indicating full conversion) and relative low
yields (55 – 58%) for the dithio glycosides 23 and 25 because of complicated side products. We still
achieved a high isolated yield (98%) from largeꢀscale testing of 6ꢀthioꢀαꢀDꢀglucoside 1 (1 g), thus
demonstrating the method’s robustness. Unexpectedly, although the desulfurization of 1ꢀthio
glycopyranosides 27 lead to the highꢀyield synthesis (89%) of deoxy glycoside 28, the desulfurization of
1ꢀthio 2,3,4,6ꢀtetraꢀOAcꢀglycosides 29 led to complex mixtures likely due to the migration of acetyl
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group.45,46 The disulfide dimer 30 (dimer 13ꢀ13) was also tested under these conditions, leading to a
highꢀyield (95%) isolation of deoxy glycoside 14 and indicating that our method could be used to
desulfurize disulfide dimers. These results differed from those of an earlier report by Walling in which
P(OEt)3 led to sulfide production.41ꢀ43 Our experiments have shown that P(OEt)3 could not lead to UV
excited desulfurization. In light of Walling’s report, the reaction between thiyl radicals and P(Et)3 is
about 6 time faster than the reaction with P(OEt)3.43 As we used excess amounts of PEt3 (1.6 equiv. per
thiol group) in our case, it is probably that there are high concentration of thiyl radical in Walling’s case
whereas low concentration of thiyl radical in our case since the thiyl radical will be consumed by P(Et)3
immediately once it forms. As a result, there are no sulfides found in our experiments. Furthermore, we
performed deuteration experiments and demonstrated that the captured hydrogen atom by deoxy
glycoside 14 came from trace water in the solvents (Figure S1 in SI). It is because that PEt3 cleaves the
disulfide according to the classical two electron process,47 and hydrolysis of the intermediates by the
water generates two equivalents of thiol. These are then desulfurized in the same manner as the other
thiols in Figure 1.
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Figure 1. UVꢀlight promoted synthesis of deoxy glycosides.a React condition: a Substrate (50 mg), P(Et)3 (1.6
equiv.), DMF (1 mL), 500ꢀwatt mercury lamp, r.t., 0.5 h. b Substrate (50 mg), P(Et)3 (3.0 equiv.), mathanol (1 mL),
500ꢀwatt mercury lamp, r.t., 0.5 h.
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The Journal of Organic Chemistry
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Though additional PEt3 is needed for desulfurization when methanol is used as the solvent, this
solvent is usually superior to DMF because it is easily removed from the reaction mixture. Therefore,
we tested desulfurization using 3.0 equiv. of PEt3 per thiol group, a 30ꢀmin reaction time, and methanol.
Under these conditions, we observed somewhat lower yields of deoxy products following the
desulfurization of compounds 5, 9, 11, 13, 15, 17, 23, 25 and 30 (due to trace sideꢀproducts). For
example, a small amount of the side product methyl αꢀgalactoside 31 was observed in the
desulfurization of compound 5. No reactions were observed in the desulfurization of compound 3, 7,
and 20. These unexpected results might be attributable to the oxygen present in methanol.
Similar to Walling and Rabinowitz proposed radical reaction mechanism,41ꢀ43 the desulfurization with
PEt3 via phosphoranyl radical intermediate was shown in eqs 1ꢀ5.
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To further understand differences in desulfurization reactivities with PEt3 and with P(OEt)3, density
functional calculations were performed using ethylsulfanyl radical to mimic the sulfurꢀcontaining
glycoside radical generated upon UV excitation (see SI for details). Here, a complex (phosphoranyl
radical) forms between the two reactants, with partial electron transfer from the phosphorus moiety to
the sulfur center. Reaction approaches involving two different phosphoranyl radical configurations
suggested by Giles and Robert48 were compared in the calculation, supporting a lower barrier of
transition state in desulfurization with PEt3. In addition, the lower desulfurization reactivity with
P(OEt)3 may be attributed to βꢀoxygen effect,49ꢀ51 because there is a strong possibility that the
phosphoranyl radical obtained by thiyl radical addition to P(OEt)3 could undergo competing decay by
fragmentation of a CꢀO bond to give an ethyl radical and a P=O bond. This is exactly the type of
competition (CꢀO vs CꢀS fragmentation) that occurs in xanthate reduction.52,53 This pathway is not
available in the PEt3 series.
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In conclusion, we have developed a highly efficient method for desulfurizing thioꢀcontaining
glycosides under UV light and in the presence of 1.6 equiv. of PEt3 in DMF. Using this method, we
could generally obtain quantitative yields of desulfurization products after 30ꢀmin reactions in a
commercial photochemistry reactor and could synthesize deoxy glycosides with high efficiency. This
method may provide a new approach to synthesize 2ꢀdeoxy glycosides (Scheme 1c) via the
stereoselective control of Cꢀ2 thioacetate groups.
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Experimental section
General: All commercially available starting materials and solvents were of reagent grade and used
without further purification. Chemical reactions were monitored with thinꢀlayer chromatography using
precoated silica gel 60 (0.25 mm thickness) plates. Flash column chromatography was performed on
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silica gel 60 (SDS 0.040ꢀ0.063 mm). H NMR spectra were recorded at 298K in CDCl3 and D2O, using
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the residual signals from CHCl3 (1H: = 7.26 ppm) and D2O (1H: = 4.80 ppm) as internal standard. H
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peak assignments were made by first order analysis of the spectra, supported by standard Hꢀ1H
correlation spectroscopy (COSY).
