4,6-Di-O-Benzylidenyl group-directed preparation of 2-deoxy-2-azido-α-D-galactopyranosides promoted by 3-O-TBDPS

Article abstract of DOI:10.1016/j.carres.2021.108237

In this study, we designed a method to prepare 2-deoxy-2-azido-α-D-galactopyranosidic bonds using 4,6-di-O-benzylidenyl-3-O-t-butyldiphenylsilyl protected 2-deoxy-2-azido-1-thio-D-galactopyranoside 5 as donors. The donor 5 gives a good to excellent α-sele

Full text of DOI:10.1016/j.carres.2021.108237

Carbohydrate Research 500 (2021) 108237
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4,6-Di-O-Benzylidenyl group-directed preparation of
2-deoxy-2-azido-
α
-D-galactopyranosides promoted by 3-O-TBDPS
,
*
,
,
Xing-Yong Lianga 1, Jing Yanga 1, Zhong-Hao Qiua, Lei Wanga, Todd L. Lowaryb,
Hua-Jun Shawn Fana
,
**
a School of Chemistry Engineering, Sichuan University of Science & Engineering, Zigong 643000, China
b Alberta Glycomics Centre and Department of Chemistry, University of Alberta, Edmonton, AB, T6G 2G2 Canada
A R T I C L E I N F O
A B S T R A C T
Keywords:
In this study, we designed a method to prepare 2-deoxy-2-azido-α-D-galactopyranosidic bonds using 4,6-di-O-
α
-Galactosamine
benzylidenyl-3-O-t-butyldiphenylsilyl protected 2-deoxy-2-azido-1-thio-D-galactopyranoside 5 as donors. The
Stereoselective glycosylations
Steric hindrance
donor 5 gives a good to excellent α-selectivity in the glycosylation with secondary alcohols, which was found to
be associated with the benzylidenyl on 4,6-di-O and TBDPS on 3-O of the donor 5. Compared with results of the
donor 6 and 7, the 3-O-TBDPS could increase the activity of the thioglycoside, and the lone pairs on 4,6-di-O-
benzylidenyl group enhanced the gg-cofnormation, which plays a role in improving the stereoselectivity.
Synthesis of a pentasaccharide
Finally, this method was demonstrated through the synthesis of a
α
-galactosamine -containing pentasaccharide
26.
1. Introduction
butyldiphenylsilyl protected 2-deoxy-1-thio-D-galactopyranoside as a
donor [7]. The approach gavean excellent α-selectivity inglycosylations,
Galactosamine is a key constituent in many important oligosaccha-
rides and glycoconjugates existing in biologically active natural prod-
ucts and clinical agents, including anthracyclines, angucyclines,
whichwasfoundtobeassociatedwiththeisopropylideneon3,4-di-Oand
TBDPSon6-Oofthedonor. Basedonthesefindings, wewillstudytherole
of other 2-deoxysugar counterparts in such reactions, particularly in the
aureolic acid antibiotics, etc. Galactosamine exists in either
form [1].
α
-or β-linked
preparation of 2-amino-2-deoxy-α-D-galactopyranosides.
The study demonstrated that the synthesis of β-form of galactos-
amine could be reliably achieved through the neighboring C-2-amide-
group or carbamate-based protecting group. For the stereoselective
2. Results and discussion
To avoid the participating functionalities on C-2, 2-deoxy-2-azido-1-
preparation of
α
-form of galactosamine, on the contrary, the glycosyl
thio-galactosides are employed for the introduction of α-galactosamines.
donors with non-neighboring functionality on C-2, Such as 2-azido, have
been extensively explored in order to maximize the anomeric effect,
often with the aid of solvent effect or some cyclic protecting groups [2].
Recently, several research groups have reported alternative approaches
to a galactosamine through these strategies. Among them, the corre-
sponding 2-azido [3], 2,3-trans-oxazolidinone [4], 4,6-O-benzylidenyl
[5], and 4,6-O-di-tert-butylsilylene [6] glycosamine derivatives are
frequently used as essential building blocks.
The azido moiety is a non-participating functionality and is stable under
a wide variety of reaction conditions, also can readily be reduced to an
amine with reagents such as phosphines and thiols, and by catalytic
hydrogenation.
Following the design, this study begins with the synthesis with the
preparation of the thioglycosides 3 and 5–7 as illustrated in Scheme 1.
All of the thioglycosides have a nonparticipating azido moiety at C-2 site
[8] and a cyclic prototective group at O-3,4 or O-4,6, respectively. The
synthesis of these thioglycosides starting from the known thioglycoside
1, which can be prepared from D-galactose following the Mong’s method
In our previous study, we reported the preparation of 2-deoxy-
α-D-
galactopyranosidic bonds using 3,4-di-O-isopropylidene-6-O-t-
* Corresponding author.
** Corresponding author.
E-mail addresses: levesonk@163.com (X.-Y. Liang), Fan27713@yahoo.com (H.-J. Shawn Fan).
1
These authors contributed equally.
https://doi.org/10.1016/j.carres.2021.108237
Received 9 October 2020; Received in revised form 15 January 2021; Accepted 15 January 2021
Available online 28 January 2021
0008-6215/© 2021 Elsevier Ltd. All rights reserved.

X.-Y. Liang et al.
Carbohydrate Research 500 (2021) 108237
reaction with benzoyl chloride in pyridine led to 7 in 95% yield (see
Scheme 2).
To investigate the
α and β stereoselectivity of glycosylation reaction,
we first applied thioglycoside 3 as the donor for synthesizing 2-amino-2-
deoxy-α-D-galactopyranosides. The glycosylation was performed using
the alcohol (8a-j, 1.0 equiv), thioglycoside 3 or 5 (1.2 equiv), NIS (1.5
equiv), and TfOH (0.1 equiv), at ꢀ 30 to 0 ◦C in CH2Cl2. The product of
the coupling between thioglycoside 3 and acceptor 8a [10] show a mild
α
-selectivity (α:β, 3:1, entry 1, Table 1). The product stereochemistry
was confirmed by 3JH-1,H-2 in 1H NMR in CDCl3. For
α
-anomers, 3JH-1,H-2
3
is 3–5 Hz, while for β-anomers JH-1,H-2 is 9–10 Hz [11]. Besides, the
chemical shift of the anomeric carbon in the α-anomer resonated at <
100 ppm. In comparison, the chemical shift of the anomeric carbon in
the β-anomer resonated at > 100 ppm. The selectivity of the glycosyl-
ation was not superior to existed methods. Next, we carried out the
glycosylation reaction of 3 with a more hindered secondary acceptor 8b.
Scheme 1. Preparation of Compound 3, 5, 6 and 7. Reagents and conditions:
(a) (CH3)2C(OMe)2, PPTs, acetone, r.t., 4 h, 71%; (b) TBDPS-Cl, Imidazole,
DMF, 25 ◦C, 4 h, 79%; (c) PhCH(OMe)2, PPTs, CH3CN, r.t., 4 h; (d) for 5:
TBDPS-Cl, Imidazole, DMF, 25 ◦C, 4 h, 81%; for 6: BzCl, Pyridine, 45 ◦C, 1 h,
95%; for 7: BnBr, NaH, DMF, 0–25 ◦C, 2 h, 92%.
The results are similar to the previous result (yield of 87%,
2, Table 1).
α:β, 5:1, entry
As a comparison, we set out to survey the glycosylation of another
thioglycoside 5 with the acceptors 8a and 8b. The results showed that
stereoselectivity of glycosylation reaction between the thioglycoside 5
with 8a is slightly improved over the selectivity of thioglycoside 3 with
[9]. Acetalization of thioglycoside 1 via 2,2-dimethoxy propane yield
71% of 2, following by the reaction with TBDPS-Cl to form O-6 silicon
ether 3 with a yield of 79%. On the other hand, acetalization of thio-
glycoside 1 via benzaldehyde dimethanol will result in 4 with a yield of
74%. Treatment with TBDPS-Cl, thioglycoside 4 can be converted into
its derivatives 5 in a yield of 81% Alkylation of thioglycoside 4 with
benzyl bromide and sodium hydride gave 6 in 92% yield; Finally,
6a (yield of 90%, α:β, 5:1, entry 3, Table 1). However, the α-selectivity
was significantly improved between the thioglycoside 5 and 8b [12]
(α:β, 10:1, entry 4, Table 1). To further investigate the steric hindrance
of the acceptor, we surveyed the glycosylation of 5 with a variety of
alcohols 8c-j [13]. All the glycosylations were run under NIS and TfOH
at ꢀ 30 ◦C and CH2Cl2 as the solvent. As summarized in Table 1, we can
Scheme 2. Synthesis of the pentasaccharide 26.
2

X.-Y. Liang et al.
Carbohydrate Research 500 (2021) 108237
Table 1
Glycosylations of donors 3 or 5 with alcohol 8a-j.
Entry
1
Donors
3
Accepors
Products
Yieldsb
(
α
/β)c
93% (3:1)
2
3
3
5
87% (5:1)
90% (5:1)
4
5
81% (10:1)
5
5
91% (2:1)
6
5
87% (5:4)
(continued on next page)
3

X.-Y. Liang et al.
Carbohydrate Research 500 (2021) 108237
Table 1 (continued)
Entry
Donors
Accepors
Products
Yieldsb
(
α
/β)c
7
8
5
5
87% (15:1)
85% (13:1)
9
5
71% (α-only)
10
11
5
5
80% (
α
-only)
-only)
74% (
α
12
5
86% (7:1)
aAll glycosylations were performed by employing the donor (1.2 equiv) and the acceptor (1.0 equiv) in the presence of NIS (1.5 equiv), catalytic TfOH (0.1 equiv), and
4 A molecular sieves (4A M.S.) in CH2Cl2, at ꢀ 30 to 0 ◦C.
b
The total yield of isomers.
c
Determined on the basis of the 1H NM.
4

X.-Y. Liang et al.
Carbohydrate Research 500 (2021) 108237
see that all acceptors surveyed demonstrated either mild α-selectivity
Table 2
Glycosylations of Donors 6 or 7 with Alcohol 8a, h-i.
(10c-d), highly
α-selectivity (10e-f, j), or
α-only (10g-i) glycoside
products with 71–91% yields with the
α-anomer as the dominant
product.
Analysis of experimental results in Table 1, reactions with the pri-
mary alcohols 8a and 8c-d provided much lower α-selectivities than
reactions with more hindered secondary alcohols 8b and 8e-j (entries 3,
5–6 vs entries 4, 7–12). Further illustrated that the steric hindrance from
various acceptors would further enhance the
α-selectivity behavior.
Based on these results, we hypothesized that that benzylidenyl on 4,6-di-
O and TBDPS on 3-O of the donor could control the nucleophile to attack
the a-face of the donor. The X-ray diffraction analysis of the donor 5
(Fig. 1) also show that the β-face of the anomeric carbon of 5 is indeed of
potential resistance.
En.
1a
donor
acceptor
product
6
8c
The effect of 4,6-di-O-benzylidenyl group on the stereoselectivity of
the glycosylation has been reported in literature [5]. To better under-
stand the behavior of 3-O-TBDPS during the glycosylation reaction, the
glycosylation of 3-O-Bz (6) or 3-O-Bn thioglycosides (7) (Table 2) were
investigated.
