Regioselective mono and multiple alkylation of diols and polyols catalyzed by organotin and its applications on the synthesis of value-added carbohydrate intermediates

Article abstract of DOI:10.1016/j.tet.2016.04.076

A catalytic amount of dibutyltin dichloride was used to develop regioselective alkylation of diols and multiple alkylation of polyols. Alkyl groups, including allyl, alkynyl and long-chain alkyl groups, were successfully introduced to one or two hydroxyl

Full text of DOI:10.1016/j.tet.2016.04.076

Tetrahedron 72 (2016) 3490e3499
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Regioselective mono and multiple alkylation of diols and polyols
catalyzed by organotin and its applications on the synthesis of
value-added carbohydrate intermediates
,
Hengfu Xu a, Bo Ren b, Wei Zhao a, Xiaoting Xin a, Yuchao Lu a, Yuxin Pei a, Hai Dong b
*
,
,
Zhichao Pei a
*
a College of Science, Northwest A&F University, Yangling, 712100, Shaanxi, PR China
b Key Laboratory of Material Chemistry for Energy Conversion and Storage, Ministry of Education, Huazhong University of Science & Technology, Luoyu
Road 1037, Wuhan, 430074, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
A catalytic amount of dibutyltin dichloride was used to develop regioselective alkylation of diols and
multiple alkylation of polyols. Alkyl groups, including allyl, alkynyl and long-chain alkyl groups, were
successfully introduced to one or two hydroxyl groups of carbohydrate and nonsugar substrates. In most
cases, excellent isolation yields were obtained. The alkynylated carbohydrates may be used to synthesize
oligosaccharide mimics at a high efficiency via click reaction. The carbohydrates with long-chain alkyl
groups may serve as surfactants, which were further demonstrated by experiments in this study.
Ó 2016 Elsevier Ltd. All rights reserved.
Received 29 January 2016
Received in revised form 25 April 2016
Accepted 27 April 2016
Available online 28 April 2016
Keywords:
Alkylation
Organotin
Carbohydrates
Catalysis
Regioselectivity
1. Introduction
Regioselective protection of carbohydrates is often indispens-
able for the preparation of value-added intermediates and building
blocks for oligosaccharide synthesis.1e5 The method using stoi-
chiometric amounts of organotin reagents used to be the most
popular regioselective protection method.6,7 However, the orga-
notin compounds have to be either minimized in its usage to
a catalytic amount,8e12 or totally abandoned13e19 now due to their
potential inherent toxicity.20,21 The regioselective alkylation of
carbohydrates and polyols using a catalytic amount of organotin
have been reported by two other groups22,23 as well as our group24
recently. Our developed method used 0.1 equiv of TBAB (tetrabu-
tylammonium bromide) and 0.1 equiv of organotin as catalyst, and
used excess amount of potassium carbonate to deprotonate the
hydroxyl group and push through the reaction (Fig. 1a). We mainly
used an one-pot method where first 0.1 equiv of dibutyltin oxide
formed dibutylstannylene acetal with two vicinal OH of the sub-
strates, then the concentrated dibutylstannylene acetal reacted
with benzyl bromide to produce the final products in the assistance
* Corresponding authors. E-mail addresses: hdong@mail.hust.edu.cn (H. Dong),
peizc@nwafu.edu.cn (Z. Pei).
Fig. 1. Comparison of three previous reported methods.
http://dx.doi.org/10.1016/j.tet.2016.04.076
0040-4020/Ó 2016 Elsevier Ltd. All rights reserved.

H. Xu et al. / Tetrahedron 72 (2016) 3490e3499
3491
Table 1
of 0.1 equiv of TBAB and 1.1 equiv of K2CO3, indicating the key role
Regioselective mono-alkylation of diols and polyolsa
of dibutylstannylene acetal in the reaction mechanism. In Alfonso
et al.’s work,22 0.1 equiv of dibutyltin oxide was also used, but in
conjuncture with 0.3 equiv of TBAB, excess amount of DIPEA (dii-
sopropylethyl amine) and alkylation reagents (Fig. 1b). Further-
more, they expanded their method on allylation and multiple
benzylation. However, in most cases, only intermediate yields were
obtained in this solvent free condition used by them.
Entry
Substrate
Product
Yield (%)b
1
2
R¼Allyl
1a
88
86
R¼Propargyl 1b
Just recently, Vishwakarma group reported a method using
0.1 equiv of dimethyltin dichloride as catalyst with the assistance of
an excess amount of silver oxide (Ag2O) (Fig. 1c).23 Though their
reported reaction condition was more mild (room temperature),
the reaction required longer reaction time (24 h) and might be only
applicable in a limited scope of substrates. In this study, the effi-
ciency of our one-step method, using 0.1 equiv of dibutyltin
dichloride as the catalyst, was fully demonstrated and this method
was further expanded to regioselective mono-alkylation using
various alkylation reagents and to regioselective multiple alkyl-
ation (Fig. 2). The regioselective alkylation mechanism should be
the same as we proposed in previous studies.24 In most cases, better
isolation yields were obtained for both regioselective mono-
alkylation and regioselective multiple alkylation of substrates.
The selective multiple protections are of particularly importance
since two or more hydroxyl groups in polyols can be protected in
a single-step process.25e29 The regioselective introduction of alkyl,
allyl or alkynyl groups may supply useful value-added in-
termediates, which in turn can be applied in producing novel car-
bohydrate materials such as surfactants, hydrophilic polymers and
so on.30e32 Carbohydrates containing multiple alkynyl groups have
been successfully used to synthesize oligosaccharide mimics via
click reaction.33,34 In this study, we also give examples of applica-
tion in these fields and our method showed a higher efficiency
compared to previously reported methods.
3
4
R¼Allyl
2a
83
85
R¼Propargyl 2b
5
6
R¼Allyl
3a
82
86
R¼Propargyl 3b
7
8
R¼Allyl
4a
86
88
R¼Propargyl 4b
9
10
R¼Allyl
5a
91
95
R¼Propargyl 5b
11
12
R¼Allyl
6a
85
87
R¼Propargyl 6b
13
14
R¼Allyl
7a
87
89
R¼Propargyl 7b
15
16
R¼Allyl
8a
85
89
R¼Propargyl 8b
17
18
R¼Allyl
9a
75
78
R¼Propargyl 9b
19
20
R¼Allyl
10a 81
R¼Propargyl 10b 85
Fig. 2. Regioselective mono and multiple alkylation catalyzed by Bu2SnCl2.
2. Results and discussion
21
22
R¼Allyl
11a 89
R¼Propargyl 11b 90
The allylation and alkynylation were first tested with substrates
containing a cis-diol moiety, compounds 1e13, and substrates
containing a 1,2-diol, compounds 14 and 15 (Table 1). These sub-
strates were treated with 2.0 equiv of allyl bromide or alkynyl
bromide in the presence of 0.1 equiv of dibutyltin dichloride,
0.1 equiv of tetrabutylammonium bromide and 1.5 equiv of K2CO3
in a mixed solvent (MeCN:DMF, 10:1) at 80 ꢀC for 3 h. In most of the
substrates, the equatorial hydroxyl group adjacent to an axial hy-
droxyl group or the primary hydroxyl group of 1,2-diol was selec-
tively alkylated in isolated yields of 75e95%. Selective protection of
thioglycosides was extremely important since thioglycosides acting
as significant glycosyl donors are widely used in glycosylation and
oligosaccharide syntheses. The allylation and alkynylation of 9, an
example of thioglycosides, gave 75e78% yields of 9ae9b, re-
spectively, indicating that this method can be used for the
23
24
R¼Allyl
12a 70
R¼Propargyl 12b 65
25
26
R¼Allyl
13a 89
R¼Propargyl 13b 90
(continued on next page)

3492
H. Xu et al. / Tetrahedron 72 (2016) 3490e3499
the substrate. In light of the previous report,24 it is known that the
Table 1 (continued )
equatorial hydroxyl group adjacent to an axial hydroxyl group or
the primary hydroxyl group of 1,2-diol showed higher reactivity
than other hydroxyl groups. Thus, it is expected that 3- and 6-
postions of compound 2 would be alkylated in a one-pot reaction.
In order to observe the reaction process, the tests were performed
in two steps. In the first step, the 3-position of compound 2 was
regioselectively benzylated under the standard conditions showed
in Table 1. With the addition of more BnBr and bases into the re-
action mixture in the following step, 6-position of compound 2 was
further selectively benzylated (Table 2). Under ‘standard’ condi-
tions, the 3- and 6-positions of compound 2 were selectively ben-
zylated in the one-pot reaction and the NMR yield of target product
21 was obtained up to 90% (Entry 1 in Table 2). However, compound
21 was only obtained in 42e50% yield when K2CO3, triethylamine
(TEA) and N,N-Diisopropylethylamine (DIPEA) were used instead of
NaOH in the second step even when the reaction was prolonged for
another 16 h (Entries 2e4 in Table 2). The increase of the amount of
BnBr and the higher reaction temperature could not increase the
yields of 21 by much (Entries 5 and 6 in Table 2). The reduced
amount of NaOH and BnBr led to lower yield of compound 21
correspondingly (Entry 7 in Table 2). We also tried to perform the
reaction in one step where compound 2 reacted with 3.0 equiv of
BnBr in the presence of 3.0 equiv of NaOH under the dibutyltin
dichloride catalyzed conditions. However, compound 21 was only
obtained in 30% yield due to the poor selectivity (Entry 8 in Table 2).
Entry
Substrate
Product
Yield (%)b
27
28
R¼Allyl
14a 96
R¼Propargyl 14b 94
29
30
R¼Allyl
15a 86
R¼Propargyl 15b 84
a
Conditions: substrates (100 mg), Bu2SnCl2 (0.1 equiv), K2CO3 (1.5 equiv), TBAB
(0.1 equiv), RBr (2.0 equiv), MeCN:DMF (10:1) (2 mL), 80 ꢀC, 3 h.
b
Isolated yields.
modification of thioglycoside building blocks35e39 (Entries 17e18
in Table 1). In addition, the allylation and alkynylation of methyl 2-
N-acetyl-a-D-galactosamine 11 was also tested, giving 89e90%
yields of 11ae11b (Entries 21e22 in Table 1).