General deacylation of thiolacetate carbohydrate derivatives:37 Sodium hydroxide (1.1 equiv for
each of thioacetyl groups) was added in the solution of acylated thioꢀcontaining methyl
Dꢀglycoside
derivatives in methanol. The reaction mixture was stirred at room temperature for 4ꢀ8 h under nitrogen
protection and monitored with TLC. Then the mixture was neutralized with Amberlite IRꢀ120 (H+) ion
exchange resin and filtered. DTT (3.0ꢀ5.0 equiv) was added to the filtration. The mixture was stirred at
room temperature for 12 h. The solvent was removed under vacuum. Purification of the residue by flash
column chromatography (CH2Cl2/MeOH 30:1ꢀ100:1) afforded the deprotected products.
General procedure of desulfurization reaction under UV light: Substrates (50 mg) were allowed to
react with triethylphosphine (1.6 – 2.0 equiv. to per thiol group) in DMF/methanol (0.5 mL) under UV
light (a photochemistry reactor with a 500ꢀwatt mercury lamp and a cooling circuit) at room temperature
for 30 minutes. The reaction mixture was concentrated in vacuo. The residue was directly purified by
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The Journal of Organic Chemistry
flash column chromatography (EtOAcꢀCH3OH = 30:1 to 100:1) to afford the pure products.
Large scale: Thioꢀglucoside 1a (1 g) were allowed to react with triethylphosphine (1.1 mL) in DMF (6
mL) under UV light (a photochemistry reactor with a 500ꢀwatt mercury lamp and a cooling circuit) at
room temperature for 30 minutes. The reaction mixture was concentrated in vacuo. The residue was
directly purified by flash column chromatography (EtOAc : CH3OH = 30:1 to 100:1) to afford the pure
product 2a (0.83 g, 98% yield).
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Methyl 6ꢀthioꢀαꢀ
D
ꢀglucopyranoside 1a54: Methyl 4ꢀOꢀacetylꢀ6ꢀSꢀacetylꢀαꢀ
Dꢀglucopyranoside
(colorless syrup) was synthesized via methyl 6ꢀtosylꢀαꢀDꢀglucopyranoside starting from methyl αꢀDꢀ
glucopyranoside in light of reference.38 Sodium hydroxide (1.1 equiv, 75 mg) was added in the solution
of methyl 4ꢀOꢀacetylꢀ6ꢀSꢀacetylꢀαꢀDꢀglucopyranoside (500 mg, 1.7 mmol) in methanol, performed as
described in the general deacylation of thiolacetate carbohydrate derivatives. Purification of the residue
by flash column chromatography (CH2Cl2/MeOH= 30:1) afforded 1a (318 mg, 89%) as colorless oil. 1H
NMR (D2O, 400 MHz): δ = 4.70 (Hꢀ1, in water peak), 3.63ꢀ3.50 (m, 2H, Hꢀ5, Hꢀ3), 3.48 (dd, 1H, J =
9.7 Hz, Hꢀ2), 3.30 (t, J = 9.2 Hz, 1H, Hꢀ4), 3.34 (s, 3H, OMe), 2.90 (dd, J = 14.2 Hz, 1.2 Hz, 1H, Hꢀ6a),
2.63 (dd, J = 14.2 Hz, 7.4 Hz, 1H, Hꢀ6b) ppm; 13C NMR(CD3OD, 100 MHz): δ = 99.9, 73.6, 72.7, 72.3,
72.2, 54.2, 25.6 ppm. HRMS (ESIꢀTOF) m/z: [M + Na]+ Calcd for C7H14O5SNa 233.0460; found
233.0461.
Methyl 6ꢀdeoxyꢀαꢀD Dꢀglucopyranoside 1a
ꢀglucopyranoside 2a28: To a solution of methyl 6ꢀthioꢀαꢀ
(100 mg, 0.48 mmol) and P(Et)3 (130 uL, 0.77 mmol) in DMF (1mL), performed as described in the
general procedure of desulfurization reaction under UV light, affording 2a as colorless oil (elution with
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methanol / ethyl acetate = 1:30 (v/v); 83.7 mg, 98% yield). H NMR (D2O, 400 MHz) δ = 4.66 (Hꢀ1, in
water peak), 3.76ꢀ3.50 (m, 3H, Hꢀ2, Hꢀ4, Hꢀ5), 3.40 (s, 3H, OMe), 3.14 (t, J = 8.8 Hz, 1H, Hꢀ3), 1.27 (d,
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J = 6.2 Hz, 3H, Hꢀ6) ppm; C NMR (CD3OD, 100 MHz) δ = 99.9, 76.0, 73.5, 72.4, 67.2, 54.1, 16.6
ppm. HRMS (ESIꢀTOF) m/z: [M + Na]+ Calcd for C7H14O5Na 201.0739; found 201.0731.
Methyl 2,3,4ꢀTriꢀOꢀacetylꢀ6ꢀdeoxyꢀαꢀDꢀglucopyranoside 2b55: To a solution of methyl 2,3,4ꢀTriꢀOꢀ
acetylꢀ6ꢀthioꢀαꢀ
D
ꢀglucopyranoside 1b56 (120 mg, 0.36 mmol) and P(Et)3 (100 uL, 0.77 mmol) in DMF
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(1 mL), performed as described in the general procedure of desulfurization reaction under UV light,
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affording 2b as white solid (elution with ethyl acetate/petroleum ether = 1:5 (v/v); 105 mg, 96%). H
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NMR (CDCl3, 400 MHz) δ = 5.43 (dd, J = 10.4 Hz, 1H, Hꢀ3), 4.93ꢀ4.84 (m, 2H, Hꢀ1, Hꢀ2), 4.80 (t, J =
9.6 Hz, 1H, Hꢀ4), 3.88 (dq, J = 9.6 Hz, 1H, Hꢀ5), 3.40 (s, 3H, OMe), 1.20 (d, J = 6.4 Hz, 3H, Hꢀ6) ppm;
13C NMR (CD3OD, 100 MHz) δ = 170.2, 170.1, 169.8, 96.6, 73.8, 71.2, 70.1, 64.9, 55.2, 22.4, 20.7,
20.6, 17.2 ppm. HRMS (ESIꢀTOF) m/z: [M + Na]+ Calcd for C13H20O8Na 327.1056; found 327.1053.