2a
7
8c
Neither 6 nor 7 showed α-selectivity in the glycosylation with pri-
mary alcohol 8c. In particular, there are more β-product than α-product
in the reaction of compound 7. Thioglycoside 6 could not react with the
secondary hydroxyl 8h. The reaction with 8i could only be carried out at
room temperature in a low yield and a mild α-selectivity (yield of 18%,
α
-only). The glycosylation between 7 and 8h could not work at low
temperature, but could be carried out at room temperature providing a
complex product 13 in a yield of 76%. It was difficult to identify the ratio
of isomers 13 due to some impurities which could not be separated. The
3a
4a
6
7
8h
8h
No Reaction
α
-selectivity of the reaction between 7 and 8i was excellent at both low
temperature and room temperature. With the increase of temperature,
the yield of the reaction slightly increased, but the by-products increased
at the same time.
Comparing the results of glycosylations of thioglycoside 5 in Table 1
with the results of glycosylations of thioglycosides 6–7 in Table 2, It
displayed that 3-O-TBDPS could significantly improve the activity of the
donor. This enabled thioglycoside 5 to react with various alcohols at a
lower temperature, and the yield was significantly better than that of 6
or 7. However, we also see that 3-O-TBDPS has a little effect on the
stereoselectivity of the reaction. 3-O-TBDPS did not significantly affect
the steric hindrance of the β-face of the anomeric carbon. The key to the
stereoselectivity was 4,6-di-O-benzylidenyl group.
5a
6b
6
6
8i
8i
No Reaction
Finally, we targeted the preparation of a pentaccharide 26 [14],
7a
7
7
8i
8i
8b
a
All glycosylations were performed at ꢀ 30 to 0 ◦C.
All glycosylations were performed at 0–25 ◦C.
b
Fig. 1. X-ray of the donor 5.
5

X.-Y. Liang et al.
Carbohydrate Research 500 (2021) 108237
which contained 2-amino-2-deoxy-
α
-D-galactopyranosidic bonds by
4.07 (dd, J = 7.5, 5.0 Hz, 1H), 3.97–3.91 (m, 2H)), 3.85 (td, J = 6.5, 2.5
Hz, 1H), 3.38 (dd, J = 10.5, 7.5 Hz, 1H), 2.31 (s, 3H), 1.40 (s, 3H), 1.34
(s, 3H), 1.05 (s, 9H); 13C NMR (125 MHz, CDCl3): δ 138.3, 135.6, 135.6,
133.4, 133.3, 129.8, 129.7, 128.0, 127.7, 127.7, 110.4, 86.1, 78.4, 77.2,
76.9, 72.5, 63.9, 62.8, 28.2, 26.8, 26.3, 21.2, 19.2; HRMS–ESI–TOF
calcd for [M+Na]+ C32H39N3NaO4SSi: 612.2323. Found: 612.2324.
utilizing the developed approach. Treatment of 16 [13] and 17 [15]
with NIS/TfOH yielded disaccharide 18 in 91% yield. Subsequent
desilylation via TBAF in THF liberated the 3,5-OH of disaccharide 18,
thus affording 19 in 86% yield. Then, the coupling between 19 and
thioglycoside 20 [16] at ꢀ 30 ◦C for 1 h produced the tetrasaccharide 21
in 71% yield. Subsequent deacylation of levulinoyl protecting group via
Hydrazine acetate liberated the 2-OH of the middle arabino-moiety of
the tetrasaccharide 22. Alcohol 22 underwent a facile NIS/TfOH pro-
moted glycosylation with the thioglycoside 5, to afford exclusively
4.2. Toluene 4,6-di-O-benzylidenyl-3-O-tert-butyldiphenylsilyl-1-thio-2-
azido-2-deoxy-β-D-galactopyranoside (5)
α
-linked product 23(H-1: δ 5.17, J1,2 = 3.6 Hz; C-1: δ 99.0, JH1-C1 [17] =
To a solution of 1 (627 mg, 2.00 mmol) in dry CH3CN (10 mL) was
added Benzaldehyde dimethyl acetal (0.44 mL, 2.90 mmol) and PTSA
(31.3 mg, 0.164 mmol). The reaction mixture was stirred at rt for 4 h.
The resulting mixture was added H2O and extracted with CH2Cl2. The
organic layer was washed with saturated aq NaHCO3 and brine, dried
over Na2SO4, filtered and concentrated. The organic layer was washed
with saturated aqueous NaHCO3 and brine, dried over Na2SO4, filtered
and concentrated. The residue 4, imidazole (0.47 g, 6.9 mmol) and tert-
Butyldiphenylchlorosilane (0.72 mL, 2.8 mmol) were dissolved in dry
CH2Cl2 (7.2 mL). The reaction stirred under N2 for 2 h, then quenched
with MeOH. The resulting mixture was added H2O and CH2Cl2. The
organic layer was washed with saturated aqueous NaHCO3 and brine,
dried over Na2SO4, filtered and concentrated in vacuo. The residue was
purified by column chromatography (15:1, Petroleum ether–EtOAc) to
afford compound 5 as a white semisolid (771 mg, 65%). Rf 0.3 (10:1,
172.5 > 165.0), in 81% yield (Scheme2). Deprotection of 23 involving
desilylation via Pyridine hydrofluoride in pyridine generated the cor-
responding alcohol 24 in 83% yield. Then de-O-acetylation of Benzoyl
ester and Troc afforded the polyol 25 in 89% yield. Finally, the reduction
of azide and simultaneous hydrolysis of benzylidenyl group generated
the target pentasaccharide 26 in 73% yield.
3. Conclusion
In summary, we reported a methodology for the synthesis of 2-azido-
2-deoxy-α-galactopyranosides by using 4,6-di-O-benzylidenyl-3-O-t-
butyldiphenylsilyl protected 2-deoxy-2-azido-1-thio-D-galactopyrano-
side 5 as donor. Although the method only showed excellent stereo-
selectivity in the glycosylation with secondary alcohols, not so good
with primary alcohols. Finally, the approach was successfully applied to
the synthesis of a protected pentasaccharide derivative 26. The exact
mechanism is advancing by means of computational chemistry.
petroleum ether–EtOAc); [
α]
D 40.4 (c 0.6, CHCl3); 1H NMR (500 MHz,
CDCl3): δ 7.75–7.70 (m, 4H), 7.60 (d, J = 8.0 Hz, 2H), 7.47–7.38 (m,
9H), 7.27 (t, J = 8.0 Hz, 2H), 7.04 (d, J = 8.0 Hz, 2H), 5.11 (s, 1H), 4.30
(d, J = 9.5 Hz, 1H), 4.22 (dd, J = 7.5, 2.0 Hz, 1H), 3.79 (t, J = 9.5 Hz,
1H), 3.70 (dd, J = 12.0, 2.0 Hz, 1H), 3.64 (dd, J = 9.5, 3.0 Hz, 1H), 3.45
(d, J = 2.5 Hz, 1H), 3.10 (d, J = 1.0 Hz, 1H), 2.34 (s, 3H), 1.03 (s, 9H);
13C NMR (125 MHz, CDCl3): δ 138.3, 138.0, 135.9, 135.8, 134.3, 134.0,
132.4, 130.0, 129.8, 129.7, 129.0, 128.1, 127.9, 127.6, 126.8, 126.4,
100.6, 85.8, 77.2. 74.7, 74.5, 69.6, 69.2, 62.2, 26.7, 21.3, 19.3;
HRMS–ESI–TOF calcd for [M+Na]+ C36H39N3NaO4SSi: 660.2328.
Found: 660.2333.
4. Experiment procedures
Experimental Details. Dry CH2Cl2 was taken from a solvent puri-
fication system after successive passage through alumina columns. Dry
CH3OH was obtained via storage in a sealed bottle with activated 4 Å M
S. overnight at rt. Unless otherwise stated, all reactions were carried out
under an argon atmosphere and were monitored by TLC on silica gel 60
F254 (0.25 mm, Merck). Spots were visualized by UV light and/or by
charring with 10% H2SO4 in EtOH. Column chromatography was per-
4.3. Toluene 4,6-di-O-benzylidenyl-3-O-benzyl-1-thio-2-azido-2-deoxy-
1
formed on silica gel 60 (40–60
μ
m. H NMR spectra were recorded at
β-D-galactopyranoside (6)
500 and 600 MHz; and chemical shifts were referenced to CHCl3 (7.26
ppm, CDCl3). 13C NMR spectra were recorded at 125 or 150 MHz, and
chemical shifts were referenced to internal CDCl3 (77.06 ppm, CDCl3).
Optical rotations were measured on a PerkinElmer 241 polarimeter at
22 ± 2 ◦C in units of (degree⋅mL)/(dm⋅g). Electrospray ionization
spectra were recorded on an Aligent Technologies 6220 TOF spec-
trometer with samples dissolved in CH2Cl2, CH3OH, or H2O.
To a solution of 4 (438 mg, 1.10 mmol) in pyridine (5.5 mL) was
added benzoyl chloride (253 μL, 2.20 mmol). After being stirred for 1 h
at 50 ◦C, the reaction was quenched with methanol, diluted with CH2Cl2,
and then the mixture was washed with aq 1 N HCl, saturated aqueous
NaHCO3 and brine. The organic layer was separated and dried over
anhydrous Na2SO4, filtered, and concentrated. The residue was purified
by column chromatography (7:1, petroleum ether–EtOAc) to afford
compound 6 as a White solid (522 mg, 94.5%). Rf 0.35 (4:1, petroleum
ether–EtOAc). 1H NMR (600 MHz, CDCl3): δ 8.03 (dd, J = 8.4, 1.2 Hz,
2H), 7.66 (d, J = 7.8 Hz, 2H), 7.57 (t, J = 7.8 Hz, 1H), 7.43–7.34 (m,
7H), 7.08 (d, J = 8.4 Hz, 2H), 5.49 (s, 1H), 5.05 (dd, J = 10.8, 3.6 Hz,
1H), 4.55 (d, J = 9.6 Hz, 1H), 4.48 (d, J = 3.0 Hz, 1H) 4.42 (dd, J = 12.6,
1.2 Hz, 1H), 4.06 (dd, J = 12.6, 1.8 Hz, 1H), 4.00 (t, J = 10.2 Hz, 1H),
3.64 (d, J = 1.8 Hz, 1H), 2.36 (s, 3H); 13C NMR (150 MHz, CDCl3): δ
165.97, 138.7, 137.6, 134.65, 133.55, 129.99, 129.16, 129.11, 128.48,
128.09, 126.43, 126.22, 100.8, 85.5, 77.25, 77.04, 76.8, 74.7, 72.8,
69.69, 69.24, 58.7, 29.7, 21.3; HRMS–ESI–TOF calcd for [M+Na]+
C36H39N3NaO4SSi: 660.2328. Found: 660.2333.