The method was further used to regioselectively install a long-
chain alkyl group onto polyol substrates, where the long-chain al-
kyl group can serve as a hydrophobic end and the polyol can serve
as a hydrophilic head (Fig. 3). Thereafter, various potent surfactants
may be efficiently synthesized by using this regioselective mono-
alkylation method.
Table 2
Regioselective multiple alkylation of Methyl a-D
-galactosidea
Entry
Variation from the ‘standard’ conditions in second step
Yield (%)b
1
2
3
4
5
6
7
8c
None
90
42
50
45
45
58
75
30
K2CO3 intead of NaOH, 16 h
TEA instead of NaOH, 16 h
DIPEA instead of NaOH, 16 h
K2CO3 intead of NaOH, 2.0 equiv, BnBr,16 h
K2CO3 intead of NaOH, 2.0 equiv, BnBr, reflux, 16 h
1.0 equiv BnBr, 1.0 equiv, NaOH
NaOH only in all reaction protocol
Fig. 3. Alkylation of methyl a/b
-D-galactosidesa. [a] Conditions: substrates (100 mg),
Bu2SnCl2 (0.1 equiv), K2CO3 (1.5 equiv), TBAB (0.1 equiv), RBr (2.0 equiv), MeCN:DMF
(10:1) (2 mL), reflux, 10 h [b] Water. [c] Aqueous solution of compound 20.
a
Conditions: 1) substrates (100 mg), Bu2SnCl2 (0.1 equiv), K2CO3 (1.5 equiv), TBAB
(0.1 equiv), BnBr (2.0 equiv), MeCN:DMF (10:1) (2 mL), 80 ꢀC, 3 h. 2) NaOH
(1.5 equiv) and additional BnBr (1.5 equiv), 80 ꢀC, 2 h.
b
NMR yields.
In addition, it has been reported that the presence of long hy-
drophobic alkyl chains in some carbohydrates might be involved in
certain inhibition processes.40e42 The reported synthesis methods
relied on the use of stoichiometric amount of dibutyltin oxide.43,44
c
Conditions: substrates (100 mg), Bu2SnCl2 (0.1 equiv), NaOH (3.0 equiv), TBAB
(0.1 equiv), BnBr (3.0 equiv), MeCN:DMF (10:1) (2 mL), 80 ꢀC, 16 h.
In this method, methyl a/b-D-galactosides as the hydrophilic end
With the optimized conditions, the method was further applied
for more substrates and various alkylation reagents (Table 3).
Good results were obtained for galacto-compounds when various
alkylation reagents were used. The more meaningful results are
that the 3- and 6-position of galacto-substrates were occupied by
different alkyl groups. For example, by using methoxylbenzyl
bromide instead of benzyl bromide in the second step, compound
25, 30, 34 and 38 where 3-positions protected by benzyl groups
and 6-positions protected by p-methoxyl benzyl groups, could be
obtained in 73e79% yields in this one-pot reaction. It is also im-
portant for the development of potent surfactants that 3- and 6-
positions of methyl galactosides 2 and 3 were installed long-
chain alkyl groups though 24 and 29 were obtained in medium
yields (Entries 4 and 9 in Table 3). The results in entries 13e16
indicated that thio-glycosides could withstand the conditions in
were tested to be installed with various long-chain alkyl groups as
the hydrophobic end. Due to the relatively low reactivity of alkyl
bromide reagents, reaction temperature had to be increased by
reflux. Consequently, potent surfactants 16e20 were obtained in
60e68% yields. More importantly, results showed the installation of
1,4-dibromobutane and 1,6-dibromohexane. This is significant be-
cause products with a remainder bromine on the alkyl end could be
further modified by substituting the bromine. Compound 20 was
further proven as an amphiphile, as shown in Fig. 3c, an aqueous
solution of 20 exhibited a clear Tyndall effect, indicating the exis-
tence of abundant nanoparticles. And the critical micelle concen-
tration (CMC) of 20 was determined to be approximately 72 mM by
water surface tension method (Fig. S1).
The method was further tested in regioselective multiple al-
kylation. First, the reaction conditions were optimized on the basis
the method. However, poor results were obtained when methyl
a-
of mono-alkylation where methyl a-D-galactoside 2 was chosen as
D-mannopyranoside 1 was tested using the method (Entries 19e21

H. Xu et al. / Tetrahedron 72 (2016) 3490e3499
3493
Table 3
oligosaccharide mimics toward two mannose specific lectins were
found to follow identical trends to those observed for natural oli-
gosaccharide counterparts. However, this method for installing
alkynyl on the 3- and 6- positions of mannosides requires at least
four steps. Our method supplies a more efficient approach to syn-
thesize these types of oligosaccharide mimics. For example, triazole
disaccharide 43 was isolated in 81% yield through the click reaction
of compound 10 and 3-position alkynylated compound 3b, and
triazole trisaccharide 44 was obtained in 80% yield through the
click reaction of 10 and 3,6-positions alkynylated compound 28
(Fig. 4).
Regioselective multiple alkylation of carbohydratesa
Entry
Substrate
Product
Yield (%)b
1
2
3
R1¼R2¼Bn
21 73
R1¼R2¼Allyl
22 74
23 70
24 55
25 74
R1¼R2¼Propargyl
R1¼R2¼Hexyl
R1¼Bn, R2¼PMB
4
5c
6
7
8
R1¼R2¼Bn
26 76
27 70
28 78
29 60
30 75
R1¼R2¼Allyl
R1¼R2¼Propargyl
R1¼R2¼Hexyl
R1¼Bn, R2¼PMB
9
10c
11
12
13
14c
R1¼R2¼Bn
31 86
32 88
33 81
34 79
R1¼R2¼Allyl
R1¼R2¼Propargyl
R1¼Bn, R2¼PMB
15
16
17
18c
R1¼R2¼Bn
35 79
36 71
37 68
38 73
Fig. 4. Synthesis of oligosaccharide mimics by regioselective alkynylation and click
reaction. Conditions: a compound 3b (100 mg), compound 10 (1.1 equiv), CuSO4$5H2O
(0.1 equiv), NaVc (0.25 equiv), DCM/H2O (1:1) (4 mL), rt, 24 h. Yield 81%. b compound
28 (100 mg), compound 10 (2.2 equiv), CuSO4$5H2O (0.2 equiv), NaVc (0.5 equiv),
DCM/H2O (1:1) (4 mL), rt, 24 h. Yield 80%.
R1¼R2¼Allyl
R1¼R2¼Propargyl
R1¼Bn, R2¼PMB
19
R2¼Bn, R1¼H
R1¼Bn, R2¼H
39a 39
39b 31
3. Conclusions
In conclusion, our method, using dibutyltin dichloride as cata-
lyst, is superior for regioselective mono- and multiple alkylations of
diols and polyols. High isolation yields were obtained for alkyny-
lation and allylation of numerous carbohydrate derivatives and
non-sugar diols. Medium yields were obtained for multiple alkyl-
ations of free galacto-type carbohydrates. The method is also con-
venient for installing a long alkyl chain on carbohydrate derivatives,
which may serve as surfactant and could potentially have biological
applications. The multiple alkynylated carbohydrates can be used
to synthesize oligosaccharide mimics with high efficiency via click
reaction.
R2¼Allyl, R1¼H
R1¼Allyl, R2¼H
40a 46
40b 20
20
21
1
1
R2¼Propargyl, R1¼H 41a 29
R1¼Propargyl, R2¼H 41b 34
R2¼Bn, R1¼H
R1¼Bn, R2¼H
39a 43
39b 33
22d
4. Experimental section
4.1. General information
a
Conditions: 1) substrates (100 mg), Bu2SnCl2 (0.1 equiv), TBAB (0.1 equiv),
K2CO3 (1.5 equiv), RBr (2.0 equiv), MeCN/DMF (10:1) (2 mL), 80 ꢀC, 3 h. 2) NaOH
(1.5 equiv) and additional RBr (1.5 equiv), 80 ꢀC, 3 h.
b
All commercially available starting materials and solvents were
of reagent grade and dried prior to use. Chemical reactions were
monitored with thin-layer chromatography using precoated silica
gel 60 (0.25 mm thickness) plates. Flash column chromatography
was performed on silica gel 60 (0.040e0.063 mm). NMR spectra
were recorded with a 500 MHz instrument (500 MHz for 1H and
125 MHz for 13C) at 298K in DMSO-d6, D2O, CDCl3, using the re-
Isolated yields.
c
Conditions: 1) substrates (100 mg), Bu2SnCl2 (0.1 equiv), K2CO3 (1.5 equiv),
TBAB (0.1 equiv), BnBr (2.0 equiv), MeCN:DMF (10:1) (2 mL), 80 ꢀC, 3 h. 2) NaOH
(1.5 equiv) and PMBBr (1.5 equiv), 80 ꢀC, 2 h.
d
Conditions: substrates (100 mg), Bu2SnCl2 (0.1 equiv), TBAB (0.1 equiv), NaOH
(1.5 equiv) and BnBr (1.5 equiv), 80 ꢀC, 3 h.
sidual signals from DMSO-d6 (1H:
d
¼2.50 ppm, 13C:
¼39.52 ppm),
d
in Table 3). The formation of 2,3-alkylated products always ac-
companied the formation of 3,6-alkylated products. The reason is
likely due to the higher acidity of 2-OH of mannoside 1. Thus,
D2O (1H:
d
¼3.34 ppm) and CDCl3 (1H:
d
¼7.27 ppm, 13C:
d¼77.16 ppm) as internal standard.
when methyl 3-OBn-a-D-mannopyranoside 39, as the starting
material, was tested with conditions in step 2, a similar result was
obtained (Entry 22 in Table 3).
4.2. General procedure for selective monoalkylation of sub-
strates containing a cis-diol
A method has been reported for the synthesis of a new family of
high-mannose oligosaccharide mimics in which some inner man-
nopyranosyl units are replaced by triazole rings through click re-
action.33,34 The binding affinities of the new ‘click’ high-mannose
Diol or polyol (100 mg) and dibutyltin dichloride (0.1 equiv)
were added in dry MeCN/DMF (10:1) (2 mL), in the presence of
TBAB (0.1 equiv), K2CO3 (1.5 equiv) and alkylation reagent

3494
H. Xu et al. / Tetrahedron 72 (2016) 3490e3499
(2.0 equiv). The reaction proceeded at 80 ꢀC for 3 h. After the re-
moval of the solvents, the residue was purified by column chro-
matography to give the desired pure product.