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Methyl 6ꢀthioꢀβꢀ
D
ꢀglucopyranoside 3: Sodium hydroxide (1.1 equiv, 75 mg) was added in the solution
ꢀglucopyranoside38 (500 mg, 1.7 mmol) in methanol, performed as
of methyl 4ꢀOꢀacetylꢀ6ꢀSꢀacetylꢀβꢀ
D
described in the general deacylation of thiolacetate carbohydrate derivatives. Purification of the residue
by flash column chromatography (CH2Cl2/MeOH = 30:1) afforded 3 (314 mg, 89%) as colorless oil.
[α]D25 = −23.1 (c = 2.0 in CH3OH); 1H NMR (D2O, 400 MHz) δ = 4.25 (d, J = 8.0 Hz, 1H, Hꢀ1), 3.45 (s,
3H, OMe), 3.37ꢀ3.23 (m, 3H, Hꢀ3, Hꢀ4, Hꢀ5), 3.11 (dd, 1H, J = 8.0 Hz , 9.2 Hz, Hꢀ2), 2.86 (dd, J = 2.4
Hz, 14.4 Hz, 1H, Hꢀ6a), 2.58 (dd, J = 7.2 Hz, 14.4 Hz, 1H, Hꢀ6b) ppm; 13C NMR (CD3OD, 100 MHz) δ
= 103.9, 76.5, 76.4, 73.8, 72.4, 55.9, 25.6 ppm. IR (film) v = 3360, 2920, 1662, 1447, 1395, 1074, 931,
614 cm−1. HRMS (ESIꢀTOF) m/z: [M + Na]+ Calcd for C7H14O5SNa 233.0460; found 233.0455.
Methylꢀ6ꢀdeoxyꢀβꢀDꢀglucopyranoside 457: To a solution of methyl 6ꢀthioꢀβꢀ
Dꢀglucopyranoside 3 (56
mg, 0.27 mmol) and P(Et)3 (74 uL, 0.44 mmol) in DMF (0.6 mL), performed as described in the general
procedure of desulfurization reaction under UV light, affording 4 as colorless oil (elution with methanol
1
/ ethyl acetate = 1:30 (v/v); 46 mg, 95% yield). H NMR (D2O, 400 MHz) δ = 4.24 (d, J = 7.8 Hz, 1H,
Hꢀ1), 3.44 (s, 3H, OMe), 3.41ꢀ3.30 (m, 2H, Hꢀ3, Hꢀ5), 3.14 (t, J = 8.4 Hz, 1H, Hꢀ2), 3.14 (t, J = 9.2 Hz,
1H, Hꢀ4), 1.27 (d, J = 6.4 Hz, 3H, Hꢀ6) ppm; 13C NMR (CD3OD, 100 MHz) δ = 103.9, 76.4, 75.6, 73.9,
71.9, 55.8, 16.6 ppm. HRMS (ESIꢀTOF) m/z: [M + Na]+ Calcd for C7H14O5Na 201.0739; found
201.0734.
Methyl 6ꢀthioꢀαꢀDꢀgalactopyranoside 5: Sodium hydroxide (1.1 equiv, 58 mg) was added in the
solution of methyl 2,3,4ꢀtriꢀOꢀacetylꢀ6ꢀSꢀacetylꢀαꢀD
ꢀgalactopyranoside58 (500 mg, 1.32 mmol) in
methanol, performed as described in the general deacylation of thiolacetate carbohydrate derivatives.
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Purification of the residue by flash column chromatography (CH2Cl2/MeOH = 30:1) afforded 5 (236 mg,
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25
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85%) as colorless oil. [α]D = +79.3 (c = 2.0 in CH3OH); H NMR (D2O, 400 MHz) δ = 4.75 (Hꢀ1, in
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water peak), 3.98 (s, 1H, Hꢀ3), 3.80ꢀ3.74 (m, 3H, Hꢀ5, Hꢀ2, Hꢀ4), 3.37 (s, 3H, OMe), 2.68 (m, 2H, Hꢀ6a,
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8
13
Hꢀ6b) ppm; C NMR (D2O, 100 MHz) δ = 99.5, 72.2, 69.6, 69.5, 68.1, 55.2, 23.9 ppm. IR (film) v =
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3412, 2925, 2854, 1662, 1418, 1362, 1044, 939, 662 cm−1. HRMS (ESIꢀTOF) m/z: [M + Na]+ Calcd for
C7H14O5SNa 233.0460; found 233.0460.
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Methyl 6ꢀdeoxyꢀαꢀD Dꢀgalactopyranoside 5
ꢀgalactopyranoside 657: To a solution of methyl 6ꢀthioꢀαꢀ
(55 mg, 0.26 mmol) and P(Et)3 (74 uL, 0.43 mmol) in DMF (0.6 mL), performed as described in the
general procedure of desulfurization reaction under UV light, affording 6 as colorless oil (elution with
methanol / ethyl acetate = 1:30 (v/v); 42 mg, 90% yield). 1H NMR (D2O, 400 MHz) δ = 4.65 (d, J = 3.2
Hz, 1H, Hꢀ1), 3.92 (dd, J = 6.4 Hz, 13.2 Hz, 1H, Hꢀ5), 3.73ꢀ3.64 (m, 3H, Hꢀ2, Hꢀ3, Hꢀ4), 3.28 (s, 3H,
13
OMe), 1.11 (d, J = 6.4 Hz, 3H, Hꢀ6) ppm; C NMR (D2O, 100 MHz) δ = 99.5, 71.8, 69.6, 67.9, 66.5,
55.1, 15.3 ppm. HRMS (ESIꢀTOF) m/z: [M + Na]+ Calcd for C7H14O5Na 201.0739; found 201.0733.