4.1. Toluene 3,4-di-O-isopropylidene-6-O-tert-butyldiphenylsilyl-1-thio-
2-azido-2-deoxy-β-D-galactopyranoside (3)
To a solution of 1 (618 mg, 2.00 mmol) in dry acetone (20 mL) was
added 2,2-Dimethoxypropane (0.37 ml, 3.00 mmol) and PTSA (38.2 mg,
0.20 mmol). The reaction mixture was stirred at rt for 4 h. The resulting
mixture was added H2O and extracted with CH2Cl2. The organic layer
was washed with saturated aqueous NaHCO3 and brine, dried over
Na2SO4, filtered and concentrated. The residue 2, imidazole (0.47 g, 6.9
mmol) and tert-Butyldiphenylchlorosilane (0.72 mL, 2.8 mmol) were
dissolved in dry CH2Cl2 (7.2 mL). The reaction stirred under N2 for 2 h,
then quenched with MeOH. The resulting mixture was added H2O and
CH2Cl2. The organic layer was washed with saturated aqueous NaHCO3
and brine, dried over Na2SO4, filtered and concentrated in vacuo. The
residue was purified by column chromatography (10:1, Petroleum
ether–EtOAc) to afford compound 3 as a white semisolid (836 mg, 71%).
4.4. Toluene 4,6-di-O-benzylidenyl-3-O-benzyl-1-thio-2-azido-2-deoxy-
β-D-galactopyranoside (7)
To a solution of 4 (484 mg, 1.21 mmol) in dry DMF (6 mL) was added
Rf 0.5 (6:1, petroleum ether–EtOAc); [
α
]D 33.1 (c 0.9, CHCl3); 1H NMR
benzyl bromide (288 μ
L, 2.42 mmol). After being stirred for 0.5 h at 0 ◦C,
(500 MHz, CDCl3): δ 7.71–7.68 (m, 4H), 7.46–7.36 (m, 8H), 7.09 (d, J =
8.0 Hz, 2H), 4.33 (d, J = 10.5 Hz, 1H), 4.24 (dd, J = 5.0, 2.0 Hz, 1H),
then sodium hydridethe (116 mg, 4.84 mmoL) was added, the reation
mixture was gradually warmed to rt and was stirred for 1 h at the same
6

X.-Y. Liang et al.
Carbohydrate Research 500 (2021) 108237
temperature,The mixture was diluted with CH2Cl2, and then the mixture
was washed with aq 1 N HCl, saturated aqueous NaHCO3 and brine. The
organic layer was separated and dried over anhydrous Na2SO4, filtered,
and concentrated. The residue was purified by column chromatography
(7:1, petroleum ether–EtOAc) to afford compound 6 as a White solid
(543 mg, 91.6%). Rf 0.35 (4:1, petroleum ether–EtOAc). 1H NMR (600
MHz, CDCl3): δ 7.76 (dd, J = 8.0, 1.5 Hz, 2H), 7.73 (dd, J = 8.0, 1.5 Hz,
2H), 7.62 (d, J = 8.0 Hz, 2H), 7.48–7.39 (m, 9H), 7.29 (d, J = 15 Hz,
2H), 7.05 (d, J = 8.0 Hz, 2H), 5.12 (s, 1H), 4.31 (d, J = 9.5 Hz, 1H), 4.23
(dd, J = 12.5, 2.0 Hz, 1H), 3.80 (t, J = 10 Hz, 1H), 3.71 (dd, J = 12.5,
2.0 Hz, 1H), 3.65 (dd, J = 10, 3.5 Hz, 1H), 3.47 (dd, J = 3.5, 1.0 Hz, 1H),
3.12 (d, J = 1.0 Hz, 1H), 2.36 (s, 3H) 1.55 (s, 1H) 1.04 (s, 9H); 13C NMR
(150 MHz, CDCl3): δ 138.3, 138.0, 135.9, 135.8, 134.3, 134.0, 132.4,
130.0, 129.8, 129.7, 128.9, 128.1, 127.9, 127.6, 126.8, 126.4, 100.6,
85.75, 77.3, 77.0, 76.8, 74.65, 69.6, 69.2, 26.7, 21.3, 19.3;
HRMS–ESI–TOF calcd for [M+Na]+ C36H39N3NaO4SSi: 660.2328.
Found: 660.2333.
CDCl3): δ 7.72–7.66 (m, 4H), 7.42–7.19 (m, 36H), 5.18 (s, 1H), 5.11 (d,
J = 1.0 Hz, 1H), 4.98 (d, J = 1.0 Hz, 1 H), 4.79 (d, J = 3.5 Hz, 1H), 4.62
(d, J = 12.0 Hz, 1H), 4.55–4.43 (m, 10H), 4.41 (d, J = 12.0 Hz, 1H),
4.20–4.00 (m, 11H), 3.91–3.78 (m, 5H), 3.71–3.55 (m, 5H), 3.38–3.34
(m, 1H), 3.27 (dd, J = 8.5, 3.5 Hz, 1H), 3.25 (t, J = 7.0 Hz, 2H),
1.61–1.54 (m, 8H), 1.49 (s, 3H), 1.34 (s, 3H), 1.38–1.26 (m, 8H), 1.04 (s,
9H); 13C NMR (125 MHz, CDCl3): δ 138.2, 138.2, 138.1, 137.8, 137.7,
137.7, 135.7, 135.5, 133.3, 133.3, 129.7, 129.7, 128.4, 128.3, 127.9,
127.8, 127.8, 127.7, 127.6, 127.6, 127.5, 109.5, 106.4, 106.1, 105.8,
97.7, 88.7, 88.3, 87.3, 83.7, 83.2, 81.6, 80.2, 80.1, 77.2. 73.4, 73.2,
72.4, 72.3, 72.3, 72.0, 72.0, 71.8, 69.8, 68.6, 67.6, 65.9, 65.4, 62.4,
61.4, 51.5, 29.7, 29.5, 29.3, 29.1, 28.8, 28.4, 26.8, 26.7, 26.2, 26.1,
CHCl3); 1H NMR (500 MHz, CDCl3): δ 7.71–7.64 (m, 4H),D7.43–7.20 (m,
32H), 7.13 (s, 4H), 5.22 (s, 1H), 5.17 (d, J = 1.5 Hz, 1H), 5.01 (d, J = 1.5
Hz, 1 H), 4.58–4.44 (m, 10H), 4.42–4.38 (m, 2H), 4.29 (d, J = 9.0 Hz, 1
H), 4.20–4.02 (m, 9H), 3.94–3.68 (m, 10H), 3.59–3.53 (m, 2H),
3.40–3.37 (m, 1H), 3.32 (t, J = 8.5 Hz, 1H), 3.25 (t, J = 7.0 Hz, 2H),
1.61–1.54 (m, 8H), 1.54 (s, 3H), 1.33 (s, 3H), 1.38–1.26 (m, 8H), 1.04 (s,
9H); 13C NMR (125 MHz, CDCl3): δ 138.2, 138.0, 138.0, 137.9, 137.7,
137.7, 135.6, 135.5, 133.2, 133.1, 129.8, 129.7, 128.4, 128.3, 127.9,
127.8, 127.8, 127.7, 127.6, 127.6, 127.5, 127.5, 110.2, 106.8, 106.5,
106.1, 101.3, 88.7, 87.2, 83.8, 83.3, 83.0, 81.4, 80.2, 80.1, 77.2. 73.3,
73.1, 72.4, 72.3, 72.1, 72.0, 69.9, 67.6, 66.1, 65.4, 65.1, 62.1, 51.5,
29.5, 29.3, 29.1, 28.8, 28.4, 26.8, 26.8, 26.7, 26.2, 26.1, 19.2;
HRMS–ESI–TOF calcd for [M+Na]+ C90H108N6NaO17Si: 1595.7438.
Found: 1595.7443.
19.2; For β: Rf 0.18 (5:1, petroleum ether–EtOAc); [α] 80.0 (c 0.7,
4.5. General procedure for the glycosylation of 3 or 5
A mixture of donor 3 or 5 (1.2 equiv), acceptor (1.0 equiv), and
freshly activated 4 Å molecular sieves in dry CH2Cl2 (to a 0.1 N solvent)
was cooled to ꢀ 30 ◦C. The suspension was stirred for 15 min, then NIS
(1.5 equiv), TfOH (0.1 equiv) was added. The reaction mixture was
stirred for 1–2 h at the same temperature. The reaction mixture was
◦
gradually warmed to 0 C and quenched with Et3N. The mixture was
diluted with CH2Cl2 and added Na2S2O3, filtered through celite and
concentrated in vacuo. The crude material was quickly purified by col-
umn chromatography to give the product. The ratio of the isomers was
detected by NMR in all cases.