J¼15.8, 2.5 Hz, 1H), 4.36 (dd, J¼15.8, 2.4 Hz, 1H), 4.32e4.25 (m, 1H),
4.17 (dd, J¼3.6, 1.5 Hz, 1H), 4.10e4.05 (m, 1H), 3.98 (dd, J¼9.6,
3.4 Hz, 1H), 3.89e3.83 (m, 2H), 3.41 (s, 3H), 2.62 (s, 1H), 2.48 (t,
J¼2.4 Hz, 1H). 13C NMR (125 MHz, CDCl3):
d 137.58, 129.12, 128.37,
4.3. General procedure for selective multiple alkylation of
substrates containing a cis-diol
126.24,101.87, 101.29, 80.01, 78.92, 75.69, 74.93, 70.33, 69.04, 63.32,
58.88, 55.15. HRMS m/z calcd for C17H20O6 [MþNa]þ: 343.1152.
Found 343.1153.
4.3.1. Method a. Diol or polyol (100 mg) and dibutyltin dichloride
(0.1 equiv) were added in dry MeCN/DMF (10:1) (2 mL), in the
presence of TBAB (0.1 equiv), K2CO3 (1.5 equiv) and alkylation re-
agent (2.0 equiv). The reaction proceeded at 80 ꢀC for 3 h. There-
after, NaOH (1.5 equiv) and additional alkylation reagent (1.5 equiv)
were added and the reaction proceeded at 80 ꢀC for another 2 h.
After the removal of the solvents, the residue was purified by col-
umn chromatography to give the desired pure product.
4.8. Methyl-6-(tert-butyldimethylsilyloxy)-3-O-allyl-a-D-
mannopyranoside (6a)
Colorless oil, yield: 85%, Rf¼0.63 (ethyl acetate/petroleum
ether¼1:1). 1H NMR (500 MHz, CDCl3):
d 6.01e5.93 (m, 1H), 5.33
(dq, J¼17.2, 1.6 Hz, 1H), 5.22 (dq, J¼10.4,1.3 Hz,1H), 4.75 (d, J¼1.6 Hz,
1H), 4.23e4.14 (m, 2H), 3.98 (dt, J¼3.8, 2.0 Hz, 1H), 3.91e3.86 (m,
2H), 3.84 (dd, J¼9.4, 1.6 Hz, 1H), 3.63e3.58 (m, 2H), 3.38 (s, 3H), 3.02
4.3.2. Method b. Diol or polyol (100 mg) and dibutyltin dichloride
(0.1 equiv) were added in dry MeCN/DMF (10:1) (2 mL), in the
presence of TBAB (0.1 equiv), K2CO3 (1.5 equiv) and alkylation re-
agent A (2.0 equiv). After the reaction proceeded at 80 ꢀC for 3 h,
NaOH (1.5 equiv) and another alkylation reagent B (2.0 equiv) were
added. The reaction proceeded at 80 ꢀC for another 2 h. After the
removal of the solvents, the residue was purified by column chro-
matography to give the desired pure product.
(d, J¼1.7 Hz, 1H), 2.40 (d, J¼2.6 Hz, 1H), 0.91 (s, 9H), 0.10 (s, 6H). 13
C
NMR (125 MHz, CDCl3):
d 134.66, 117.91, 100.53, 79.03, 71.03, 70.86,
69.35, 67.92, 64.99, 55.02, 26.02, 18.41, ꢁ5.33. HRMS m/z calcd for
C
16H32O6Si [MþNa]þ: 371.1860. Found 371.1865.
4.9. Methyl-6-(tert-butyldimethylsilyloxy)-3-O-propargyl-
a-
D-mannopyranoside (6b)
Colorless oil, yield: 87%, Rf¼0.61 (ethyl acetate/petroleum
4.4. Methyl-3-O-propargyl-
a
-
D
-mannopyranoside (1b)
ether¼1:1). 1H NMR (500 MHz, CDCl3):
d
4.75 (d, J¼1.7 Hz, 1H),
4.43e4.32 (m, 2H), 4.08 (td, J¼3.2, 1.7 Hz, 1H), 3.92e3.85 (m, 3H),
3.76 (dd, J¼9.1, 3.4 Hz, 1H), 3.63 (dt, J¼9.3, 5.4 Hz, 1H), 3.39 (s, 3H),
3.06 (d, J¼1.7 Hz, 1H), 2.50 (t, J¼2.4 Hz, 1H), 2.34 (t, J¼2.6 Hz, 1H),
Colorless oil; yield: 86%, Rf¼0.31 (ethyl acetate), 1H NMR
(500 MHz, CDCl3):
d
4.77 (d, J¼1.8 Hz, 1H), 4.36 (d, J¼2.4 Hz, 2H),
4.09 (dd, J¼3.2, 1.8 Hz, 1H), 4.00 (t, J¼9.7 Hz, 1H), 3.94 (dd, J¼12.2,
3.2 Hz, 1H), 3.83 (dd, J¼12.1, 2.7 Hz, 1H), 3.76 (dd, J¼9.4, 3.2 Hz, 1H),
0.91 (s, 9H), 0.11 (s, 6H). 13C NMR (125 MHz, CDCl3):
d 100.56, 80.10,
79.52, 75.10, 70.82, 69.41, 68.21, 65.00, 57.85, 55.05, 26.02, 18.40,
ꢁ5.33, ꢁ5.34. HRMS m/z calcd for C16H30O6Si [MþNa]þ: 369.1704.
Found 369.1711.
3.58 (dt, J¼9.9, 2.9 Hz, 1H), 3.37 (s, 3H), 2.52 (t, J¼2.4 Hz, 1H).13
C
NMR (125 MHz, CDCl3):
d 100.90, 79.93, 79.69, 75.31, 72.17, 68.19,
65.41, 61.60, 57.54, 55.15. HRMS m/z calcd for C10H16O6 [MþNa]þ:
255.0839. Found 255.0844.
4.10. Methyl-6-(tert-butyldimethylsilyloxy)-3-O-allyl-a-D-gal-
actopyranoside (7a)
4.5. 3-O-Allyl-D-galactal (4a)
Colorless oil, yield: 87%, Rf¼0.54 (ethyl acetate/petroleum
Colorless oil; yield: 86%, Rf¼0.27 (ethyl acetate/petroleum
ether¼1:1). 1H NMR (500 MHz, CDCl3):
d 6.00e5.93 (m, 1H), 5.32
ether¼1:1). 1H NMR (500 MHz, CDCl3):
d
6.45 (dd, J¼6.3,1.7 Hz,1H),
(dq, J¼17.2, 1.6 Hz, 1H), 5.22 (dt, J¼10.3, 1.4 Hz, 1H), 4.82 (d,
J¼3.9 Hz, 1H), 4.25e4.15 (m, 2H), 4.12e4.09 (m, 1H), 3.96 (ddd,
J¼9.7, 7.5, 3.9 Hz, 1H), 3.89 (dd, J¼10.4, 6.0 Hz, 1H), 3.82 (dd, J¼10.4,
5.6 Hz, 1H), 3.73 (t, J¼5.8 Hz, 1H), 3.43 (s, 3H), 2.64 (s, 1H), 2.16 (dd,
J¼8.2, 2.6 Hz, 1H), 0.91 (s, 9H), 0.09 (s, 6H). 13C NMR (125 MHz,
5.98e5.90 (m 1H), 5.32 (dq, J¼17.4, 1.8 Hz, 1H), 5.23 (dd, J¼10.4,
1.5 Hz, 1H), 4.70 (dt, J¼6.3, 2.0 Hz, 1H), 4.18 (dt, J¼4.1, 1.9 Hz, 1H),
4.11 (ddq, J¼5.7, 4.4, 1.5 Hz, 3H), 4.03 (dd, J¼11.4, 6.1 Hz, 1H),
3.95e3.91 (m, 1H), 3.88 (dd, J¼11.3, 4.5 Hz, 1H), 2.68 (s, 1H), 2.47 (s,
1H). 13C NMR (125 MHz, CDCl3): 145.22, 134.24,117.94, 99.49, 76.25,
70.62, 69.69, 63.85, 62.98. HRMS m/z calcd for C9H14O4 [MþNa]þ:
209.0784. Found 209.0787.
CDCl3):
d 134.80, 117.84, 99.67, 78.38, 71.01, 70.26, 68.68, 67.00,
62.88, 55.37, 26.00, 18.43, ꢁ5.25. HRMS m/z calcd for C16H32O6Si
[MþNa]þ: 371.1860. Found 371.1865.
4.6. 3-O-Propargyl-
D-galactal (4b)
4.11. Methyl-6-(tert-butyldimethylsilyloxy)-3-O-propargyl-
-galactopyranoside (7b)
a-
D
Colorless oil, yield: 88%, Rf¼0.25 (ethyl acetate/petroleum
ether¼1:1), 1H NMR (500 MHz, CDCl3):
d
6.47 (dd, J¼6.3, 1.8 Hz, 1H),
Colorless oil, yield: 89%, Rf¼0.51 (ethyl acetate/petroleum
4.71 (dt, J¼6.3, 2.0 Hz,1H), 4.39 (dtd, J¼3.8, 2.0, 0.8 Hz, 1H), 4.31 (dd,
J¼16.1, 2.4 Hz, 1H), 4.27 (dd, J¼16.0, 2.4 Hz, 1H), 4.18 (ddt, J¼4.7, 3.3,
1.7 Hz, 1H), 4.02 (ddd, J¼10.9, 6.0, 2.4 Hz, 1H), 3.98e3.94 (m, 1H),
3.89 (ddd, J¼11.6, 7.6, 4.2 Hz, 1H), 2.61 (d, J¼3.6 Hz, 1H), 2.50 (t,
J¼2.4 Hz,1H), 2.41 (dd, J¼8.4, 3.7 Hz,1H).13C NMR (125 MHz, CDCl3):
ether¼1:1). 1H NMR (500 MHz, CDCl3):
d
4.83 (d, J¼4.0 Hz, 1H),
4.46e4.36 (m, 2H), 4.23 (dt, J¼2.9, 1.4 Hz, 1H), 3.99 (ddd, J¼9.7, 8.0,
4.0 Hz,1H), 3.91 (dd, J¼10.3, 5.9 Hz, 1H), 3.83 (dd, J¼10.3, 5.4 Hz, 1H),
3.79e3.75 (m, 1H), 3.73 (dd, J¼9.7, 3.2 Hz, 1H), 3.44 (s, 3H), 2.68 (t,
J¼1.4 Hz,1H), 2.48 (t, J¼2.4 Hz,1H), 2.15 (d, J¼8.3 Hz,1H), 0.91 (s, 9H),
d
145.45, 99.12, 79.36, 76.33, 75.38, 70.80, 63.88, 62.93, 56.08. HRMS
0.10 (s, 6H). 13C NMR (125 MHz, CDCl3):
d 99.71, 80.08, 78.64, 75.12,
m/z calcd for C9H12O4 [MþNa]þ: 207.0628. Found 207.0630.