Methyl 6ꢀthioꢀβꢀDꢀgalactopyranoside 7: Sodium hydroxide (1.1 equiv, 58 mg) was added in the
solution of methyl 2,3,4ꢀtriꢀOꢀacetylꢀ6ꢀSꢀacetylꢀβꢀDꢀgalactopyranoside (500 mg, 1.32 mmol) in
methanol, performed as described in the general deacylation of thiolacetate carbohydrate derivatives.
Purification of the residue by flash column chromatography (CH2Cl2/MeOH = 30:1) afforded 7 (236 mg,
85%) as white solid. Although this compound has been reported in literatures,39 its full spectroscopic
data are not available. [α]D25 = ꢀ10.5 (c = 1.5 in CH3OH); mp = 114−115°C; 1H NMR (D2O, 400 MHz)
δ = 4.20 (d, J = 8 Hz, 1H, Hꢀ1), 3.91 (d, J = 3.2 Hz, 1H, Hꢀ4), 3.52 (m, 2H, Hꢀ3, Hꢀ5), 3.46 (s, 3H,
OMe), 3.37 (dd, 1H, Hꢀ2), 2.72 (dd, J = 7.6 Hz, 13.6 Hz, 1H, Hꢀ6a), 2.59 (dd, J = 6.0 Hz , 13.6 Hz, 1H,
Hꢀ6b) ppm; 13C NMR (D2O, 100 MHz) δ = 103.8, 76.4, 72.8, 70.6, 68.9, 57.2, 23.7 ppm. IR (film) v =
3359, 2917, 2868, 1647, 1419, 1397, 1057, 900, 656 cm−1. HRMS (ESIꢀTOF) m/z: [M + Na]+ Calcd for
C7H14O5SNa 233.0460; found 233.0462.
Methyl 6ꢀdeoxyꢀβꢀD Dꢀgalactopyranoside 7
ꢀgalactopyranoside 857: To a solution of methyl 6ꢀthioꢀβꢀ
(55 mg, 0.26 mmol) and P(Et)3 (74 uL, 0.43 mmol) in DMF (0.6 mL), performed as described in the
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general procedure of desulfurization reaction under UV light, affording 8 as colorless oil (elution with
methanol / ethyl acetate = 1:30 (v/v); 44 mg, 96% yield). 1H NMR (D2O, 400 MHz) δ = 4.18 (d, J = 7.6
Hz, 1H, Hꢀ1), 3.68 (q, J = 6.4 Hz, 1H, Hꢀ5), 3.63 (dd, J = 3.2 Hz, 1H, Hꢀ4), 3.53(dd, J = 3.2 Hz, 9.2 Hz,
1H, Hꢀ3), 3.43 (s, 3H, OMe), 3.34 (dd, J = 7.6 Hz, 9.2 Hz, 1H, Hꢀ2), 1.15 (d, J = 6.4 Hz, 3H, Hꢀ6) ppm;
13C NMR (CD3OD, 100 MHz) δ = 104.5, 73.8, 71.6, 70.9, 70.5, 55.7, 15.3 ppm. HRMS (ESIꢀTOF) m/z:
[M + Na]+ Calcd for C7H14O5Na 201.0739; found 201.0733.
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Methyl 6ꢀdeoxyꢀαꢀD D
ꢀmannopyranoside 1057: To a solution of methyl 6ꢀthioꢀαꢀ ꢀmannopyranoside 936
(96 mg, 0.46 mmol) and P(Et)3 (130 uL, 0.74 mmol) in DMF (1 mL), performed as described in the
general procedure of desulfurization reaction under UV light, affording 10 as colorless oil (elution with
methanol / ethyl acetate = 1:30 (v/v); 77.8 mg, 95% yield). Analytical data found for 10 are in
1
accordance with those reported previously. H NMR (D2O, 400 MHz) δ = 4.66 (d, J = 1.7 Hz, 1H, Hꢀ1),
3.78 (dd, J = 3.5, 1.7 Hz, 1H, Hꢀ2), 3.61 (dd, J = 9.4, 3.5 Hz, 1H, Hꢀ3), 3.57ꢀ3.48 (m, 1H, Hꢀ5), 3.38 (pt,
J = 9.5 Hz, 1H, Hꢀ4), 3.35 (s, 3H, OMe), 1.27 (d, J = 6.2 Hz, 3H, Hꢀ6) ppm; 13C NMR (D2O, 100 MHz)
δ = 101.4, 72.6, 71.0, 70.8, 68.2, 53.7, 16.8 ppm. HRMS (ESIꢀTOF) m/z: [M + Na]+ Calcd for
C7H14O5Na 201.0739; found 201.0734.