4.8. Methyl 4,6-di-O-benzylidenyl-3-O-tert-butyldiphenylsilyl-2-azido-2-
deoxy-α,β-D-galactopyranosyl-(1 → 6)-2,3,4-tri-O-benzoyl-α-D-
4.6. Methyl 3,4-di-O-isopropylidene-6-O-tert-butyldiphenylsilyl-2-azido-
mannopyranoside (10a)
2-deoxy-α,β-D-galactopyranosyl-(1 → 6)-2,3,4-tri-O-benzoyl-α-D-
mannopyranoside (9a)
Prepared from 5 (142 mg, 0.223 mmol) and 8a (94 mg, 0.186 mmol)
following the general Procedure. The residue was purified by column
chromatography (Petroleum ether–EtOAc, 4:1 to 6:1) to afford com-
Prepared from 3 (212 mg, 0.360 mmol) and 8a (152 mg, 0.300
mmol) following the general Procedure. The residue was purified by
column chromatography (Petroleum ether–EtOAc, 8:1) to afford com-
pound 10a as a light syrup (169 mg, yield of 89.5%,
α
:β = 3:1). For
α
: Rf
1
0.25 (3:1, petroleum ether–EtOAc); [
α]
28.7 (c 0.9, CHCl3); H NMR
(500 MHz, CDCl3): δ 8.11 (dd, J = 7.5, 1.D0 Hz, 2H), 7.91 (dd, J = 7.5, 1.0
Hz, 2H), 7.83 (dd, J = 7.5, 1.0 Hz, 2H), 7.78 (dd, J = 7.5, 1.0 Hz, 2H),
7.73 (dd, J = 7.5, 1.0 Hz, 2H), 7.60–7.34 (m, 17H), 7.28–7.23 (m, 3H),
5.85 (dd, J = 10.0, 3.5 Hz, 1H), 5.77 (t, J = 10.0 Hz, 1H), 5.64 (q, J =
1.5 Hz, 1H), 5.04 (d, J = 3.5 Hz, 1H), 5.01 (s, 1H), 4.87 (d, J = 1.5 Hz,
1H), 4.38 (dd, J = 10.0, 3.5 Hz, 1H), 4.28–4.23 (m, 1H), 3.98 (dd, J =
12.0, 1.5 Hz, 1H), 3.94 (dd, J = 10.5, 3.5 Hz, 1H), 3.88 (dd, J = 11.0, 7.0
Hz, 1H), 3.62 (dd, J = 11.0, 2.0 Hz, 1H), 3.56 (dd, J = 12.0, 1.5 Hz, 1H),
3.47 (d, J = 3.5 Hz, 1H), 3.36 (s, 1H), 3.32 (s, 3H), 1.09 (s, 9H); 13C NMR
(125 MHz, CDCl3): δ 165.6, 165.4, 165.4, 137.8, 135.9, 135.9, 134.4,
133.5, 133.5, 133.1, 133.0, 129.9, 129.9, 129.8, 129.7, 129.3, 129.2,
129.0, 128.8, 128.6, 128.5, 128.3, 128.1, 127.8, 127.5, 126.1, 100.4,
98.7, 98.4, 77.2. 75.3, 70.6, 70.0, 69.6, 69.4, 69.0, 67.2, 66.8, 62.8,
61.0, 55.2, 26.9, 26.3, 19.4; For β: Rf 0.25 (3:1, petroleum ether–EtOAc);
pound 9a as a light syrup (270 mg, yield of 92.7%, α:β = 3:1). Rf 0.3 (5:1,
petroleum ether–EtOAc); 1H NMR (500 MHz, CDCl3): δ 8.13 (d, J = 7.0
Hz, 2H), 8.10 (d, J = 7.0 Hz, 0.7H), 7.96 (d, J = 7.0 Hz, 2H), 7.92 (d, J =
7.5 Hz, 0.7H), 7.82 (d, J = 7.0 Hz, 2.7H), 7.67–7.23 (m, 25H), 5.97 (t, J
= 10.0 Hz, 1.4H), 5.88 (dd, J = 10.0, 3.0 Hz, 1.4H), 5.82 (t, J = 10.0 Hz,
0.7H), 5.68 (q, J = 1.5 Hz, 1H), 5.64 (q, J = 1.5 Hz, 0.4H), 4.99 (d, J =
1.5 Hz, 1.4H), 4.89 (d, J = 3.0 Hz, 1H), 4.47 (dd, J = 8.5, 5.0 Hz, 1H),
4.31–4.26 (m, 2.7H), 4.21 (dd, J = 5.0, 1.5 Hz, 0.4H), 4.16–3.74 (m,
7.4H), 3.67 (dd, J = 8.5, 3.5 Hz, 1H), 3.52 (s, 3H), 3.39 (dd, J = 8.5, 3.5
Hz, 1.4H), 1.50 (s, 1H), 1.50 (s, 2.5H), 1.36 (s, 2.5H), 1.50 (s, 1H), 1.01
(s, 3H), 0.98 (s, 7.5H); 13C NMR (125 MHz, CDCl3): δ 165.6, 165.5,
165.4, 135.6, 135.5, 135.5, 133.5, 133.4, 133.1, 130.0, 129.8, 129.7,
129.3, 129.1, 129.0, 110.3, 109.6, 102.1, 98.7, 98.5, 97.9, 77.2. 73.9,
73.4, 72.8, 72.3, 70.6, 70.5, 70.2, 70.0, 69.9, 69.6, 68.4, 67.4, 67.0,
66.8, 65.7, 62.7, 62.4, 61.7, 55.5, 55.4, 28.4, 28.3, 26.7, 26.3, 26.2,
19.1, 14.2; HRMS–ESI–TOF calcd for [M+Na]+ C55H57N3NaO13Si:
994.3558. Found: 994.3552.
[
α
]
ꢀ 83.1 (c 0.8, CHCl3); 1H NMR (500 MHz, CDCl3): δ 8.10 (dd, J =
7.5D, 1.0 Hz, 2H), 7.94 (dd, J = 7.5, 1.0 Hz, 2H), 7.81 (dd, J = 7.5, 1.0 Hz,
2H), 7.77 (dd, J = 7.5, 1.0 Hz, 2H), 7.75 (dd, J = 7.5, 1.0 Hz, 2H),
7.61–7.22 (m, 20H), 5.89 (dd, J = 10.0, 3.5 Hz, 1H), 5.72 (t, J = 10.5 Hz,
1H), 5.65 (q, J = 1.5 Hz, 1H), 5.14 (s, 1H), 4.98 (d, J = 1.5 Hz, 1H),
4.38–4.34 (m, 1H), 4.25 (d, J = 8.0 Hz, 1H), 4.11–4.08 (m, 2H),
3.83–3.76 (m, 2H), 3.72 (dd, J = 12.0, 1.5 Hz, 1H), 3.57 (dd, J = 10.0,
3.5 Hz, 1H), 3.55 (s, 3H), 3.43 (d, J = 3.5 Hz, 1H), 3.02 (s, 1H), 1.07 (s,
9H); 13C NMR (125 MHz, CDCl3): δ 165.9, 165.6, 165.4, 137.8, 136.0,
135.8, 134.1, 133.4, 133.1, 132.6, 133.0, 129.9, 129.8, 129.7, 129.4,
129.2, 129.0, 128.8, 128.5, 128.2, 128.1, 127.8, 127.6, 126.1, 102.6,
100.6, 98.3, 77.2. 74.6, 72.7, 70.7, 70.0, 69.9, 69.2, 68.9, 67.6, 62.3,
64.4, 55.5, 26.9, 26.8, 19.4; HRMS–ESI–TOF calcd for [M + NH4]+
C57H61N4O13Si: 1037.3999. Found: 1037.3988.
4.7. 8-Azidooctyl 3,4-di-O-isopropylidene-6-O-tert-butyldiphenylsilyl-2-
azido-2-deoxy-α,β-D-galactopyranosyl-(1 → 2)-3,5-di-O-benzyl-α-D-
arabinofuanosyl-(1 → 5)-2,3-di-O-benzyl-
α-D-arabinofuanosyl-(1 → 5)-
2,3-di-O-benzyl- -D-arabinofuanoside (9b)
α
Prepared from 3 (76 mg, 0.129 mmol) and 8b (120 mg, 0.108 mmol)
following the general Procedure. The residue was purified by column
chromatography (Petroleum ether–EtOAc, 5:1) to afford compound 9b
as a light syrup (148 mg, yield of 87.1%, α:β = 5:1). For α: Rf 0.2 (5:1,
petroleum ether–EtOAc); [
α]
D 78.0 (c 0.7, CHCl3); 1H NMR (500 MHz,
7

X.-Y. Liang et al.
Carbohydrate Research 500 (2021) 108237
4.9. 8-Azidooctyl 4,6-di-O-benzylidenyl-3-O-tert-butyldiphenylsilyl-2-
chromatography (Petroleum ether–EtOAc, 2:1) to afford compound 10d
azido-2-deoxy-
α
,β-D-galactopyranosyl-(1 → 2)-3,5-di-O-benzyl-
α
-D-
as a light syrup (75 mg, yield of 86.6%, α:β = 5:4. For α: Rf 0.25 (3:1,
arabinofuanosyl-(1 → 5)-2,3-di-O-benzyl-
α
-D-arabinofuanosyl-(1 → 5)-
petroleum ether–EtOAc); [
α
]D 157.3 (c 1.1, CHCl3); 1H NMR (600 MHz,
2,3-di-O-benzyl- -D-arabinofuanoside (10b)
α
CDCl3): δ 7.77 (t, J = 6.6 Hz, 4H), 7.51–7.36 (m, 9H), 7.29 (t, J = 7.8 Hz,
2H), 5.92–5.85 (m, 1H), 5.34 (t, J = 7.8 Hz, 1H), 5.22 (d, J = 10.2 Hz,
1H), 5.11 (s, 1H), 4.97 (d, J = 3.0 Hz, 1H), 4.65–4.58 (m, 2H), 4.41 (d, J
= 7.8 Hz, 1H), 4.13–4.09 (m, 2H), 4.06 (dd, J = 10.8, 3.0 Hz, 1H),
3.87–3.83 (m, 2H), 3.74 (dd, J = 12.6, 1.8 Hz, 1H), 3.54 (d, J = 3.0 Hz,
1H), 3.35 (s, 1H), 1.43 (s, 9H), 1.08 (s, 9H); 13C NMR (150 MHz, CDCl3):
δ 169.7, 155.3, 137.7, 135.95, 135.83, 134.1, 132.6, 131.5, 130.1,
129.9, 128.92, 128.18, 127.90, 127.56, 126.1, 118.8, 100.48, 100.22,
80.1, 77.24, 77.03, 76.8, 75.4, 69.71, 69.12, 69.05, 66.3, 63.3, 60.6,
54.2, 31.9, 29.72, 29.38, 26.8, 22.7, 19.3, 14.1. For β: Rf 0.15 (3:1,
Prepared from 5 (67 mg, 0.105 mmol) and 8b (97 mg, 0.088 mmol)
following the general Procedure. The residue was purified by column
chromatography (Petroleum ether–EtOAc, 7:2) to afford compound 10b
as a light syrup (114 mg, yield of 80.6%, α:β = 10:1). Rf 0.35 (2:1, pe-
troleum ether–EtOAc); [
α]
69.0 (c 2.0, CHCl3); 1H NMR (500 MHz,
D
CDCl3): δ 7.76–7.73 (m, 4H), 7.53–7.49 (m, 2H), 7.44–7.21 (m, 39H),
5.12 (s, 1H), 5.02 (s, 1H), 5.01 (s, 1H), 4.99 (s, 1H), 4.98 (d, J = 3.5 Hz,
1H), 4.65 (d, J = 12.0 Hz, 1H), 4.55–4.44 (m, 10H), 4.41 (d, J = 12.0 Hz,
1H), 4.17–4.01 (m, 11H), 3.87–3.80 (m, 4H), 3.72–3.66 (m, 2H),
3.59–3.53 (m, 3H), 3.50 (dd, J = 10.5, 5.5 Hz, 1H), 3.43 (d, J = 3.5 Hz,
1H), 3.38–3.33 (m, 1H), 3.32 (s, 1H), 3.25 (d, J = 7.0 Hz, 2H), 1.61–1.53
(m, 8H), 1.38–1.26 (m, 8H), 1.09 (s, 9H); 13C NMR (125 MHz, CDCl3): δ
138.1, 138.1, 137.8, 137.8, 137.7, 135.9, 135.8, 134.2, 132.8, 130.0,
129.9, 128.8, 128.4, 128.3, 128.2, 128.1, 127.9, 127.8, 127.8, 127.7,
127.6, 127.6, 127.5, 126.2, 126.1, 106.3, 106.1, 106.1, 100.3, 98.8,
88.7, 88.2, 87.2, 83.6, 83.3, 83.2, 81.0, 80.4, 80.1, 77.2. 75.2, 73.3,
72.3, 72.3, 72.1, 72.0, 71.9, 69.7, 69.5, 69.0, 67.6, 66.0, 65.8, 63.3,
61.0, 51.5, 29.5, 29.3, 29.1, 28.8, 26.8, 26.8, 26.7, 26.1, 19.3;
HRMS–ESI–TOF calcd for [M + NH4]+ C94H112N7O17Si: 1638.7884.