70.12, 68.71, 67.40, 62.91, 57.67, 55.45, 26.01, 18.44, ꢁ5.24, ꢁ5.30.
HRMS m/z calcd for C16H30O6Si [MþNa]þ: 369.1704. Found 369.1711.
4.7. Methyl-3-O-propargyl-4,6-benzylidene-a-D-mannopyr-
anoside (5b)
4.12. Methyl-6-(tert-butyldimethylsilyloxy)-3-O-allyl-b-D-gal-
actopyranoside (8a)
Colorless oil, yield: 95%, Rf¼0.39 (ethyl acetate/petroleum
ether¼1:2). 1H NMR (500 MHz, CDCl3):
d
7.51e7.47 (m, 2H),
Colorless oil, yield: 85%, Rf¼0.46 (ethyl acetate/petroleum
7.40e7.33 (m, 3H), 5.59 (s, 1H), 4.78 (d, J¼1.5 Hz, 1H), 4.49 (dd,
ether¼1:1). 1H NMR (500 MHz, CDCl3):
d 6.01e5.93 (m, 1H), 5.33

H. Xu et al. / Tetrahedron 72 (2016) 3490e3499
3495
(dq, J¼17.2, 1.6 Hz, 1H), 5.22 (dq, J¼10.4, 1.3 Hz, 1H), 4.23 (ddt,
J¼12.8, 5.8, 1.4 Hz, 1H), 4.20e4.16 (m, 2H), 4.06 (dd, J¼3.3, 1.1 Hz,
1H), 3.93 (dd, J¼10.3, 6.4 Hz, 1H), 3.85 (dd, J¼10.3, 5.5 Hz, 1H), 3.74
(dd, J¼9.5, 7.7 Hz, 1H), 3.54 (s, 3H), 3.45 (ddd, J¼6.5, 5.5, 1.2 Hz, 1H),
3.36 (dd, J¼9.4, 3.3 Hz, 1H), 0.90 (s, 9H), 0.09 (s, 6H). 13C NMR
2.4 Hz, 1H), 3.97 (dd, J¼5.3, 3.0 Hz, 1H), 3.58 (dd, J¼11.2, 3.0 Hz, 1H),
3.55e3.50 (m, 2H), 3.49e3.44 (m, 1H), 3.41 (t, J¼2.4 Hz, 1H), 3.25 (s,
3H), 1.82 (s, 3H). 13C NMR (126 MHz, DMSO-d6)
d 169.26, 98.38,
80.78, 76.92, 74.69, 71.11, 64.44, 60.50, 55.61, 54.37, 48.01, 22.68.
HRMS m/z calcd for C12H19NO6 [MþH]þ: 274.1285. Found 274.1284.
(125 MHz, CDCl3):
d 134.62, 118.01, 117.99, 104.09, 80.64, 74.85,
71.00, 66.05, 62.36, 56.94, 25.97, 18.42, ꢁ5.25, ꢁ5.29. HRMS m/z
4.18. 3-O-Allyl-b-D-lactopyranosyl azide (12a)
calcd for C16H32O6Si [MþNa]þ: 371.1860. Found 371.1864.
Colorless oil, yield: 70%, Rf¼0.58 (dichloromethane/meth-
4.13. Methyl-6-(tert-butyldimethylsilyloxy)-3-O-propargyl-
-galactopyranoside (8b)
b-
anol¼4:1). 1H NMR (500 MHz, DMSO-d6)
d 5.95e5.87 (m, 1H), 5.64
D
(d, J¼5.6 Hz, 1H), 5.31 (dq, J¼17.3, 1.8 Hz, 1H), 5.21 (d, J¼5.2 Hz, 1H),
5.12 (dq, J¼10.5, 1.6 Hz, 1H), 4.73 (d, J¼1.6 Hz, 1H), 4.69e4.67 (m,
1H), 4.67e4.64 (m, 1H), 4.57 (d, J¼3.7 Hz, 1H), 4.56 (s, 1H), 4.23 (d,
J¼7.8 Hz, 1H), 4.13 (ddt, J¼13.3, 5.3, 1.6 Hz, 1H), 4.05e4.00 (m, 1H),
3.83 (dd, J¼5.6, 3.3 Hz, 1H), 3.76 (ddd, J¼12.0, 5.6, 2.3 Hz, 1H), 3.62
(ddd, J¼11.7, 6.3, 4.8 Hz, 1H), 3.57e3.48 (m, 2H), 3.43 (ddt, J¼13.0,
8.7, 4.0 Hz, 3H), 3.39e3.34 (m, 2H), 3.20e3.15 (m, 1H), 3.05 (td,
Colorless oil, yield: 89%, Rf¼0.44 (ethyl acetate/petroleum
ether¼1:1). 1H NMR (500 MHz, CDCl3):
d
4.41 (ddd, J¼4.2, 2.4,
0.8 Hz, 2H), 4.20 (dd, J¼7.8, 1.0 Hz, 1H), 4.18 (d, J¼3.0 Hz, 1H), 3.94
(ddd, J¼10.3, 6.4, 1.3 Hz, 1H), 3.85 (ddd, J¼10.4, 5.3, 1.2 Hz, 1H), 3.77
(ddd, J¼9.1, 7.7, 1.1 Hz, 1H), 3.57e3.53 (m, 4H), 3.51e3.47 (m, 1H),
2.49 (t, J¼2.4 Hz, 1H), 0.90 (s, 9H), 0.09 (s, 6H). 13C NMR (125 MHz,
J¼8.5, 5.6 Hz, 1H). 13C NMR (125 MHz, DMSO-d6):
d 135.84, 116.19,
CDCl3):
d
104.09, 80.65, 79.85, 75.23, 74.67, 71.00, 66.39, 62.36,
103.64, 89.70, 80.79, 79.77, 76.96, 75.41, 74.77, 73.12, 69.55, 69.42,
64.66, 60.31, 60.04. HRMS m/z calcd for C15H25N3O10 [MþNa]þ:
430.1432. Found 430.1435.
57.57, 57.01, 25.97, 18.41, ꢁ5.27, ꢁ5.30. HRMS m/z calcd for
C
16H30O6Si [MþNa]þ: 369.1704. Found 369.1708.
4.14. 3-O-Allyl-
b
-D-galactopyranosyl azide (10a)
4.19. 3-O-Propargyl-b-D-Lactopyranosyl azide (12b)
Colorless oil, yield: 81%, Rf¼0.13 (ethyl acetate/petroleum
Colorless oil, yield: 65%, Rf¼0.49 (dichloromethane/meth-
ether¼1:1). 1H NMR (500 MHz, CDCl3):
d
5.99e5.92 (m, 1H), 5.34
anol¼4:1). 1H NMR (500 MHz, DMSO-d6)
d
5.67 (d, J¼5.6 Hz, 1H),
(dq, J¼17.3, 1.6 Hz, 1H), 5.27 (dq, J¼10.3, 1.3 Hz, 1H), 4.55 (d,
J¼8.6 Hz, 1H), 4.24 (ddt, J¼12.6, 5.8, 1.4 Hz, 1H), 4.18 (ddt, J¼12.6,
5.9, 1.4 Hz, 1H), 4.10 (dd, J¼3.4, 1.2 Hz, 1H), 4.01 (ddd, J¼11.9, 6.2,
0.9 Hz, 1H), 3.88 (dd, J¼11.9, 4.6 Hz, 1H), 3.73 (t, J¼9.0 Hz, 1H), 3.63
(ddd, J¼6.1, 4.6, 1.2 Hz, 1H), 3.39 (dd, J¼9.3, 3.3 Hz, 1H). 13C NMR
5.30 (d, J¼5.2 Hz, 1H), 4.71 (d, J¼5.9 Hz, 2H), 4.68 (d, J¼5.9 Hz, 2H),
4.57 (d, J¼8.7 Hz,1H), 4.30 (dd, J¼15.9, 2.4 Hz,1H), 4.25 (d, J¼6.0 Hz,
1H), 4.23 (d, J¼16.2 Hz, 1H), 3.84 (dd, J¼6.0, 3.2 Hz, 1H), 3.75 (ddd,
J¼12.0, 5.5, 2.3 Hz, 1H), 3.61 (ddd, J¼11.6, 6.3, 4.8 Hz, 1H), 3.53 (q,
J¼5.3 Hz, 1H), 3.48 (td, J¼6.7, 3.3 Hz, 1H), 3.44 (qd, J¼6.5, 6.1, 2.8 Hz,
3H), 3.39 (t, J¼2.4 Hz,1H), 3.35 (dd, J¼7.4, 3.9 Hz, 2H), 3.34e3.31 (m,
1H), 3.04 (td, J¼8.7, 5.4 Hz, 1H). 13C NMR (125 MHz, DMSO-d6)
(125 MHz, CDCl3): d 134.13, 118.56, 90.63, 80.44, 76.48, 71.24, 70.26,
66.89, 62.60. HRMS m/z calcd for C9H15N3O5 [MþNa]þ: 268.0904.
Found 268.0911.
d 103.56, 89.73, 80.78, 80.01, 79.70, 77.04, 77.00, 75.40, 74.78, 73.17,
69.46, 64.55, 60.23, 60.01, 56.08. HRMS m/z calcd for C15H23N3O10
4.15. 3-O-Propargyl-b-D-galactopyranosyl azide (10b)
[MþNa]þ: 428.1276. Found 428.1277.