Methyl 2ꢀdeoxyꢀβꢀD Dꢀmannopyranoside
ꢀmannopyranoside 1259: To a solution of methyl 2ꢀthioꢀβꢀ
1136 (50 mg, 0.24 mmol) and P(Et)3 (68 uL, 0.39 mmol) in DMF (0.5 mL), performed as described in the
general procedure of desulfurization reaction under UV light, affording 12 as colorless oil (elution with
1
methanol / ethyl acetate = 1:30 (v/v); 41 mg, 96% yield). H NMR (D2O, 400 MHz) δ = 4.54 (dd, J =
2.0 Hz, 10.0 Hz, 1H, Hꢀ1), 3.84 (dd, J = 2.0 Hz, 12.0 Hz, 1H, Hꢀ4), 3.67ꢀ3.59 (m, 2H, Hꢀ3, Hꢀ5), 3.43 (s,
3H, OMe), 3.28 (m, 1H, Hꢀ6a), 3.16 (m, 1H, Hꢀ6b), 2.16 (ddd, J = 1.6 Hz, 4.8 Hz, 12.4 Hz, 1H, Hꢀ2a),
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1.67 (ddd, J = 9.8 Hz, 12.0 Hz,12.0 Hz, 1H, Hꢀ2b) ppm; C NMR (D2O, 100 MHz) δ = 100.8, 76.6,
71.7, 71.1, 61.6, 55.4, 38.9 ppm. HRMS (ESIꢀTOF) m/z: [M + Na]+ Calcd for C7H14O5Na 201.0739;
found 201.0734.
Methyl 2ꢀdeoxyꢀαꢀD Dꢀ
ꢀmannopyranoside 1460: Procedure A: to a solution of methyl 2ꢀthioꢀαꢀ
mannopyranoside 1336 (73 mg, 0.35 mmol) and P(Et)3 (98 uL, 0.56 mmol) in DMF (0.7 mL), performed
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as described in the general procedure of desulfurization reaction under UV light, affording 14 as white
solid (elution with methanol / ethyl acetate = 1:30 (v/v); 59 mg, 95% yield). Procedure B: to a solution
of (methyl 2ꢀthioꢀαꢀmannopyranosyl)ꢀ(methyl 2ꢀthioꢀαꢀmannopyranosyl) disulfide 31 (50 mg, 0.12
mmol) and P(Et)3 (110 uL, 0.56 mmol) in DMF (0.6 mL), performed as described in the general
procedure of desulfurization reaction under UV light, affording 14 as white solid (elution with methanol
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1
/ ethyl acetate = 1:30 (v/v); 40 mg, 95% yield). H NMR (D2O, 400 MHz) δ = 4.78 (d, J = 3.2 Hz, 1H,
Hꢀ1), 3.78ꢀ3.69 (m, 2H, Hꢀ3, Hꢀ6a), 3.64 (m, 1H, Hꢀ6b), 3.47 (m, 1H, Hꢀ5), 3.26ꢀ3.18 (m, 1H, Hꢀ4),
3.23 (s, 3H, OMe), 2.10 (dd, J = 5.2 Hz, 13.6 Hz, 1H, Hꢀ2a), 1.67 (ddd, J =4.0 Hz, 12.4 Hz,13.6 Hz, 1H,
Hꢀ2b) ppm.
Methyl 4ꢀdeoxyꢀβꢀ
D
ꢀxyloꢀhexopyranoside 1661: To a solution of methyl 4ꢀthioꢀβꢀ
D
ꢀgalactopyranoside
1539 or methyl 4ꢀthioꢀβꢀ
D
ꢀglucopyranoside 19 (55 mg, 0.26 mmol) and P(Et)3 (74 uL, 0.43 mmol) in
DMF (0.6 mL), performed as described in the general procedure of desulfurization reaction under UV
light, affording 16 as colorless oil (elution with methanol / ethyl acetate = 1:30 (v/v); 44 mg, 96% yield).
1H NMR (D2O, 400 MHz) δ = 4.18 (d, J = 7.6 Hz, 1H, Hꢀ1), 3.66ꢀ3.47 (m, 4H, Hꢀ3, Hꢀ6a, Hꢀ6b, Hꢀ5),
3.44 (s, 3H, OMe), 3.04 (t, J = 8.8 Hz, 1H, Hꢀ2), 1.86 (dd, J = 5.2 Hz, 12.8 Hz, 1H, Hꢀ4a), 1.28 (q, J =
13
12.8 Hz, 1H, Hꢀ4b) ppm; C NMR (D2O, 100 MHz) δ = 103.6, 74.9, 72.6, 70.4, 63.6, 57.1, 34.2 ppm.
HRMS (ESIꢀTOF) m/z: [M + Na]+ Calcd for C7H14O5Na 201.0739; found 201.0735.
Methyl 4ꢀdeoxyꢀαꢀ
D
ꢀxyloꢀhexopyranoside 1862: To a solution of methyl 4ꢀthioꢀαꢀ
ꢀglucopyranoside 2063 (55 mg, 0.26 mmol) and P(Et)3 (74 uL, 0.43 mmol) in
Dꢀgalactopyranoside
1765 or methyl 4ꢀthioꢀαꢀ
D
DMF (0.6 mL), performed as described in the general procedure of desulfurization reaction under UV
light, affording 18 as colorless oil (elution with methanol / ethyl acetate = 1:30 (v/v); 42 mg, 90% yield).
1H NMR (D2O, 400 MHz) δ = 4.72 (d, J = 4.0 Hz, 1H, Hꢀ1), 3.80 (m, 2H, Hꢀ2, Hꢀ3, Hꢀ5), 3.55 (dd, J =
3.2 Hz, 12.0 Hz, 1H, Hꢀ6a), 3.46 (dd, J = 6.4 Hz, 12.0 Hz, 1H, Hꢀ6b), 3.38 (dd, J = 3.6 Hz, 9.6 Hz, 1H,
Hꢀ2), 3.28 (s, 3H, OMe), 1.86 (ddd, J = 2.0 Hz, 5.2 Hz, 12.0 Hz , 1H, Hꢀ4a), 1.31 (q, J = 12.0 Hz, 1H,
Hꢀ4b) ppm; 13C NMR (D2O, 100 MHz) δ = 100.5, 74.1, 68.5, 67.5, 64.3, 54.3, 35.0 ppm. HRMS (ESIꢀ
TOF) m/z: [M + Na]+ Calcd for C7H14O5Na 201.0739; found 201.0734.