Found: 1638.7878.
petroleum ether–EtOAc); [
α]
D 80.1 (c 0.9, CHCl3); 1H NMR (600 MHz,
CDCl3): δ 7.77–7.74 (m, 5H), 7.54 (dd, J = 7.8, 1.8 Hz, 2H), 7.47–7.45
(m, 1H), 7.43–7.38 (m, 7H), 7.30 (t, J = 7.8 Hz, 2H), 5.92–5.86 (m, 1H),
5.33 (dd, J = 17.4, 1.8Hz, 1H), 5.19 (d, J = 10.2 Hz, 1H), 5.14 (s, 1H),
4.71 (dd, J = 13.8, 6.0 Hz, 1H), 4.64 (dd, J = 13.2, 6.0 Hz, 1H), 4.48 (d,
J = 8.4 Hz, 1H), 4.33 (dd, J = 10.2, 3.0 Hz, 1H), 4.17 (d, J = 8.4 Hz, 1H),
4.14 (dd, J = 12.0, 1.2 Hz, 1H), 3.85–3.81 (m, 2H), 3.74 (dd, J = 12.6,
1.8 Hz, 1H), 3.56 (dd, J = 10.2, 3.6 Hz, 1H), 3.43 (d, J = 3.0 Hz, 1H),
3.02 (d, J = 0.6 Hz, 1H), 1.45 (s, 9H), 1.06 (s, 9H); 13C NMR (150 MHz,
CDCl3): δ 169.8, 137.8, 135.98, 135.93, 135.87, 135.83, 134.0, 132.6,
131.6, 129.99,129.88, 128.91, 128.16, 127.82, 127.61, 126.2, 118.5,
102.3, 100.6, 79.9, 77.2, 77.0, 76.8, 74.5, 72.7, 69.5, 68.8, 66.32, 66.18,
64.0, 54.0, 28.3, 26.8, 19.4. HRMS–ESI–TOF calcd for [M+Na]+
C40H50N4NaO9Si: 781.3245. Found: 781.3231.
4.10. Methyl 4,6-di-O-benzylidenyl-3-O-tert-butyldiphenylsilyl-2-azido-
2-deoxy-α,β-D-galactopyranosyl-(1 → 5)-2,3-di-O-benzoyl-α-D-
arabinofuranoside (10c)
4.12. (1R,2S,5R)-2-isopropyl-5-methylcyclohexyl 4,6-di-O-benzylidenyl-
3-O-tert-butyldiphenylsilyl-2-azido-2-deoxy-α,β-D-galactopyranoside
Prepared from 5 (95 mg, 0.149 mmol) and 8c (46 mg, 0.124 mmol)
following the general Procedure. The residue was purified by column
chromatography (Petroleum ether–EtOAc, 8:1 to 4:1) to afford com-
(10e)
Prepared from 5 (105 mg, 0.165 mmol) and 8e (22 mg, 0.141 mmol)
following the general Procedure. The residue was purified by column
chromatography (Petroleum ether–EtOAc, 15:1) to afford compound
pound 10c as a light syrup (101 mg, yield of 91.0%, α:β = 2:1). For α: Rf
0.3 (5:1, petroleum ether–EtOAc); [
α
]
94.1 (c 1.1, CHCl3); 1H NMR
(600 MHz, CDCl3): δ 8.07 (d, J = 7.2 HDz, 2H), 8.04 (d, J = 7.8 Hz, 2H),
7.74 (t, J = 6.6 Hz, 4H), 7.61–7.55 (m, 4H), 7.50–7.31 (m, 16H), 7.24 (t,
J = 7.8 Hz, 2H), 5.48 (d, J = 1.8 Hz, 1H), 5.39 (dd, J = 6.0, 1.8 Hz, 1H),
5.15 (d, J = 3.0 Hz, 1H), 5.06 (s, 2H), 4.38–4.35 (m, 1H), 4.35 (dd, J =
10.8, 3.6 Hz, 1H), 4.07 (d, J = 12.6 Hz, 1H), 3.95 (dd, J = 10.8, 3.6 Hz,
1H), 3.92–3.87 (m, 2H), 3.71 (d, J = 12.0 Hz, 1H), 3.54 (d, J = 1.8 Hz,
2H), 3.41 (s, 3H), 1.06 (s, 9H); 13C NMR (150 MHz, CDCl3): δ 165.6,
137.8, 135.9, 135.9, 134.3, 133.5, 133.5, 132.9, 130.9, 129.9, 129.9,
129.7, 129.2, 129.2, 128.9, 128.5, 128.5, 128.1, 127.8, 127.5, 126.1,
106.7, 100.5, 99.1, 82.3, 80.6, 77.2, 77.0, 76.8, 75.5, 69.5, 69.2, 67.2,
10e as a light syrup (82 mg, yield of 86.9%,
α:β = 15:1). Rf 0.6 (5:1,
1
petroleum ether–EtOAc); H NMR (600 MHz, CDCl3): δ 7.77–7.74 (m,
4H), 7.55 (d, J = 6.6 Hz, 2H), 7.47–7.37 (m, 8H), 7.76 (t, J = 7.8 Hz,
2H), 5.13 (s, 1H), 4.27 (d, J = 8.4 Hz, 1H), 4.09 (d, J = 12.0 Hz, 1H),
3.82 (q, J = 10.2 Hz, 1H), 3.73 (dd, J = 12.0, 1.2 Hz, 1H), 3.55 (dd, J =
10.2, 3.6 Hz, 1H), 3.47–3.42 (m, 2H), 2.98 (s, 1H), 2.38–2.33 (m, 1H),
2.06 (d, J = 12.6 Hz, 1H), 1.64 (d, J = 10.8 Hz, 2H), 1.32–1.26 (m, 4H),
1.05 (s, 9H), 0.93 (d, J = 6.6 Hz, 3H), 0.90 (d, J = 6.6 Hz, 3H), 0.77 (d, J
= 7.2 Hz, 3H); 13C NMR (150 MHz, CDCl3): δ 138.2, 136.0, 135.9, 134.3,
132.9, 129.9, 129.7, 128.9, 128.2, 127.8, 127.5, 126.4, 100.8, 99.3,
77.9, 77.2, 77.0, 74.8, 73.0, 69.1, 65.9, 64.2, 47.9, 40.3, 34.4, 31.6,
29.7, 26.8, 25.3, 23.4, 22.3, 20.9, 19.4, 16.0; HRMS–ESI–TOF calcd for
[M+Na]+ C39H51N3NaO5Si: 692.3496. Found: 692.3488.
65.6, 63.0, 61.0, 54.9, 30.6, 29.7, 26.8, 19.4, 19.2, 13.7, 1.0; For β: Rf
1
0.25 (5:1, petroleum ether–EtOAc); [
α
]
14.3 (c 0.5, CHCl3); H NMR
(600 MHz, CDCl3): δ 8.07 (q, J = 7.8 HzD, 4H), 7.76 (d, J = 7.8 Hz, 4H),
7.59–7.53 (m, 4H), 7.46–7.36 (m, 12H), 7.30 (t, J = 7.8 Hz, 2H), 5.48 (d,
J = 1.8 Hz, 1H), 5.47 (d, J = 6.0 Hz, 1H), 5.15 (d, J = 10.8 Hz, 2H), 4.48
(td, J = 6.6, 3.0 Hz, 1H), 4.36–4.32 (m, 2H), 4.17 (d, J = 12.0 Hz, 1H),
3.90–3.86 (m, 2H), 3.75 (d, J = 12.0 Hz, 1H), 3.61 (dd, J = 10.2, 3.6 Hz,
4.13. Methyl 4,6-di-O-benzylidenyl-3-O-tert-butyldiphenylsilyl-2-azido-
2-deoxy-α,β-D-galactopyranosyl-(1 → 4)-2,3,6-tri-O-benzyl-α-D-
glucopyranoside (10f)
1H), 3.47 (s, 3H), 3.44 (d, J = 3.6 Hz, 1H), 3.07 (s, 1H), 1.05 (s, 9H); 13
C
NMR (150 MHz, CDCl3): δ 165.9, 165.5, 137.8, 136.0, 135.9, 134.1,
133.4, 133.4, 132.7, 130.0, 129.9, 129.9, 129.8, 129.3, 129.3, 128.9,
128.5, 128.4, 128.1, 127.8, 127.6, 126.2, 106.8, 102.5, 100.7, 82.2,
81.2, 77.6, 77.3, 77.0, 76.8, 74.7, 72.8, 69.3, 68.9, 66.4, 64.0, 54.9,
31.9, 29.7, 29.4, 26.8, 22.7, 19.4, 14.1, 1.0; HRMS–ESI–TOF calcd for
[M+Na]+ C49H51N3NaO11Si: 908.3191. Found: 908.3199.
Prepared from 5 (86 mg, 0.135 mmol) and 8f (52 mg, 0.112 mmol)
following the general Procedure. The residue was purified by column
chromatography (Petroleum ether–EtOAc, 15:1 to 12:1) to afford com-
pound 10f as a light syrup (93 mg, yield of 84.9%,
α
:β = 13:1). For
α
: Rf
1
0.35 (8:1, petroleum ether–EtOAc); [
α]
61.5 (c 1.1, CHCl3); H NMR
(600 MHz, CDCl3): δ 7.80–7.75 (m, 4H),D7.49–7.16 (m, 26H), 5.77 (d, J
= 4.0 Hz, 1H), 5.08 (d, J = 10.5 Hz, 1H), 4.97 (s, 1H), 4.89 (d, J = 11.0
Hz, 1H), 4.74 (d, J = 12.0 Hz, 1H), 4.60 (d, J = 12.0 Hz, 1H), 4.58 (d, J
= 4.0 Hz, 1H), 4.43 (d, J = 12.0 Hz, 1H), 4.27 (d, J = 12.0 Hz, 1H),
4.13–4.10 (m, 1H), 4.05 (t, J = 9.0 Hz, 1H), 3.83 (t, J = 10.0 Hz, 1H),
3.80 (dd, J = 11.0, 3.5 Hz, 1H), 3.71 (d, J = 12.5, 1.0 Hz, 1H), 3.65 (ddd,
J = 10.0, 4.0, 1.5 Hz, 1H), 3.55 (dd, J = 10.0, 4.0 Hz, 1H), 3.43 (dd, J =
8.5, 2.0 Hz, 1H), 3.39 (s, 3H), 3.34 (dd, J = 11.0, 4.0 Hz, 1H), 3.24 (dd, J
4.11. N-tert-Butyloxycarbonyl-3-O-(4,6-di-O-benzylidenyl-3-O-tert-
butyldiphenylsilyl-2-azido-2-deoxy-α-D-galactopyranosyl)-D-Threonine
allyl ester (10d)
Prepared from 5 (86 mg, 0.135 mmol) and 8d (28 mg, 0.114 mmol)
following the general Procedure. The residue was purified by column
8

X.-Y. Liang et al.