Colorless oil, yield: 85%, Rf¼0.11 (ethyl acetate/petroleum
4.20. Methyl-3-O-allyl-a-L-rhamnopyranoside (13a)
ether¼1:1). 1H NMR (500 MHz, CDCl3):
4.59 (d, J¼8.6 Hz, 1H), 4.41
d
(d, J¼2.4 Hz, 2H), 4.21 (dd, J¼3.3,1.2 Hz,1H), 4.02 (dd, J¼11.9, 6.1 Hz,
1H), 3.90 (dd, J¼11.9, 4.6 Hz, 1H), 3.75 (dd, J¼9.3, 8.5 Hz, 1H), 3.67
(ddd, J¼6.0, 4.6, 1.3 Hz, 1H), 3.59 (dd, J¼9.3, 3.3 Hz, 1H), 2.53 (t,
Colorless oil, yield: 89%, Rf¼0.17 (ethyl acetate/petroleum
ether¼1:1). 1H NMR (500 MHz, CDCl3):
d 5.99e5.91 (m, 1H), 5.33
(dq, J¼17.2, 1.6 Hz, 1H), 5.24 (dq, J¼10.4, 1.4 Hz, 1H), 4.72 (d,
J¼1.6 Hz,1H), 4.19 (ddt, J¼12.6, 5.7,1.4 Hz,1H), 4.07 (ddt, J¼12.6, 5.9,
1.4 Hz, 1H), 4.01 (d, J¼2.0 Hz, 1H), 3.70e3.62 (m, 1H), 3.57e3.50 (m,
2H), 3.37 (s, 3H), 2.41 (d, J¼6.0 Hz, 1H), 2.34 (d, J¼8.2 Hz, 1H), 1.33
J¼2.4 Hz, 1H). 13C NMR (125 MHz, CDCl3):
d 90.66, 80.47, 79.44,
76.40, 75.77, 70.30, 67.29, 62.74, 57.85. HRMS m/z calcd for
C9H13N3O5 [MþH]þ: 244.0928. Found 244.0931.
(d, J¼6.2 Hz, 3H). 13C NMR (125 MHz, CDCl3):
d 134.39, 118.16,
4.16. Methyl 3-O-allyl-2-N-acetyl-
a
-D
-galactosamine (11a)
100.56, 79.59, 71.72, 70.58, 67.89, 67.68, 55.01, 17.80. HRMS m/z
calcd for C10H18O5 [MþNa]þ: 241.1046. Found 241.1049.
White solid, yield: 89%, Rf¼0.16 (dichloromethane/meth-
anol¼20:1). 1H NMR (500 MHz, DMSO-d6)
d
7.72 (d, J¼9.0 Hz, 1H),
4.21. Methyl-3-O-propargyl-a-L-rhamnopyranoside (13b)
5.89 (dd, J¼17.3, 10.6, 5.4 Hz, 1H), 5.23 (dq, J¼17.2, 1.9 Hz, 1H), 5.10
(dq, J¼10.3, 1.5 Hz, 1H), 4.62 (t, J¼5.5 Hz, 1H), 4.58 (d, J¼4.8 Hz, 1H),
4.51 (d, J¼3.7 Hz, 1H), 4.20 (ddd, J¼11.0, 9.0, 3.7 Hz, 1H), 4.09 (dd,
J¼13.0, 5.3, 1.6 Hz, 1H), 3.93 (dd, J¼7.0, 3.2, 1.6 Hz, 2H), 3.56e3.45
Colorless oil, yield: 90%, Rf¼0.17 (ethyl acetate/petroleum
ether¼1:1). 1H NMR (500 MHz, CDCl3):
4.72 (d, J¼1.6 Hz, 1H), 4.31
d
(dd, J¼2.3, 0.9 Hz, 2H), 4.09 (p, J¼1.8 Hz, 1H), 3.71e3.64 (m, 2H),
3.55 (td, J¼9.3, 1.9 Hz, 1H), 3.38 (s, 3H), 2.53 (t, J¼2.4 Hz, 1H), 2.39
(dd, J¼6.3, 2.7 Hz, 2H), 1.34 (d, J¼6.2 Hz, 3H). 13C NMR (125 MHz,
(m, 3H), 3.42 (dd, J¼11.1, 2.9 Hz, 1H), 3.24 (s, 3H), 1.81 (s, 3H). 13
C
NMR (126 MHz, DMSO-d6)
d 169.23, 135.93, 115.98, 98.39, 75.28,
71.09, 68.97, 64.44, 60.63, 54.31, 48.15, 22.65. HRMS m/z calcd for
CDCl3): d 100.56, 80.14, 79.90, 75.43, 71.56, 68.06, 67.78, 57.39,
C
12H21NO6 [MþH]þ: 276.1442. Found 276.1442.
55.02, 17.77. HRMS m/z calcd for C10H16O5 [MþNa]þ: 239.0890.
Found 239.0892.
4.17. Methyl 3-O-propargyl-2-N-acetyl-a-D-galactosamine
(11b)
4.22. 1-Propargyl-2-hexanol (15b)
White solid, yield: 90%, Rf¼0.19 (dichloromethane/meth-
Colorless oil, yield: 84%, Rf¼0.44 (ethyl acetate/petroleum
anol¼20:1). 1H NMR (500 MHz, DMSO-d6)
d
7.71 (d, J¼9.0 Hz, 1H),
ether¼1:4). 1H NMR (500 MHz, CDCl3):
d 4.26e4.13 (m, 2H), 3.80
4.69 (d, J¼5.1 Hz, 1H), 4.63 (t, J¼5.4 Hz, 1H), 4.50 (d, J¼3.6 Hz, 1H),
4.25 (dd, J¼15.9, 2.4 Hz, 1H), 4.23e4.18 (m, 1H), 4.16 (dd, J¼15.9,
(dp, J¼10.3, 4.5, 3.4 Hz, 1H), 3.58 (dd, J¼9.4, 2.9 Hz, 1H), 3.37 (dd,
J¼9.4, 7.8 Hz, 1H), 2.45 (t, J¼2.4 Hz, 1H), 2.30 (d, J¼3.2 Hz, 1H),

3496
H. Xu et al. / Tetrahedron 72 (2016) 3490e3499
1.51e1.28 (m, 6H), 0.91 (t, J¼7.1 Hz, 3H). 13C NMR (125 MHz, CDCl3):
4.28. Methyl-3,6-di-O-allyl-a-D-galactopyranoside (22)
d
79.52, 74.69, 74.45, 70.33, 58.50, 32.81, 27.66, 22.72, 13.99. HRMS
m/z calcd for C9H16O2 [MþH]þ: 157.1223. Found 157.1230.
Colorless oil, yield: 74%, Rf¼0.32 (ethyl acetate/petroleum
ether¼1:1). 1H NMR (500 MHz, CDCl3):
d 5.98e5.87 (m, 2H), 5.30
(ddq, J¼17.4,12.7, 1.6 Hz, 2H), 5.20 (ddq, J¼10.8, 9.6,1.4 Hz, 2H), 4.83
(d, J¼3.9 Hz, 1H), 4.18 (qdt, J¼12.7, 5.9, 1.4 Hz, 2H), 4.08 (d, J¼3.1 Hz,
1H), 4.05 (ddt, J¼5.5, 3.9, 1.4 Hz, 2H), 3.95 (ddd, J¼9.7, 7.5, 3.9 Hz,
1H), 3.88 (t, J¼5.8 Hz, 1H), 3.73 (dd, J¼10.0, 5.4 Hz, 1H), 3.66 (dd,
J¼10.0, 6.1 Hz, 1H), 3.55 (dd, J¼9.7, 3.2 Hz, 1H), 3.43 (s, 3H), 2.64 (t,
J¼1.4 Hz, 1H), 2.24 (d, J¼7.7 Hz, 1H). 13C NMR (125 MHz, CDCl3):
4.23. Methyl-3-O-butyl-b-D-galactopyranoside (16)
Colorless oil, yield: 68%, Rf¼0.34 (ethyl acetate). 1H NMR
(500 MHz, CDCl3):
d
4.19 (d, J¼7.7 Hz, 1H), 4.06 (d, J¼3.3 Hz, 1H),
3.96 (dd, J¼11.7, 6.4 Hz, 1H), 3.85 (d, J¼11.0 Hz, 1H), 3.71e3.64 (m,
2H), 3.59e3.54 (m, 1H), 3.56 (s, 3H), 3.51 (t, J¼5.8 Hz, 1H), 3.28 (dd,
J¼9.5, 3.4 Hz, 1H), 2.74 (m, 3H), 1.65e1.56 (m, 2H), 1.38 (ddt, J¼11.0,
7.4, 3.3 Hz, 2H), 0.92 (t, J¼7.4 Hz, 3H). 13C NMR (125 MHz, CDCl3):
d
134.60, 134.48, 117.96, 117.44, 99.64, 78.04, 72.65, 70.93, 69.64,
68.80, 68.41, 67.28, 55.49. HRMS m/z calcd for C13H22O6 [MþNa]þ:
297.1308. Found 297.1313.
d
104.15, 81.21, 74.45, 70.65, 70.05, 66.57, 62.37, 57.16, 32.01, 19.32,
13.94. HRMS m/z calcd for C11H22O6 [MþNa]þ: 273.1308. Found
4.29. Methyl-3,6-di-O-propargyl-a-D-galactopyranoside (23)
273.1313.