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Methyl 4ꢀthioꢀβꢀDꢀglucopyranoside 19: The deacylation of methyl 2,3,6ꢀtriꢀOꢀbenzoylꢀ4ꢀSꢀacetylꢀβꢀ
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D
ꢀglucopyranoside8 afforded 19 (CH2Cl2/MeOH = 30:1, 480 mg, 81%) as colorless oil. [α]D25 = ꢀ81.2 (c
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= 0.2 in CH3OH); H NMR (D2O, 400 MHz) δ = 4.28 (d, J = 7.6 Hz, 1H, Hꢀ1), 3.93 (dd, J = 2 Hz,12.4
Hz, 1H, Hꢀ6), 3.77 (dd, J = 5.2 Hz , 12.4 Hz, 1H, Hꢀ6), 3.46 (s, 3H, OMe), 3.44 (m, 1H, Hꢀ5), 3.31 (t, J
= 9.6 Hz, 1H, Hꢀ3), 3.14 (t, J = 8 Hz, 1H, Hꢀ2), 2.59 (t, J = 10.8 Hz, 1H, Hꢀ4) ppm; 13C NMR(CD3OD,
100 MHz) δ = 103.9, 78.0, 77.6, 74.7, 61.8, 55.8, 41.9 ppm. IR (film) v = 3360, 2921, 2851, 1633, 1410,
1207, 1063, 891, 614 cm−1. HRMS (ESIꢀTOF) m/z: [M + Na]+ Calcd for C7H14O5SNa 233.0460; found
233.0459.
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Methyl 4ꢀthioꢀαꢀD Dꢀgalactopyranoside (1.0 g, 5.15
ꢀglucopyranoside 2063: To a solution of methyl αꢀ
mmol) in dry pyridine (7 mL), benzoyl chloride (1.97 mL, 3.3 equiv.) in DCM (15 mL) was added
o
dropwise, and the mixture was stirred at ꢀ40 C for 4h. Purification of the residue by flash column
chromatography (hexane/ethyl acetate, 3:1) afforded methyl 2,3,4ꢀtriꢀOꢀbenzoylꢀαꢀ
Dꢀgalactopyranoside
as white solid (1.95 g, 75%). To a solution of methyl 2,3,4ꢀtriꢀOꢀbenzoylꢀαꢀ ꢀgalactopyranoside (1.95 g,
D
3.85 mmol) in CH2Cl2 was added pyridine (760 mg) at –30 °C. Trifluoromethanesulfonic anhydride
(2.73 g) in CH2Cl2 (2 mL) was added dropwise, and the mixture was stirred while allowing to warm
from –30 °C to 10 °C over 2 h. The resulting mixture was subsequently diluted with CH2Cl2 and washed
with 1M HCl, aqueous NaHCO3, water, and brine. The organic phase was dried with Mg2SO4 and
concentrated in vacuo at low temperature. The residue was solved in dry DMF (5.0 mL) which was used
directly in the next step. KSAc (1.5 equiv.) was added to the solution. After stirring at room temperature
for 24 h under nitrogen atmosphere, the mixture was diluted by ethyl acetate, and washed with brine.
The organic phase was dried with MgSO4 and concentrated in vacuum. Purification of the residue by
flash column chromatography (ethyl acetate/petrol, 1:4ꢀ1:7) afforded methyl 2,3,6ꢀtriꢀOꢀbenzoylꢀ4ꢀSꢀ
1
acetylꢀαꢀ
D
ꢀglucopyranoside63 (1.59 g, 73%) as colorless oil. H NMR (400 MHz, CDCl3) δ = 8.17ꢀ7.90
(m, 6H, Ph), 7.65ꢀ7.33 (m, 9H, Ph), 5.94 (dd, J = 11.1 Hz, 9.6 Hz, 1H, Hꢀ3), 5.30ꢀ5.20 (m, 2H, Hꢀ1, Hꢀ
2), 4.65 (dd, J = 2.1 Hz, 12.1 Hz, 1H, Hꢀ6a), 4.56 (dd, J = 5.1 Hz, 12.1 Hz, 1H, Hꢀ6b), 3.95 (ddd, J =
2.1 Hz, 5.1 Hz, 11.1 Hz, 1H, Hꢀ5), 4.18 (t, J = 11.1 Hz, 1H, Hꢀ4), 3.43 (s, 3H, OMe), 2.21 (s, 3H, SAc)
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ppm; C NMR (100 MHz, CDCl3) δ =192.5, 166.3, 165.8, 165.7, 133.3, 133.2, 133.1, 129.9, 129.8,
129.7, 129.2, 129.1, 128.4, 128.4, 128.3, 97.2, 77.2, 73.1, 69.3, 68.6, 63.8 ppm. HRMS (ESIꢀTOF) m/z:
[M + Na]+ Calcd for C30H28O9SNa 587.1352; found 587.1335. The deacylation of methyl 2,3,6ꢀtriꢀOꢀ
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benzoylꢀ4ꢀSꢀacetylꢀαꢀ
D
ꢀglucopyranoside afforded methyl 4ꢀthioꢀαꢀDꢀglucopyranside 20 (CH2Cl2/MeOH
9
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= 30:1, 480 mg, 81%) as colorless oil. H NMR (D2O, 400 MHz) δ = 4.76 (d, J = 2.8 Hz, 1H, Hꢀ1),
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3.83 (d, J = 3.6 Hz, 2H, Hꢀ6a,Hꢀ6b), 3.62 (ddd, J = 10.4, 3.6 Hz,1H, Hꢀ5), 3.46 (m, 2H, Hꢀ2, Hꢀ3),
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3.31(s, 3H, OMe), 2.61 (t, J = 10.4 Hz, 1H, Hꢀ4) ppm; C NMR(CD3OD, 100 MHz) δ = 100.1, 74.2,
73.7, 73.1, 61.8, 54.2, 42.1 ppm. HRMS (ESIꢀTOF) m/z: [M + Na]+ Calcd for C7H14O5SNa 233.0460;
found 233.0457.