Carbohydrate Research 500 (2021) 108237
= 12.0, 1.5 Hz, 1H), 3.11 (s, 1H), 1.08 (s, 9H); 13C NMR (150 MHz,
CDCl3): δ 138.6, 138.0, 137.9, 137.8, 136.0, 135.9, 134.2, 132.9, 130.0,
129.8, 128.8, 128.5, 128.4, 128.4, 128.1, 128.1, 128.0, 127.9, 127.6,
127.5, 127.4, 127.0, 126.1, 100.4, 98.4, 97.9, 81.9, 80.5, 77.2, 75.6,
74.9, 73.3, 73.2, 72.4, 69.5, 69.4, 69.0, 69.0, 63.0, 60.6, 55.4, 26.8,
4.16. Methyl 4,6-di-O-benzylidenyl-3-O-tert-butyldiphenylsilyl-2-azido-
2-deoxy-α-D-galactopyranosyl-(1 → 3)-2,5-di-O-benzoyl-α-D-
arabinofuranoside (10i)
Prepared from 5 (108 mg, 0.170 mmol) and 8i (52 mg, 0.140 mmol)
following the general Procedure. The residue was purified by column
chromatography (Petroleum ether–EtOAc, 8:1) to afford compound 10i
19.3; For β: Rf 0.2 (8:1, petroleum ether–EtOAc); [α]D 8.2 (c 0.6, CHCl3);
1H NMR (600 MHz, CDCl3): δ 7.80–7.76 (m, 4H), 7.53–7.15 (m, 26H),
5.11 (t, J = 5.0 Hz, 2H), 4.82 (d, J = 12.5 Hz, 1H), 4.75 (d, J = 11.0 Hz,
1H), 4.64 (dd, J = 12.0, 5.0 Hz, 2H), 4.59 (d, J = 4.0 Hz, 1H), 4.34 (d, J
= 11.5 Hz, 1H), 4.13 (d, J = 12.5 Hz, 1H), 4.05 (dd, J = 12.0, 1.5 Hz,
1H), 3.99 (dd, J = 11.0, 3.0 Hz, 1H), 3.95–3.89 (m, 2H), 3.82–3.75 (m,
3H), 3.55–3.49 (m, 2H), 3.40 (dd, J = 10.0, 3.5 Hz, 1H), 3.39 (s, 3H),
3.29 (d, J = 3.5 Hz, 1H), 2.50 (s, 1H), 1.08 (s, 9H); 13C NMR (150 MHz,
CDCl3): δ 139.2, 138.5, 138.1, 138.1, 136.0, 135.9, 134.1, 132.9, 130.0,
129.9, 128.8, 128.5, 128.4, 128.3, 128.1, 127.8, 127.8, 127.7, 127.6,
127.5, 127.2, 126.3, 101.5, 100.6, 98.3, 80.4, 79.3, 77.4, 77.2, 75.9,
74.5, 73.6, 73.2, 73.2, 69.7, 68.6, 66.1, 65.0, 55.4, 26.8, 19.4;
HRMS–ESI–TOF calcd for [M+Na]+ C57H63N3NaO10Si: 1000.4180.
Found: 1000.4179.
as a light syrup (92 mg, yield of 74.4%, α-only). Rf 0.3 (6:1, petroleum
ether–EtOAc); [
α]
D 102.4 (c 0.5, CHCl3); 1H NMR (600 MHz, CDCl3): δ
7.97 (t, J = 8.4 Hz, 4H), 7.90 (d, J = 6.6 Hz, 2H), 7.76 (d, J = 6.6 Hz,
2H), 7.59 (t, J = 7.8 Hz, 1H), 7.53–7.35 (m, 14H), 7.30 (q, J = 15.6 Hz,
1H), 5.36 (d, J = 4.2 Hz, 2H), 5.09 (s, 1H), 5.01 (s, 1H), 4.55 (dd, J =
12.0, 2.4 Hz, 1H), 4.44–4.42 (m, 1H), 4.27 (s, 2H), 4.25 (dd, J = 10.8,
3.6 Hz, 1H), 3.96 (d, J = 12.6 Hz, 1H), 3.92 (dd, J = 10.8, 3.6 Hz, 1H),
3.59 (d, J = 12.0 Hz, 1H), 3.49 (d, J = 3.0 Hz, 1H), 3.45 (s, 3H), 3.32 (s,
1H), 1.08 (s, 9H); 13C NMR (150 MHz, CDCl3): δ 166.2, 165.4, 137.7,
13.98.0, 135.89, 134.2, 133.5, 133.3, 132.8, 129.97, 129.86, 129.82,
129.64, 129.44, 129.14, 128.87, 128.51, 128.44, 128.12, 127.86,
127.57, 126.1, 106.9, 100.5, 98.6, 82.3, 81.5, 79.9, 77.3, 77.1, 76.8,
75.3, 69.3, 69.0, 63.5, 63.1, 60.3, 54.8, 26.8, 19.3; HRMS–ESI–TOF
calcd for [M+Na]+ C49H51N3NaO11Si: 908.3191. Found 908.3188.
4.14. (2-Trimethylsilyl)-ethyl 4,6-di-O-benzylidenyl-3-O-tert-
butyldiphenylsilyl-2-azido-2-deoxy-
α
,β-D-galactopyranosyl-(1 → 3)-4,6-
4.17. Methyl 4,6-di-O-benzylidenyl-3-O-tert-butyldiphenylsilyl-2-azido-
di-O-benzylidenyl-2-azido-2-deoxy-β-D-glucopyranoside (10g)
2-deoxy-α-D-galactopyranosyl-(1 → 4)-2:3-O-isopropylidene-α-L-
rhamnopyranoside (10j)
Prepared from 5 (84 mg, 0.132 mmol) and 8g (43 mg, 0.109 mmol)
following the general Procedure. The residue was purified by column
chromatography (Petroleum ether–EtOAc, 12:1) to afford compound
Prepared from 5 (105 mg, 0.165 mmol) and 8j (30 mg, 0.138 mmol)
following the general Procedure. The residue was purified by column
chromatography (Petroleum ether–EtOAc, 8:1) to afford compound 10j
10g as a light syrup (70 mg, yield of 70.7%, α-only). Rf 0.3 (8:1, pe-
troleum ether–EtOAc); [
α]
77.7 (c 1.3, CHCl3); 1H NMR (500 MHz,
as a light syrup (87 mg, yield of 86.4%, α:β = 7:1). For α: Rf 0.3 (6:1,
D
CDCl3): δ 7.79–7.75 (m, 4H), 7.53–7.36 (m, 14H), 7.29 (t, J = 8.0 Hz,
2H), 5.61 (d, J = 3.5 Hz, 1H), 5.58 (s, 1H), 5.15 (s, 1H), 4.40 (d, J = 8.0
Hz, 1H), 4.35 (q, J = 5.0 Hz, 1H), 4.24 (dd, J = 10.5, 3.5 Hz, 1H), 4.12
(dd, J = 12.5, 1.0 Hz, 1H), 3.83 (dd, J = 10.5, 3.5 Hz, 1H), 3.80–3.61 (m,
7H), 3.39 (td, J = 10.0, 5.0 Hz, 1H), 3.25 (dd, J = 10.0, 8.0 Hz, 1H), 1.10
(s, 9H), 1.06–1.02 (m, 2H), 0.05 (s, 9H); 13C NMR (125 MHz, CDCl3): δ
137.8, 136.8, 136.0, 135.8, 134.3, 132.7, 130.1, 129.8, 128.8, 128.3,
128.1, 127.8, 127.5126.1, 125.9, 102.1, 101.4, 100.4, 98.8, 81.7, 77.2.
75.7, 74.2, 69.2, 68.9, 68.5, 68.3, 65.9, 65.2, 63.2, 60.1, 26.8, 19.3,
18.3, ꢀ 1.4; HRMS–ESI–TOF calcd for [M+Na]+ C47H58N6NaO9Si2:
929.3702. Found: 929.3696.
petroleum ether–EtOAc); [
α
]D 100.1 (c 0.7, CHCl3); 1H NMR (600 MHz,
CDCl3): δ 7.76 (t, J = 7.2 Hz, 4H), 7.49–7.46 (m, 3H), 7.42–7.35 (m, 7H),
7.27 (t, J = 7.8 Hz, 1H), 5.13 (d, J = 3.0 Hz, 1H), 5.01 (s, 1H), 4.83 (s,
1H), 4.28 (dd, J = 10.8, 3.6 Hz, 1H), 4.05 (s, 1H), 4.04 (d, J = 6.6 Hz,
1H), 3.92–3.90 (m, 2H), 3.76 (s, 1H), 3.72 (d, J = 12.0 Hz, 1H), 3.69 (q,
J = 10.2 Hz, 1H), 3.51 (d, J = 3.0 Hz, 1H), 3.37 (t, J = 4.8 Hz, 4H), 1.44
(s, 3H), 1.36 (d, J = 6.6 Hz, 3H), 1.26 (s, 3H), 1.08 (s, 9H); 13C NMR
(150 MHz, CDCl3): δ 137.8, 135.9, 135.89, 134.3, 132.9, 130.0, 129.8,
128.8, 128.1, 127.8, 127.5, 126.1, 109.0, 100.4, 99.3, 97.7, 79.9, 77.2,
77.0, 76.9, 76.8, 76.1, 75.3, 69.6, 69.1, 65.0, 62.7, 61.3, 54.9, 31.9,
29.7, 28.1, 26.9, 26.4, 22.7, 19.3, 17.5, 14.1; For β: Rf 0.25 (6:1, pe-
troleum ether–EtOAc); [
α
]
11.3 (c 0.7, CHCl3); 1H NMR (600 MHz,
CDCl3): δ 7.78 (qd, J = 7.8D1.2 Hz, 4H), 7.54 (dd, J = 8.4, 1.8 Hz, 2H),
7.48–7.45 (m, 1H), 7.43–7.38 (m, 7H), 7.29 (t, J = 7.8 Hz, 2H), 5.10 (s,
1H), 4.85 (s, 1H), 4.68 (d, J = 8.4 Hz, 1H), 4.27 (t, J = 6.6 Hz, 1H),
4.11–4.09 (m, 2H), 3.80 (q, J = 10.2 Hz, 1H), 3.74 (dd, J = 12.0, 1.8 Hz,
1H), 3.68 (q, J = 6.6 Hz, 2H), 3.64 (dd, J = 10.2, 3.6 Hz, 1H), 3.38 (s,
1H), 3.37 (s, 3H), 3.01 (s, 1H), 1.44 (s, 3H), 1.32 (d, J = 5.4 Hz, 6H),
1.06 (s, 9H); 13C NMR (150 MHz, CDCl3): δ 138.0, 136.1135.9, 134.2,
132.8, 129.89, 129.80, 128.9, 128.2, 127.8, 127.6, 126.2, 109.1, 100.7,
100.0, 99.8, 97.9, 78.1, 77.8, 77.2, 77.0, 76.8, 76.1, 74.6, 72.8, 69.0,
66.2, 64.5, 64.2, 54.8, 31.9, 29.7, 29.4, 27.8, 26.8, 26.4, 22.7, 19.4,
17.7, 14.1, 1.0; HRMS–ESI–TOF calcd for [M+Na]+ C39H49N3NaO9Si:
754.3136. Found: 754.3136.
4.15. 4,6-Di-O-benzylidenyl-3-O-tert-butyldiphenylsilyl-2-azido-2-deoxy-
α
-D-galactopyranosyl-(1 → 2)-1,3,4-tri-O-benzoyl-α-D-ribofuranose (10h)
Prepared from 5 (84 mg, 0.132 mmol) and 8h (52 mg, 0.113 mmol)
following the general Procedure. The residue was purified by column
chromatography (Petroleum ether–EtOAc, 8:1) to afford compound 10h
as a light syrup (87 mg, yield of 79.8%, α-only). Rf 0.2 (8:1, petroleum
ether–EtOAc); [
α]
D 147.0 (c 0.5, CHCl3); 1H NMR (600 MHz, CDCl3): δ
8.22 (dd, J = 8.4, 1.2 Hz, 2H), 8.05 (dd, J = 8.4, 1.2 Hz, 2H), 8.02 (dd, J
= 8.4, 1.8 Hz, 2H), 7.65 (t, J = 7.8 Hz, 1H), 7.59–7.53 (m, 4H), 7.49 (d,
J = 6.6 Hz, 2H), 7.47 (td, J = 8.4, 3.6 Hz, 4H), 7.39 (dd, J = 7.2, 3.6 Hz,
2H), 7.34–7.27 (m, 7H), 7.17 (t, J = 7.8 Hz, 2H), 7.12 (t, J = 7.8 Hz, 2H),
6.82 (d, J = 4.2 Hz, 1H), 5.60 (dd, J = 6.6, 1.8 Hz, 1H), 5.21 (d, J = 3.6
Hz, 1H), 4.86 (s, 1H), 4.80 (q, J = 5.4 Hz, 1H), 4.66 (q, J = 6.6 Hz, 1H),
4.60 (t, J = 3.0 Hz, 2H), 4.09 (dd, J = 10.2, 3.0 Hz, 1H), 3.89 (dd, J =
10.2, 3.6 Hz, 1H), 3.87 (dd, J = 12.6, 1.2 Hz, 1H), 3.50 (dd, J = 12.6, 1.2
Hz, 1H), 3.44 (s, 1H), 3.17 (d, J = 2.4 Hz, 1H), 0.9 (s, 9H); 13C NMR
(150 MHz, CDCl3): δ 166.1, 165.98, 165.6, 137.6, 135.6, 135.5, 134.1,
133.6, 133.5, 133.3, 133.2, 130.1, 129.95, 129.82, 129.80, 129.75,
129.56, 129.24, 128.8, 128.7, 128.5, 128.3, 128.1, 127.6, 127.5, 126.1,
100.4, 98.5, 94.0, 82.5, 77.25, 77.0, 76.8, 74.8, 74.2, 71.4, 69.4, 68.9,
64.1, 63.5, 60.7, 26.8, 19.3; HRMS–ESI–TOF calcd for [M+Na]+
C55H53N3NaO12Si: 998.3296. Found: 998.3305.
4.18. Methyl 4,6-di-O-benzylidenyl-3-O-benzoyl-2-azido-2-deoxy-
α,β-D-
galactopyranosyl-(1 → 5)-2,3-di-O-benzoyl- -D-arabinofuranoside (11)
α
A mixture of 6 (73 mg, 0.145 mmol), 8c (44 mg, 0.120 mmol) and
freshly activated 4 Å molecular sieves (117 mg) in dry CH2Cl2 (1.5 mL)
was cooled to 0 ◦C. The suspension was stirred for 15 min, then NIS (49
mg, 0.217 mmol) and TfOH (1.3 μL, 015 mmol) were added. The reac-
tion mixture was stirred for 5 min at the same temperature. The reaction
mixture was gradually warmed to rt and was stirred for 1–2 h at the
same temperature. The mixture was quenched with Et3N and was
diluted with CH2Cl2 and added Na2S2O3, filtered through celite and
9

X.-Y. Liang et al.
Carbohydrate Research 500 (2021) 108237
concentrated in vacuo. The crude material was quickly purified by col-
4.20. 4,6-Di-O-benzylidenyl-3-O-benzyl-2-azido-2-deoxy-
α,β-D-
umn chromatography (4:1, petroleum ether–EtOAc) to afford compound
galactopyranosyl-(1 → 2)-1,3,4-tri-O-benzoyl- -D-ribofuranose (13)
α
11 as a colorless syrup (80 mg, yield of 89.8%,α:β = 1:1). For α: Rf 0.45
(3:1, petroleum ether–EtOAc), 1H NMR (600 MHz, CDCl3): δ 8.09–8.06
(m, 6H), 7.61–7.58 (m, 2H), 7.48–7.45 (m, 7H), 7.41–7.38 (m, 2H),
7.35–7.33 (m, 3H), 5.57–5.55 (m, 1H), 5.54 (s, 1H), 5.53 (d, J = 1.8 Hz,
1H), 5.52–5.50 (m, 1H), 5.26 (d, J = 3.6 Hz, 1H), 5.15 (s, 1H), 4.66 (d, J
= 3.6 Hz, 1H), 4.45–4.43 (m, 1H), 4.33 (dd, J = 6.6, 1.8 Hz, 1H)
4.20–4.17 (m, 1H), 4.16 (dd, J = 11.4, 5.4 Hz, 1H), 4.11–4.04 (m, 2H),
4.01–3.99 (m, 1H), 3.49 (s, 3H), 13C NMR (150 MHz, CDCl3): δ 165.9,
165.8, 165.6, 137.6, 133.6, 133.48, 133.46, 129.97, 129.96, 129.94,
129.4, 129.11, 129.05, 129.95, 128.52, 128.49, 128.1, 126.0, 106.8,
100.6, 98.7, 82.3, 81.2, 77.5, 77.3, 77.1, 76.8, 73.5, 70.4, 69.2, 67.6,
62.8, 57.8, 55.0. For β: Rf 0.20 (3:1, petroleum ether–EtOAc), 1H NMR
(600 MHz, CDCl3): δ 8.08–8.07 (m, 6H), 7.60–7.54 (m, 3H), 7.48–7.42
(m, 8H), 7.36–7.33 (m, 3H), 5.52 (s, 1H), 5.50–4.49 (m, 2H), 5.16 (s,
1H), 5.01 (dd, J = 10.8, 3.6 Hz, 1H), 4.67 (d, J = 7.8 Hz, 1H), 4.52–4.50
(m, 1H), 4.49 (d, J = 3.6 Hz, 1H), 4.44–4.44 (m, 1H), 4.37 (d, J = 1.2 Hz,
1H), 4.14 (dd, J = 10.8, 8.4 Hz, 1H), 4.10–4.07 (m, 1H), 4.00–3.97 (m,
1H), 3.59 (s, 1H), 3.48 (s, 3H), 13C NMR (150 MHz, CDCl3): δ 160.0,
165.9, 165.5, 137.5, 133.54, 133.47, 133.46, 130.0, 129.9, 129.3,
129.2, 129.0, 128.51, 128.50, 128.47, 128.1, 126.2, 106.8, 102.5,
100.8, 82.3, 81.2, 77.6, 77.3, 77.0, 76.8, 72.82, 72.76, 69.4, 68.9, 66.5,
60.5, 54.9, 32.0, 31.5, 30.2, 29.7, 29.4, 22.7, 14.2; HRMS–ESI–TOF
calcd for [M+Na]+ C40H37N3NaO12: 774.2275. Found: 774.2286.
A mixture of 7 (120 mg, 0.245 mmol), 8h (94 mg, 0.204 mmol) and
freshly activated 4 Å molecular sieves (214 mg) in dry CH2Cl2 (2.5 mL)
was cooled to ꢀ 20 ◦C. The suspension was stirred for 15 min, then NIS
(83 mg, 0.368 mmol) and TfOH (2.2 μL, 025 mmol) were added. The
reaction mixture was stirred for 5 min at the same temperature. The
reaction mixture was gradually warmed to 0 ◦C and was stirred for 2 h at
the same temperature. The mixture was quenched with Et3N and was
diluted with CH2Cl2 and added Na2S2O3, filtered through celite and
concentrated in vacuo. The crude material was quickly purified by col-
umn chromatography (5:1, petroleum ether–EtOAc) to afford compound
13 as a colorless syrup (128 mg, yield of 76.2%, a complex product). Rf
0.40 (4:1, petroleum ether–EtOAc); 1H NMR (600 MHz, CDCl3): δ 8.23
(dd, J = 8.4, 1.2 Hz, 2H), 8.15 (dd, J = 7.8, 1.2 Hz, 2H), 8.09–8.01 (m,
7H), 7.96 (dd, J = 7.8, 1.2 Hz, 1H), 7.90 (dd, J = 8.4, 1.2 Hz, 1H),
7.62–7.32 (m, 28H), 7.23–7.21 (m, 3H), 7.17–7.15 (m, 2H), 6.84 (d, J =
4.2 Hz, 1H), 5.82 (td, J = 8.4, 4.2 Hz, 1H), 5.78 (dd, J = 7.2, 2.4 Hz, 1H),
5.38 (s, 1H), 5.17 (d, J = 3.0 Hz, 1H), 4.93 (dd, J = 6.0, 3.6 Hz, 1H), 4.74
(dd, J = 4.2, 3.0 Hz, 1H), 4.73 (d, J = 3.0 Hz, 1H), 4.63 (d, J = 3.6 Hz,
2H), 4.25 (s, 2H), 4.08 (dd, J = 12.6, 1.2 Hz, 2H), 3.95 (dd, J = 12.6, 1.8
Hz, 1H), 3.84 (dd, J = 10.8, 3.6 Hz, 1H), 3.79 (s, 1H), 3.60 (dd, J = 10.8,
3.6 Hz, 1H); 13C NMR (150 MHz, CDCl3): δ 166.6, 166.5, 166.2, 166.0,
165.62, 165.58, 165.47, 165.37, 165.26, 137.71, 137.48, 133.78,
133.66, 133.65, 133.58, 133.53, 133.45, 133.39, 133.36, 133.23, 130.1,
130.0, 129.84, 129.80, 129.79, 129.76, 129.75, 129.6, 129.39, 129.32,
129.19, 129.0, 128.9, 129.7, 128.6, 128.59, 128.56, 128.51, 128.50,
128.44, 128.41, 128.33, 128.29, 128.21, 127.8, 127.6, 126.2, 100.9,
100.5, 97.7, 95.8, 94.1, 81.7, 79.6, 79.3, 77.3, 77.0, 76.9, 76.2, 74.7,
73.1, 72.96, 72.4, 71.9, 71.8, 71.5, 69.1, 65.2, 64.18, 64.14, 63.8, 58.1,
31.96, 31.5, 30.2, 29.73, 29.69, 29.4, 26.9, 22.7, 14.2.