Colorless oil, yield: 70%, Rf¼0.20 (ethyl acetate/petroleum
4.24. Methyl-3-O-(1-bromo-butyl)-b-D-galactopyranoside (17)
ether¼1:1). 1H NMR (500 MHz, CDCl3):
d
4.83 (d, J¼3.9 Hz, 1H),
4.45e4.34 (m, 2H), 4.27e4.18 (m, 2H), 4.16 (dd, J¼3.4, 1.4 Hz, 1H),
3.99e3.91 (m, 2H), 3.81 (dd, J¼10.0, 5.2 Hz, 1H), 3.78e3.71 (m, 2H),
3.44 (s, 3H), 2.55 (s, 1H), 2.49 (t, J¼2.4 Hz, 1H), 2.46 (t, J¼2.4 Hz, 1H),
Colorless oil, yield: 65%, Rf¼0.36 (ethyl acetate). 1H NMR
(500 MHz, CDCl3)
d
4.19 (d, J¼7.8 Hz,1H), 4.07 (d, J¼3.4 Hz,1H), 3.96
(dd, J¼11.7, 6.2 Hz, 1H), 3.86 (dd, J¼11.7, 4.9 Hz, 1H), 3.77e3.59 (m,
3H), 3.57 (s, 3H), 3.52 (t, J¼5.8 Hz, 1H), 3.46 (t, J¼6.5 Hz, 2H), 3.29
(dd, J¼9.5, 3.3 Hz, 1H), 1.97 (ddd, J¼11.0, 8.3, 5.4 Hz, 2H), 1.79 (dt,
2.25 (d, J¼8.0 Hz, 1H). 13C NMR (125 MHz, CDCl3):
d 99.65, 79.84,
79.47, 78.14, 75.27, 74.98, 69.37, 68.75, 68.47, 67.54, 58.88, 57.66,
55.59. HRMS m/z calcd for C13H18O6 [MþH]þ: 271.1176. Found
271.1177.
J¼7.8, 6.4 Hz, 2H). 13C NMR (125 MHz, CDCl3)
d 104.24, 81.22, 74.40,
70.80, 69.34, 66.86, 62.41, 57.28, 33.72, 29.50, 28.57. HRMS m/z
calcd for C11H21O6Br [MþNa]þ: 351.0414. Found 351.0410.
4.30. Methyl-3,6-di-O-hexyl-a-D-galactopyranoside (24)
4.25. Methyl-3-O-hexyl-a-D-galactopyranoside (18)
Colorless oil, yield: 55%, Rf¼0.24 (ethyl acetate/petroleum
ether¼1:2). 1H NMR (500 MHz, CDCl3)
4.85 (d, J¼3.9 Hz, 1H), 4.11
d
Colorless oil, yield: 68%, Rf¼0.44 (ethyl acetate). 1H NMR
(d, J¼3.3 Hz,1H), 3.95 (ddd, J¼10.3, 6.7, 3.9 Hz,1H), 3.86 (t, J¼5.6 Hz,
1H), 3.74 (dd, J¼10.1, 5.4 Hz, 1H), 3.70e3.63 (m, 2H), 3.58e3.54 (m,
1H), 3.53e3.47 (m, 3H), 3.44 (s, 3H), 2.65 (s, 1H), 2.13 (d, J¼7.0 Hz,
(500 MHz, CDCl3):
d
4.86 (d, J¼3.9 Hz, 1H), 4.12 (d, J¼3.3 Hz, 1H),
3.99e3.88 (m, 2H), 3.86e3.81 (m, 1H), 3.81e3.76 (m, 1H), 3.65 (dt,
J¼9.3, 6.8 Hz, 1H), 3.58 (dt, J¼9.3, 6.6 Hz,1H), 3.50 (dd, J¼9.7, 3.4 Hz,
1H), 3.44 (s, 3H), 2.68 (d, J¼1.4 Hz, 1H), 2.51 (dd, J¼8.5, 3.7 Hz, 1H),
2.22 (d, J¼7.4 Hz, 1H), 1.66e1.57 (m, 2H), 1.39e1.22 (m, 6H), 0.88 (t,
1H), 1.68e1.51 (m, 4H), 1.39e1.22 (m, 12H), 0.90e0.87 (m, 6H). 13
C
NMR (126 MHz, CDCl3)
d 99.63, 78.78, 72.18, 70.44, 70.12, 68.79,
68.42, 67.18, 55.51, 31.80, 31.78, 30.06, 29.73, 25.89, 22.74, 22.72,
14.16. HRMS m/z calcd for C19H38O6 [MþNa]þ: 385.2561. Found
385.2565.
J¼6.8 Hz, 3H). 13C NMR (125 MHz, CDCl3):
d 99.71, 78.55, 70.38,
69.59, 68.41, 67.96, 63.16, 55.57, 31.74, 30.06, 25.86, 22.70, 14.13.
HRMS m/z calcd for C13H26O6 [MþH]þ: 279.1802. Found 279.1805.
4.31. Methyl-3-O-benzyl-6-O-(4-methoxybenzyl)-a-D-gal-
actopyranoside (25)
4.26. Methyl-3-O-(1-bromo-hexyl)-a-D-galactopyranoside
(19)
Colorless oil, yield: 74%, Rf¼0.17 (ethyl acetate/petroleum
Colorless oil, yield: 60%, Rf¼0.56 (ethyl acetate). 1H NMR
ether¼1:1). 1H NMR (500 MHz, CDCl3)
d 7.42e7.24 (m, 7H), 6.89 (d,
(500 MHz, CDCl3):
d
4.85 (d, J¼3.9 Hz, 1H), 4.12 (dd, J¼3.4, 1.4 Hz,
J¼8.6 Hz, 2H), 4.85 (d, J¼3.9 Hz, 1H), 4.74 (d, J¼11.7 Hz, 1H), 4.71 (d,
J¼11.8 Hz, 1H), 4.55 (d, J¼11.5 Hz, 1H), 4.51 (d, J¼11.6 Hz, 1H), 4.09
(d, J¼3.1 Hz, 1H), 4.02 (ddd, J¼9.7, 7.3, 3.9 Hz, 1H), 3.87 (t, J¼5.9 Hz,
1H), 3.81 (s, 3H), 3.74 (dd, J¼10.0, 5.5 Hz, 1H), 3.68 (dd, J¼10.0,
6.0 Hz,1H), 3.62 (dd, J¼9.7, 3.2 Hz,1H), 3.43 (s, 3H), 2.60 (s, 1H), 2.15
1H), 3.95 (dd, J¼11.6, 5.9 Hz, 1H), 3.93e3.89 (m, 1H), 3.83 (dd,
J¼11.5, 4.6 Hz, 1H), 3.80e3.77 (m, 1H), 3.66 (dt, J¼9.3, 6.7 Hz, 1H),
3.59 (dt, J¼9.3, 6.5 Hz, 1H), 3.50 (dd, J¼9.7, 3.3 Hz, 1H), 3.44 (s, 3H),
3.41 (t, J¼6.7 Hz, 2H), 1.86 (p, J¼6.9 Hz, 2H), 1.68e1.60 (m, 2H), 1.46
(qd, J¼7.3, 1.5 Hz, 2H), 1.40 (ddd, J¼10.9, 8.4, 5.4 Hz, 2H). 13C NMR
(d, J¼7.7 Hz, 1H). 13C NMR (125 MHz, CDCl3):
d 159.44, 138.02,
130.19, 129.50, 128.72, 128.13, 127.99, 113.97, 99.69, 78.50, 73.49,
(125 MHz, CDCl3):
d 99.72, 78.65, 70.11, 69.58, 68.46, 68.03, 63.18,
55.58, 33.91, 32.73, 29.90, 28.01, 25.38. HRMS m/z calcd for
72.08, 69.42, 68.89, 68.70, 67.40, 55.54, 55.42. HRMS m/z calcd for
22H28O7 [MþNa]þ: 427.1727. Found 427.1733.
C
13H25O6Br [MþH]þ: 357.0908. Found 357.0908.
C
4.27. Methyl-3-O-dodecyl-
a
-D-galactopyranoside (20)
4.32. Methyl-3,6-di-O-propargyl-b-D-galactopyranoside (28)
Colorless oil, yield: 63%, Rf¼0.1 (ethyl acetate/petroleum
Colorless oil, yield: 78%, Rf¼0.20 (ethyl acetate/petroleum
ether¼1:1). 1H NMR (500 MHz, CDCl3):
d
4.87 (d, J¼3.9 Hz, 1H), 4.12
ether¼1:1). 1H NMR (500 MHz, CDCl3):
4.40 (d, J¼2.4 Hz, 2H), 4.23
d
(d, J¼3.3 Hz,1H), 4.00e3.88 (m, 2H), 3.84 (dq, J¼6.9, 3.8, 3.1 Hz,1H),
3.82e3.78 (m, 1H), 3.65 (dt, J¼9.3, 6.8 Hz, 1H), 3.58 (dt, J¼9.3,
6.6 Hz,1H), 3.51 (dd, J¼9.7, 3.4 Hz,1H), 3.45 (s, 3H), 2.65 (s,1H), 2.45
(dd, J¼8.5, 3.6 Hz, 1H), 2.18 (d, J¼7.5 Hz, 1H), 1.62 (p, J¼6.9 Hz, 2H),
1.38e1.20 (m, 18H), 0.88 (t, J¼6.9 Hz, 3H). 13C NMR (125 MHz,
(dd, J¼2.4, 0.7 Hz, 2H), 4.21 (d, J¼7.8 Hz, 1H), 4.12 (dt, J¼3.1, 1.4 Hz,
1H), 3.85 (dd, J¼10.0, 5.8 Hz, 1H), 3.80 (dd, J¼10.0, 6.0 Hz, 1H), 3.75
(dd, J¼9.5, 7.7 Hz,1H), 3.66 (td, J¼5.9,1.1 Hz,1H), 3.59e3.55 (m, 1H),
3.56 (s, 3H), 2.59 (s, 1H), 2.50 (t, J¼2.4 Hz, 1H), 2.47 (t, J¼2.4 Hz, 1H).
2.49 (d, J¼3.0 Hz, 1H). 13C NMR (125 MHz, CDCl3):
d 104.02, 80.13,
CDCl3):
d
99.69, 78.54, 70.38, 69.58, 68.40, 67.95, 63.18, 55.57, 32.04,
79.64, 79.53, 75.43, 74.94, 73.42, 70.89, 68.97, 66.64, 58.94, 57.58,
57.21. HRMS m/z calcd for C13H18O6 [MþNa]þ: 293.0995. Found
293.0998.
30.10, 29.78, 29.75, 29.73, 29.70, 29.57, 29.47, 26.21, 22.81, 14.24.
HRMS m/z calcd for C19H38O6 [MþH]þ: 363.2741. Found 363.2746.