Methyl 3ꢀthioꢀ4,6ꢀO-benzylidene-βꢀ
D
ꢀallopyranoside 21: The deacylation of methyl 3ꢀSꢀacetylꢀ4,6ꢀOꢀ
benzylideneꢀβꢀ
D
ꢀallopyranoside38 afforded 21 (552 mg, 87% ) as colorless oil. [α]D25 = ꢀ128.5 (c = 0.15
1
in CHCl3); H NMR (400 MHz, CDCl3) δ = 7.54ꢀ7.33 (m, 5H, Ph), 5.58 (s, 1H, CH), 4.73 (d, J = 7.6
Hz, 1H, Hꢀ1), 4.35 (dd, J = 10.4, 5.2 Hz, 1H, Hꢀ3), 4.17 (m, 1H, Hꢀ4), 4.11 (m, 1H, Hꢀ6a), 3.83 (dd, 1H,
13
Hꢀ5), 3.80ꢀ3.70 (m, 2H, Hꢀ6, Hꢀ2), 3.57 (s, 3H, OMe), 2.61 (s, 1H, OH), 2.03 (s, 1H, SH) ppm; C
NMR (CDCl3, 100 MHz) δ = 137.0, 129.3, 128.4, 126.3, 101.7, 101.5, 77.8, 70.4, 68.9, 63.9, 57.4, 43.2
ppm. IR (film) v = 3361, 2924, 2853, 1660, 1463, 1269, 1090, 851, 714 cm−1. HRMS (ESIꢀTOF) m/z:
[M + Na]+ Calcd for C14H18O5SNa 321.0733; found 321.0739.
Methyl 3ꢀdeoxyꢀ4,6ꢀO-benzylidene-βꢀDꢀallopyranoside 22: To a solution of methyl 3ꢀthioꢀ4,6ꢀOꢀ
benzylideneꢀβꢀ ꢀallopyranoside 21 (70 mg, 0.24 mmol) and P(Et)3 (65 uL, 0.38 mmol) in DMF (0.6
D
mL), performed as described in the general procedure of desulfurization reaction under UV light,
affording 22 as colorless oil (elution with methanol / ethyl acetate = 1:30 (v/v); 42 mg, 90% yield).
[α]D25 = ꢀ54.7 (c = 0.15 in CHCl3); 1H NMR (400 MHz, CDCl3) δ = 7.54ꢀ7.33 (m, 5H, Ph), 5.53 (s, 1H,
CH), 4.34 (dd, J = 4.8, 10.4 Hz, 1H, Hꢀ5), 4.25 (d, J = 7.6 Hz, 1H, Hꢀ1), 3.77 (t, J = 10.0 Hz, 1H, Hꢀ6a),
3.63ꢀ3.56 (m, 2H, Hꢀ2, Hꢀ4), 3.58 (s, 3H, OMe), 3.46 (m, 1H, Hꢀ6b), 2.45 (dt, J = 4.8, 12.0 Hz, 1H, Hꢀ
13
3a), 1.75 (q, J = 11.6, 1H, Hꢀ3b) ppm; C NMR (CDCl3, 100 MHz) δ = 137.3, 129.1, 128.4, 126.2,
106.4, 101.8, 76.2, 70.6, 69.2, 69.1, 57.3, 35.0 ppm. IR (film) v = 3371, 2925, 2852, 1612, 1432, 1216,
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1081, 908, 696 cm−1. HRMS (ESIꢀTOF) m/z: [M + Na]+ Calcd for C14H18O5Na 289.1052; found
289.1039.
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Methyl 2,4ꢀdiꢀdeoxyꢀβꢀDꢀthreo-Hexopyranoside 24: To a solution of methyl 2,4ꢀdiꢀthioꢀβꢀDꢀ
mannopyranoside 2336 (102 mg, 0.46 mmol) and P(Et)3 (252 uL, 1.48 mmol) in DMF(1 mL), performed
as described in the general procedure of desulfurization reaction under UV light, affording 24 as
colorless oil (elution with methanol / ethyl acetate = 1:50 (v/v); 41 mg, 55% yield). [α]D25 = +22.5 (c =
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2.0 in CH3OH); H NMR (400 MHz, D2O) δ = 4.40 (dd, J = 2.0, 9.2 Hz, 1H, Hꢀ1), 3.84 (m, 1H, Hꢀ3),
3.61ꢀ3.44 (m, 3H, Hꢀ5, Hꢀ6a, Hꢀ6b), 3.40 (s, 3H, OMe), 2.08 (ddd, J = 12.0 Hz, 1H, Hꢀ2a), 1.78 (d, J =
12.4 Hz, 1H, Hꢀ4a), 1.19ꢀ0.96 (m, 2H, Hꢀ2b, Hꢀ4b) ppm; 13C NMR (100 MHz, CD3OD) δ = 101.3, 72.9,
65.9, 64.5, 55.3, 40.4, 36.2 ppm. IR (film) v = 3388, 2923, 1645, 1460, 1383, 1175, 1029, 669 cm−1.
HRMS (ESIꢀTOF) m/z: [M + Na]+ Calcd for C7H14O4Na 185.0790; found 185.0786.
Methyl 2,4ꢀdiꢀdeoxyꢀαꢀD Dꢀ
ꢀthreoꢀHexopyranoside 2664: To a solution of methyl 2,4ꢀdiꢀthioꢀαꢀ
mannopyranoside 2536 (110 mg, 0.49 mmol) and P(Et)3 (265 uL, 1.56 mmol) in DMF (1 mL), performed
as described in the general procedure of desulfurization reaction under UV light, affording 26 as
colorless oil (elution with methanol / ethyl acetate = 1:50 (v/v); 46 mg, 58% yield). [α]D25 = +166.8 (c =
1
1.2 in CH3OH); H NMR (400 MHz, D2O) δ = 4.89 (d, J = 3.6 Hz, 1H, Hꢀ1), 3.98 (m, 1H, Hꢀ3), 3.77
(m, 1H, Hꢀ5), 3.58 (dd, J = 3.2 Hz, 12.0 Hz, 1H, Hꢀ6a), 3.50 (dd, J = 6.4 Hz, 12.0 Hz, 1H, Hꢀ6b), 3.25
(s, 3H, OMe), 1.98 (m, 1H, Hꢀ2a), 1.84 (m, 1H, Hꢀ4a), 1.45 (ddd, J = 3.6 Hz, 11.6 Hz, 15.2 Hz , 1H, Hꢀ
13
2b), 1.21 (q, J = 11.6 Hz, 1H, Hꢀ4b) ppm; C NMR (100 MHz, D2O) δ = 99.0, 68.9, 64.2, 62.9, 54.3,
37.5, 35.2 ppm. IR (film) v = 3393, 2923, 1630, 1451, 1383, 1166, 1083, 669 cm−1. HRMS (ESIꢀTOF)
m/z: [M + Na]+ Calcd for C7H14O4Na 185.0790; found 185.0789.
1,5ꢀanhydroꢀ2,3,4,6ꢀtetraꢀOꢀbenzylꢀ
D
ꢀglucitol 2866: To a solution of 2,3,4,6ꢀtetraꢀOꢀbenzylꢀ1ꢀthioꢀ
α/βꢀ ꢀglucopyranose 27 (100 mg, 0.18 mmol) and P(Bu)3 (90 uL, 0.35 mmol) in DMF(0.6 mL),
D
performed as described in the general procedure of desulfurization reaction under UV light, affording 28
as colorless oil (elution with ethyl acetate/petroleum ether = 1:8 (v/v); 83 mg, 89% yield). 1H NMR (400
MHz, CDCl3) δ = 3.23ꢀ3.27 (m, 1H, Hꢀ2), 3.42 (ddd, J = 9.5 Hz, 4.2 Hz, 2.2 Hz, 1H, Hꢀ5), 3.60 (t, J =
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9.5 Hz, 1H, Hꢀ4), 3.65ꢀ3.70 (m, 3H, Hꢀ1a, Hꢀ3, Hꢀ6), 3.72 (dd, J = 10.5 Hz, 2.2 Hz, 1H, Hꢀ6), 4.08 (dd,
J = 11.3 Hz, 4.7 Hz, 1H, Hꢀ1b), 4.53, 4.87 (AB, JAB = 10.7 Hz, 2H, CH2Ph), 4.55, 4.63 (AB, JAB = 12.1
Hz, 2H, CH2Ph), 4.70, 4.76 (AB, JAB = 11.5 Hz, 2H, CH2Ph), 4.89, 5.01 (AB , JAB = 11.0 Hz, 2H,
CH2Ph), 7.37 – 7.11(m, 20H, ArꢀH) ppm.
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(Methyl 2ꢀthioꢀαꢀmannopyranosyl)ꢀ(Methyl 2ꢀthioꢀαꢀmannopyranosyl) disulfide 31: A solution of
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methyl 2ꢀthioꢀαꢀDꢀmannopyranoside (207 mg, 0.99 mmol) in CH3OH (3 mL) was stirred at room
temperature with the air oxidation until TLC indicated complete consumption of the starting material,
purified by silica gel chromatography (CH3OH:EtOAc 20:1) to give 31 (200 mg, 97%) as colorless oil.
25
1
[α]D = ꢀ87.1 (c = 1.4 in CH3OH); H NMR (400 MHz, D2O) δ = 5.12 (s, 1H, Hꢀ1), 4.13 (dd, J = 9.5,
5.0 Hz, 1H, Hꢀ3), 3.86 (d, J = 12.4 Hz, 1H, Hꢀ6a), 3.74 (dd, J = 12.4, 5.7 Hz, 1H, Hꢀ6b), 3.69 – 3.59 (m,
1H, Hꢀ5), 3.52 (t, J = 9.5 Hz, 1H, Hꢀ4), 3.49 (d, J = 5.0 Hz, 1H, Hꢀ2), 3.42 (s, 3H, OMe) ppm; 13C NMR
(100 MHz, D2O) δ = 100.7, 72.8, 69.3, 67.3, 60.6, 59.6, 54.9 ppm. IR (film) v = 3364, 2923, 2852, 1659,
1413, 1253, 1120, 960, 610 cm−1. HRMS (ESIꢀTOF) m/z: [M + Na]+ Calcd for C14H26O10S2Na
441.0865; found 441.0875.
Spectroscopic data of known products were in accordance with those reported in the literature.
Acknowledgments
This study was supported by the National Nature Science Foundation of China (Nos. 21272083). The
authors are also grateful to the staffs in the Analytical and Test Center of School of Chemistry &
Chemical Engineering at HUST for support with the NMR instruments.
Supporting Information Available: Figure S1ꢀ8, 1H NMRꢀ and 13C NMRꢀspectra of compounds 1 ꢀ 30,
Computational Methods and cartesian coordinates, and total energies. This material is available free of
charge via the Internet at http://pubs.acs.org.
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