H. Xu et al. / Tetrahedron 72 (2016) 3490e3499
3497
4.33. Methyl-3,6-di-O-hexyl-
b-D
-galactopyranoside (29)
4.38. Phenyl-3,6-di-O-allyl-1-S-b-D-galactopyranoside (36)
Colorless oil, yield: 60%, Rf¼0.21 (ethyl acetate/petroleum
Colorless oil, yield: 71%, Rf¼0.33 (ethyl acetate/petroleum
ether¼1:2). 1H NMR (500 MHz, CDCl3)
d
4.85 (d, J¼3.9 Hz, 1H), 4.11
ether¼1:2). 1H NMR (500 MHz, CDCl3):
d 7.61e7.53 (m, 2H),
(d, J¼3.3 Hz,1H), 3.95 (ddd, J¼10.3, 6.7, 3.9 Hz,1H), 3.86 (t, J¼5.6 Hz,
1H), 3.74 (dd, J¼10.1, 5.4 Hz, 1H), 3.70e3.63 (m, 2H), 3.58e3.54 (m,
1H), 3.53e3.47 (m, 3H), 3.44 (s, 3H), 2.65 (s, 1H), 2.13 (d, J¼7.0 Hz,
1H), 1.68e1.51 (m, 4H), 1.39e1.22 (m, 12H), 0.89 (td, J¼7.1, 1.3 Hz,
7.34e7.28 (m, 3H), 5.99e5.87 (m, 2H), 5.31 (ddq, J¼17.0, 11.9, 1.6 Hz,
2H), 5.22 (tq, J¼10.5, 1.4 Hz, 2H), 4.54 (d, J¼9.8 Hz, 1H), 4.24 (ddt,
J¼12.6, 5.8, 1.4 Hz, 1H), 4.19 (ddt, J¼12.7, 5.9, 1.4 Hz, 1H), 4.12e4.08
(m, 1H), 4.06 (dt, J¼5.6, 1.5 Hz, 2H), 3.80e3.75 (m, 2H), 3.73 (dd,
J¼10.0, 5.7 Hz, 1H), 3.65 (t, J¼5.8 Hz, 1H), 3.40 (dd, J¼9.0, 3.3 Hz,
1H), 2.48 (d, J¼2.1 Hz, 1H), 2.47e2.44 (d, J¼2.0 Hz, 1H). 13C NMR
6H). 13C NMR (126 MHz, CDCl3)
d 103.98, 81.36, 73.62, 72.12, 70.79,
70.23, 69.72, 66.14, 57.00, 31.77, 31.75, 29.97, 29.69, 25.85, 25.83,
22.73, 22.69, 14.14. HRMS m/z calcd for C19H38O6 [MþNa]þ:
385.2561. Found 385.2566.
(125 MHz, CDCl3):
d 134.54, 134.43, 132.67, 132.45, 129.09, 128.05,
118.17, 117.46, 88.73, 81.49, 77.57, 72.73, 71.09, 69.34, 68.86, 66.78.
HRMS m/z calcd for C18H24O5S [MþH]þ: 353.1417. Found 353.1419.
4.34. Methyl-3-O-benzyl-6-O-(4-methoxybenzyl)-b-D-gal-
actopyranoside (30)
4.39. Phenyl-3,6-di-O-propargyl-1-S-b-D-galactopyranoside
(37)
Colorless oil, yield: 75%, Rf¼0.16 (ethyl acetate/petroleum
Colorless oil, yield: 68%, Rf¼0.21 (ethyl acetate/petroleum
ether¼1:1). 1H NMR (500 MHz, CDCl3):
d 7.42e7.24 (m, 7H),
ether¼1:2). 1H NMR (500 MHz, CDCl3):
d 7.59e7.52 (m, 2H),
6.92e6.86 (m, 2H), 4.77 (d, J¼11.8 Hz, 1H), 4.71 (d, J¼11.8 Hz, 1H),
4.53 (s, 2H), 4.18 (d, J¼7.8 Hz, 1H), 4.07e4.02 (m, 1H), 3.81 (s, 3H),
3.81e3.76 (m, 2H), 3.72 (dd, J¼9.9, 5.8 Hz, 1H), 3.61e3.57 (m, 1H),
3.56 (s, 3H), 3.43 (dd, J¼9.5, 3.3 Hz, 1H), 2.47 (dd, J¼2.5, 1.1 Hz, 1H),
7.34e7.28 (m, 3H), 4.55 (d, J¼9.7 Hz, 1H), 4.43e4.38 (m, 2H), 4.22
(dd, J¼2.5, 1.4 Hz, 2H), 4.16 (td, J¼3.1, 1.1 Hz, 1H), 3.87e3.81 (m, 2H),
3.77 (dd, J¼9.5, 2.1 Hz, 1H), 3.72e3.68 (m, 1H), 3.60 (dd, J¼9.0,
3.2 Hz, 1H), 2.59e2.55 (m, 1H), 2.49 (t, J¼2.4 Hz, 1H), 2.46 (t,
J¼2.4 Hz, 1H), 2.39 (dt, J¼4.3, 2.6 Hz, 1H). 13C NMR (125 MHz,
2.41 (d, J¼2.2 Hz, 1H). 13C NMR (125 MHz, CDCl3):
d 159.43, 137.76,
130.11, 129.60, 128.74, 128.21, 128.05, 113.97, 103.97, 80.53, 73.60,
CDCl3):
d 132.77, 132.27, 129.10, 128.13, 88.76, 81.22, 79.65, 79.56,
73.51, 72.04, 71.10, 68.92, 66.51, 57.12, 55.42. HRMS m/z calcd for
75.39, 74.91, 69.03, 68.88, 67.00, 58.97, 57.71. HRMS m/z calcd for
C
22H28O7 [MþNa]þ: 427.1727. Found 427.1730.
C
18H20O5S [MþH]þ: 349.1104. Found 349.1112.
4.35. 3,6-Di-O-allyl-
D-galactal (32)
4.40. Phenyl-3-O-benzyl-6-O-(4-methoxybenzyl)-1-S-b-D-gal-
actopyranoside (38)
White solid, yield: 88%, Rf¼0.44 (ethyl acetate/petroleum
ether¼1:2). 1H NMR (500 MHz, CDCl3):
d
6.42 (dd, J¼6.3,1.8 Hz,1H),
Colorless oil, yield: 73%, Rf¼0.31 (ethyl acetate/petroleum
5.98e5.89 (m, 2H), 5.32 (dq, J¼6.3, 1.6 Hz, 1H), 5.29 (dq, J¼6.3,
1.6 Hz, 1H), 5.23 (dt, J¼3.6, 1.4 Hz, 1H), 5.20 (dq, J¼2.9, 1.3 Hz, 1H),
4.68 (dt, J¼6.3, 2.0 Hz,1H), 4.17 (dtd, J¼3.7,1.9, 0.7 Hz,1H), 4.13 (ddt,
J¼12.6, 5.7, 1.4 Hz, 1H), 4.08 (dddt, J¼7.2, 4.5, 3.0, 1.4 Hz, 4H), 4.01 (t,
J¼6.2 Hz, 1H), 3.76 (d, J¼6.3 Hz, 2H), 2.54 (d, 1H). 13C NMR
ether¼1:2). 1H NMR (500 MHz, CDCl3):
d 7.60e7.55 (m, 2H),
7.39e7.22 (m, 10H), 6.92e6.85 (m, 2H), 4.76 (d, J¼11.8 Hz, 1H), 4.71
(d, J¼11.7 Hz, 1H), 4.54e4.50 (m, 3H), 4.09 (d, J¼2.9 Hz, 1H),
3.82e3.80 (m, 1H), 3.81 (s, 3H), 3.79e3.73 (m, 2H), 3.63 (t, J¼5.8 Hz,
1H), 3.45 (dd, J¼8.9, 3.3 Hz, 1H), 2.51e2.47 (m, 2H). 13C NMR
(125 MHz, CDCl3):
d
145.15, 134.49, 134.42, 117.69, 99.68, 75.47,
(125 MHz, CDCl3): d 159.46, 137.78, 132.62, 132.48, 130.19, 129.58,
72.71, 70.84, 69.61, 69.37, 63.13. HRMS m/z calcd for C12H18O4
129.07, 128.75, 128.23, 128.08, 128.00, 113.99, 88.69, 81.67, 77.63,
[MþNa]þ: 249.1097. Found 249.1103.
73.53, 72.17, 69.21, 69.00, 66.95, 55.44. HRMS m/z calcd for
C
27H30O6S [MþH]þ: 483.1836. Found 483.1838.
4.36. 3,6-Di-O-propargyl-D-galactal (33)
4.41. Methyl-3,6-di-O-allyl-a-D-mannopyranoside (40a)
Colorless oil, yield: 81%, Rf¼0.32 (ethyl acetate/petroleum
Colorless oil, yield: 20%, Rf¼0.31 (ethyl acetate/petroleum
ether¼1:2). 1H NMR (500 MHz, CDCl3):
6.44 (dd, J¼6.3,1.8 Hz,1H),
d
ether¼1:1). 1H NMR (500 MHz, CDCl3):
d 5.98e5.88 (m, 2H),
4.70 (dt, J¼6.3, 2.0 Hz,1H), 4.40e4.37 (m,1H), 4.29 (q, J¼2.7 Hz, 2H),
4.24 (dd, J¼4.7, 2.4 Hz, 2H), 4.13 (dt, J¼4.5, 1.6 Hz, 1H), 4.07 (t,
J¼6.2 Hz, 1H), 3.86 (d, J¼6.1 Hz, 2H), 2.49 (t, J¼2.4 Hz, 1H), 2.47 (t,
5.35e5.25 (m, 2H), 5.21 (ddt, J¼19.0, 10.4, 1.5 Hz, 2H), 4.77 (d,
J¼1.7 Hz, 1H), 4.20 (ddt, J¼12.6, 5.7, 1.4 Hz, 1H), 4.15e4.10 (m, 1H),
4.07 (dt, J¼5.7,1.6 Hz, 2H), 3.99 (dt, J¼3.5,1.9 Hz,1H), 3.86 (td, J¼9.2,
2.0 Hz, 1H), 3.75e3.70 (m, 3H), 3.59 (dd, J¼9.2, 3.3 Hz, 1H), 3.38 (s,
3H), 2.76 (d, J¼2.4 Hz, 1H), 2.51 (d, J¼2.9 Hz, 1H). 13C NMR
J¼2.4 Hz, 1H). 13C NMR (125 MHz, CDCl3):
d 145.35, 99.28, 79.42,
79.39, 75.37, 75.29, 75.05, 70.72, 69.16, 63.09, 58.90, 56.00. HRMS
m/z calcd for C12H14O4 [MþNa]þ: 245.0784. Found 245.0786.
(125 MHz, CDCl3):
d 134.58, 134.54, 117.93, 117.37, 100.64, 79.22,
72.72, 70.86, 70.49, 70.37, 68.01, 67.86, 55.11. HRMS m/z calcd for
4.37. O-Benzyl-6-O-(4-methoxybenzyl)-
b-D
-galactal (34)
C
13H22O6 [MþH]þ: 275.1489. Found 275.1495.
Colorless oil, yield: 79%, Rf¼0.42 (ethyl acetate/petroleum
4.42. Methyl-2,3-di-O-allyl-a-D-mannopyranoside (40b)
ether¼1:2). 1H NMR (500 MHz, CDCl3):
d 7.38e7.27 (m, 7H),
6.91e6.87 (m, 2H), 6.43 (dd, J¼6.3, 1.8 Hz, 1H), 4.71 (dt, J¼6.3,
2.0 Hz, 1H), 4.66 (d, J¼11.7 Hz, 1H), 4.60 (d, J¼11.7 Hz, 1H), 4.56 (d,
J¼11.5 Hz, 1H), 4.52 (d, J¼11.6 Hz, 1H), 4.21 (ddd, J¼4.1, 2.3, 1.5 Hz,
1H), 4.10 (ddt, J¼4.7, 3.1, 1.4 Hz, 1H), 4.01 (t, J¼6.2 Hz, 1H), 3.82 (s,
3H), 3.77 (dd, J¼6.2, 2.0 Hz, 2H), 2.57 (dd, J¼3.5, 0.9 Hz, 1H). 13C
Colorless oil, yield: 46%, Rf¼0.21 (ethyl acetate/petroleum
ether¼1:1). 1H NMR (500 MHz, CDCl3):
d 6.02e5.83 (m, 2H), 5.31
(ddt, J¼18.9, 17.5, 1.6 Hz, 2H), 5.21 (ddd, J¼10.3, 8.8, 1.5 Hz, 2H), 4.74
(d, J¼1.8 Hz, 1H), 4.21e4.11 (m, 3H), 4.08e4.02 (m, 1H), 3.97e3.87
(m, 2H), 3.82 (dd, J¼11.7, 5.2 Hz,1H), 3.74 (dd, J¼3.1, 1.8 Hz,1H), 3.61
(ddd, J¼9.5, 5.7, 3.5 Hz, 2H), 3.37 (s, 3H). 13C NMR (125 MHz, CDCl3):
NMR (125 MHz, CDCl3):
d 159.45, 145.20, 137.75, 130.01, 129.69,
128.79, 128.69, 128.11, 127.94, 113.98, 99.61, 75.49, 73.47, 70.83,
70.57, 69.10, 63.12, 55.43. HRMS m/z calcd for C21H24O5 [MþH]þ:
357.1697. Found 357.1700.
d 134.89, 134.57, 117.81, 117.68, 99.81, 79.38, 73.88, 72.45, 72.22,
70.74, 67.46, 63.12, 55.05. HRMS m/z calcd for C13H22O6 [MþH]þ:
275.1489. Found 275.1492.

3498
H. Xu et al. / Tetrahedron 72 (2016) 3490e3499
4.43. Methyl-3,6-di-O-propargyl-
a
-D-mannopyranoside (41a)
60.87, 57.27. HRMS m/z calcd for C25H40N6O16 [MþH]þ: 681.2574.
Found 681.2607.
Colorless oil, yield: 34%, Rf¼0.33 (ethyl acetate/petroleum
ether¼1:1). 1H NMR (500 MHz, CDCl3):
d
4.78 (d, J¼1.7 Hz, 1H),
Acknowledgements
4.35 (d, J¼2.4 Hz, 2H), 4.25 (d, J¼2.4 Hz, 2H), 4.09 (td, J¼3.2, 1.7 Hz,
1H), 3.89 (td, J¼9.5, 2.6 Hz, 1H), 3.84 (d, J¼1.3 Hz, 1H), 3.83 (d,
J¼2.0 Hz, 1H), 3.75 (ddd, J¼9.2, 5.5, 3.7 Hz, 2H), 3.40 (s, 3H), 2.60
(d, J¼2.8 Hz, 1H), 2.51 (t, J¼2.4 Hz, 1H), 2.45 (t, J¼2.4 Hz, 1H), 2.44
This study was supported by the National Natural Science
Foundation of China (Nos. 21272083).
(d, J¼3.0 Hz, 1H). 13C NMR (125 MHz, CDCl3):
d 100.71, 79.95,
79.74, 79.66, 75.30, 74.92, 70.75, 69.60, 68.06, 67.18, 58.96, 57.62,
55.19. HRMS m/z calcd for C13H18O6 [MþNa]þ: 293.0995. Found
293.1001.
Supplementary data
Supplementary data associated with this article can be found in
the online version, at http://dx.doi.org/10.1016/j.tet.2016.04.076.
4.44. Methyl-2,3-di-O-propargyl-a-D-mannopyranoside (41b)
References
Colorless oil, yield: 29%, Rf¼0.24 (ethyl acetate/petroleum
ether¼1:1). 1H NMR (500 MHz, CDCl3):
d
4.81 (d, J¼1.8 Hz, 1H),
1. Zhang, Q.; Rijssel, E. R. V.; Walvoort, M. T. C.; Overkleeft, H. S.; van der Marel, G.
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643e652.
4.43e4.27 (m, 4H), 4.06 (dd, J¼3.1, 1.8 Hz, 1H), 3.93e3.86 (m, 2H),
3.85e3.80 (m, 2H), 3.63 (ddd, J¼9.0, 5.0, 3.7 Hz, 1H), 3.40 (s, 3H),
2.51 (t, J¼2.4 Hz, 1H), 2.47 (t, J¼2.4 Hz, 1H). 13C NMR (125 MHz,
CDCl3): d 99.50, 79.89, 79.68, 79.34, 75.33, 75.16, 73.56, 72.19, 67.13,
62.85, 58.52, 57.60, 55.13. HRMS m/z calcd for C13H18O6 [MþNa]þ:
293.0995. Found 293.1002.
6. David, S.; Thieffry, A.; Forchioni, A. Tetrahedron Lett. 1981, 22, 2647e2650.
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4.45. Procedure for synthesis of Methyl-3-O-[10-(
b-D
-gal-
actopyranosyl)-[10,20,30]-triazol-40-yl]-methyl-
anoside (43)
b-D-galactopyr-
9. Demizu, Y.; Kubo, Y.; Miyoshi, H.; Maki, T.; Matsumura, Y.; Moriyama, N.;
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Copper sulfate pentahydrate (0.1 equiv) in H2O (2 mL) was
added in a mixture of -galactopyranosyl azide 10 (96 mg,
1.1 equiv) and Methyl-3-O-propargyl- -galactopyranoside 3b
b-D
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b-D
(100 mg, 0.25 mmol) in DCM (2 mL). Sodium ascorbate
(0.25 equiv) was then added and the mixture was stirred for 24 h
at room temperature. After the removal of the solvents, the
residue was purified by column chromatography (DCM/
MeOH¼2.5:1) to give 43 as colorless oil, yield: (153 mg, 81%),
Rf¼0.36 (DCM/MeOH¼2:1). 1H NMR (500 MHz, D2O):
d 8.32 (s,
1H), 5.71 (d, J¼9.2 Hz, 1H), 4.88 (d, J¼12.5 Hz, 1H), 4.77 (d,
J¼12.4 Hz, 1H), 4.32 (d, J¼7.1 Hz, 1H), 4.23 (t, J¼9.5 Hz, 1H),
4.18e4.15 (m, 1H), 4.09 (dd, J¼3.4, 0.9 Hz, 1H), 4.03e3.98 (m, 1H),
3.88 (dd, J¼9.8, 3.3 Hz, 1H), 3.82e3.73 (m, 4H), 3.68e3.65 (m,
1H), 3.59e3.53 (m, 2H), 3.55 (s, 3H). 13C NMR (125 MHz, D2O):
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d
124.97, 104.35, 88.71, 81.02, 79.02, 75.68, 73.61, 70.38, 69.23,
65.68, 62.14, 61.68, 61.51, 57.85. HRMS m/z calcd for C16H27N3O11
[MþNa]þ: 460.1538. Found 460.1536.
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b-D-
€
€
27. Dong, H.; Pei, Z. C.; Bystrom, S.; Ramstrom, O. J. Org. Chem. 2007, 72,
galactopyranosyl)-[10,20,30]-triazol-40-yl]-methyl-
actopyranoside (44)
b-D-gal-
1499e1502.
€
28. Dong, H.; Pei, Z. C.; Ramstrom, O. J. Org. Chem. 2006, 71, 3306e3309.
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Copper sulfate pentahydrate (0.2 equiv) in H2O (2 mL) was
added in a mixture of -galactopyranosyl azide 10 (164 mg,
2.2 equiv) and Methyl-3,6-di-O-propargyl- -galactopyranoside
b-D
b-D
28 (100 mg, 0.25 mmol) in DCM (2 mL). Sodium ascorbate
(0.5 equiv) was then added and the mixture was stirred for 24 h
at room temperature. After the removal of the solvents, the
residue was purified by column chromatography (DCM/
MeOH¼1.5:1) to give 44 as colorless oil; yield: (202 mg, 80%),
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d 8.36 (s,
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2H), 5.76 (d, J¼11.1 Hz, 2H), 4.93 (d, J¼12.5 Hz, 1H), 4.82 (d,
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4.20 (d, J¼2.3 Hz, 1H), 4.15 (d, J¼3.1 Hz, 2H), 4.06 (t, J¼6.0 Hz,
2H), 3.94 (dd, J¼9.7, 3.2 Hz, 2H), 3.88e3.81 (m, 7H), 3.61 (d,
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d 144.39,
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