4.19. Methyl 4,6-di-O-benzylidenyl-3-O-benzyl-2-azido-2-deoxy-
α,β-D-
galactopyranosyl-(1 → 5)-2,3-di-O-benzoyl- -D-arabinofuranoside (12)
α
A mixture of 7 (98 mg, 0.200 mmol), 8c (62 mg, 0.167 mmol) and
freshly activated 4 Å molecular sieves (160 mg) in dry CH2Cl2 (2 mL)
was cooled to ꢀ 20 ◦C. The suspension was stirred for 15 min, then NIS
(68 mg, 0.300 mmol) and TfOH (1.8 μL, 020 mmol) were added. The
reaction mixture was stirred for 5 min at the same temperature. The
reaction mixture was gradually warmed to 0 ◦C and was stirred for 1–2 h
at the same temperature. The mixture was quenched with Et3N and was
diluted with CH2Cl2 and added Na2S2O3, filtered through celite and
concentrated in vacuo. The crude material was quickly purified by col-
umn chromatography (3:1, petroleum ether–EtOAc) to afford compound
4.21. Methyl 4,6-di-O-benzylidenyl-3-O-benzoyl-2-azido-2-deoxy-
α-D-
galactopyranosyl-(1 → 3)-2,5-di-O-benzoyl- -D-arabinofuranoside (14)
α
A mixture of 6 (80 mg, 0.159 mmol), 8i (49 mg, 0.133 mmol) and
freshly activated 4 Å molecular sieves (129 mg) in dry CH2Cl2 (1.6 mL)
was cooled to 0 ◦C. The suspension was stirred for 15 min, then NIS (53
12 as a colorless syrup (105 mg, yield of 85.5%, α:β = 2:3). For α: Rf 0.65
mg, 0.238 mmol) and TfOH (1.4 μL, 016 mmol) were added. The reac-
(2:1, petroleum ether–EtOAc), 1H NMR (600 MHz, CDCl3): δ 8.11 (dd, J
= 8.4, 1.2 Hz, 2H), 8.08 (dd, J = 7.8, 1.2 Hz, 2H), 7.62–7.59 (m, 1H),
7.55–7.52 (m, 1H), 7.51–7.43 (m, 6H), 7.37–7.28 (m, 8H), 5.50–5.49
(m, 2H), 5.44 (s, 1H), 5.16 (s, 1H), 5.14 (d, J = 3.6 Hz, 1H), 4.58 (dd, J
= 21, 12 Hz, 2H), 4.43–4.40 (m, 1H), 4.26 (dd, J = 12, 1.2 Hz, 1H), 4.20
(d, J = 3.0 Hz, 1H), 4.06 (dd, J = 10.8, 5.4 Hz, 1H), 4.02–3.97 (m, 3H),
3.96 (dd, J = 12, 3.0 Hz, 1H), 3.84 (s, 1H), 3.47 (s, 3H), 13C NMR (150
MHz, CDCl3): δ 165.8, 165.5, 138.0, 137.6, 133.62, 133.57, 129.94,
129.89, 129.2, 129.1, 129.0, 128.6, 128.5, 128.8, 128.2, 127.7, 127.6,
126.2, 106.8, 100.9, 98.7, 82.3, 81.1, 77.4, 77.2, 77.0, 76.8, 74.9, 73.0,
71.2, 69.4, 67.1, 63.0, 58.8, 54.9, 31.4, 30.2, 1.03. For β: Rf 0.35 (2:1,
tion mixture was stirred for 5 min at the same temperature. The reaction
mixture was gradually warmed to r.t. and was stirred for 2 h at the same
temperature. The mixture was quenched with Et3N and was diluted with
CH2Cl2 and added Na2S2O3, filtered through celite and concentrated in
vacuo. The crude material was quickly purified by column chromatog-
raphy (5:1, petroleum ether–EtOAc) to afford compound 14 as a color-
less syrup (18 mg, yield of 18.2%,
α-only). Rf 0.35 (3:1, petroleum
ether–EtOAc); 1H NMR (600 MHz, CDCl3): δ 8.11 (dd, J = 7.8, 1.2 Hz,
2H), 8.03 (dd, J = 8.4, 1.2 Hz, 2H), 7.99 (dd, J = 8.4, 1.2 Hz, 2H),
7.61–7.58 (m, 2H), 7.55–7.52 (m, 1H), 7.48–7.40 (m, 6H), 7.34–7.31
(m, 5H), 5.58–5.55 (m, 2H), 5.50 (s, 1 H), 5.38 (d, J = 0.6 Hz, 1H), 5.16
(s, 1 H), 4.65 (d, J = 3.6 Hz, 2H), 4.61 (d, J = 3.0 Hz, 1H), 4.51–4.49 (s,
1H), 4.38 (d, J = 6.0 Hz, 1H), 4.20–4.16 (m, 2H), 3.97 (dd, J = 12.6, 1.2
Hz, 1H), 3.87 (s, 1H), 3.47 (s, 3H), 13C NMR (150 MHz, CDCl3): δ 166.3,
166.1, 165.4, 137.4, 133.5, 133.3, 130.0, 129.8, 129.7, 129.4, 129.3,
129.1, 129.0, 128.52, 128.48, 128.1, 126.0, 106.9, 100.6, 98.1, 82.3,
81.8, 80.2, 77.2, 77.0, 76.8, 73.4, 69.9, 69.0, 63.3, 63.1, 57.1, 54.9,
1
petroleum ether–EtOAc), H NMR (600 MHz, CDCl3): δ 8.07–8.06 (m,
4H), 7.59–7.52 (m, 4H), 7.46–7.29 (m, 12H), 5.51 (dd, J = 6, 1.8 Hz,
1H), 5.49 (d, J = 1.8 Hz, 1H), 5.47 (s, 1H), 5.45 (s, 1H), 4.75 (dd, J =
14.4, 12.6 Hz, 2H), 4.88 (dd, J = 6.0, 3.0 Hz, 1H), 4.46 (d, J = 8.4 Hz,
1H), 4.39 (dd, J = 13.2, 3.0 Hz, 1H), 4.30 (dd, J = 12.6, 1.2 Hz, 1H),
4.07 (d, J = 3.0 Hz, 1H), 4.00 (dd, J = 12.0, 1.8 Hz, 1H), 3.94–3.90 (m,
2H), 3.47 (s, 3H), 3.42 (dd, J = 10.2, 3.6 Hz, 1H), 3.33 (s, 1H), 13C NMR
(150 MHz, CDCl3): δ 165.9, 165.5, 137.7, 137.6, 133.4, 129.95, 129.88,
129.21, 129.17, 129.0, 128.5, 128.44, 128.43, 128.2, 127.9, 127.8,
126.4, 106.7, 102.5, 101.1, 82.4, 81.2, 77.8, 77.5, 77.2, 77.0, 76.8, 72.4,
71.6, 69.2, 69.1, 66.6, 61.9, 54.9; HRMS–ESI–TOF calcd for [M+Na]+
C40H39N3NaO11: 760.2482. Found: 760.2488.
31.5, 29.8. HRMS–ESI–TOF calcd for [M+Na]+ C40H37N3NaO12
:
774.2275. Found: 774.2277.
4.22. Methyl 4,6-di-O-benzylidenyl-3-O-benzyl-2-azido-2-deoxy-
α-D-
galactopyranosyl-(1 → 3)-2,5-di-O-benzoyl- -D-arabinofuranoside (15)
α
A mixture of 7 (88 mg, 0.180 mmol), 8i (56 mg, 0.50 mmol) and
freshly activated 4 Å molecular sieves (144 mg) in dry CH2Cl2 (1.8 mL)
was cooled to ꢀ 20 ◦C. The suspension was stirred for 15 min, then NIS
10

X.-Y. Liang et al.
Carbohydrate Research 500 (2021) 108237
(61 mg, 0.270 mmol) and TfOH (1.6
μ
L, 0.018 mmol) were added. The
4.94 (d, J = 2.0 Hz, 1H), 4.39 (dd, J = 8.5, 5.0 Hz, 1H), 4.25–4.22 (m,
1H), 4.13 (dd, J = 11.0, 5.0 Hz, 1H), 4.02 (td, J = 6.0, 2.5 Hz, 1H),
3.90–3.86 (m, 2H), 3.78–3.71 (m, 2H), 3.53 (dt, J = 9.5, 6.5 Hz, 1H),
3.24 (t, J = 7.0 Hz, 2H), 2.76–2.73 (m, 2H), 2.64–2.60 (m, 2H), 2.14 (s,
3H), 1.67–1.54 (m, 4H), 1.43–1.28 (m, 8H), 1.03 (s, 9H), 0.91 (s, 9H);
13C NMR (125 MHz, CDCl3): δ 206.3, 172.9, 165.9, 165.4, 133.5, 130.0,
129.9, 129.2, 129.2, 128.6, 128.5, 105.6, 105.0, 85.4, 84.7, 81.9, 81.6,
77.4, 77.2, 76.4, 67.6, 65.8, 62.2, 51.4, 37.9, 29.7, 29.5, 29.3, 29.1,
28.8, 27.8, 26.7, 26.1; HRMS–ESI–TOF calcd for [M+Na]+
C37H43N3NaO13Si: 764.3007. Found: 764.3003.
reaction mixture was stirred for 5 min at the same temperature. The
reaction mixture was gradually warmed to 0 ◦C and was stirred for 1–2 h
at the same temperature. The mixture was quenched with Et3N and was
diluted with CH2Cl2 and added Na2S2O3, filtered through celite and
concentrated in vacuo. The crude material was quickly purified by col-
umn chromatography (3:1, petroleum ether–EtOAc) to afford compound
15 as a colorless syrup (53 mg, yield of 47.8%, α-only). Rf 0.35(2:1,
petroleum ether–EtOAc); 1H NMR (600 MHz, CDCl3): δ 8.02 (dd, J = 7.8,
1.2 Hz, 2H), 7.99 (dd, J = 8.4, 1.2 Hz, 2H), 7.60–7.57 (m, 1H),
7.55–7.53 (m, 1H), 7.49 (dd, J = 7.8, 1.8 Hz, 2H), 7.43–7.40 (m, 4H),
7.36–7.29 (m, 8H), 5.43 (s, 1H), 5.39 (d, J = 3.0 Hz, 2H), 5.13 (s, 1H),
4.78 (dd, J = 28.2, 11.4 Hz, 2H), 4.64 (dd, J = 12.0, 3.0 Hz, 1H), 4.59
(dd, J = 12.6, 4.8 Hz, 1H), 4.45–4.43 (m, 1H), 4.35 (d, J = 6.0 Hz, 1H),
4.21 (d, J = 3.0 Hz, 1H), 4.15 (dd, J = 12.6, 1.2 Hz, 1H), 4.04 (dd, J =
10.8, 3.6 Hz, 1H), 3.97 (dd, J = 10.8, 3.6 Hz, 1H), 3.92 (dd, J = 12.6, 1.2
Hz, 1H), 3.67 (s, 1H), 3.47 (s, 3H), 13C NMR (150 MHz, CDCl3): δ 166.3,
165.4, 137.9, 137.5, 133.5, 133.4, 129.8, 129.7, 129.4, 129.1, 129.0,
128.51, 128.47, 128.43, 128.2, 127.9, 127.7, 126.2, 107.0, 100.9, 99.3,
82.3, 81.8, 80.0, 77.2, 77.0, 74.4, 72.9, 71.3, 69.2, 63.5, 63.2, 58.2,
4.25. Toluene 5-O-(2,2,2-trichloroethoxy)-carbonyl-2,3-di-O-benzoyl-
α
-D-arabinofuranoside (20)
[20]
To a solution of 2,3-di-O-benzoyl-1-thio-α-D-arabinofuranoside
(1.53 g, 3.30 mmol) in dry CH2Cl2 (6.6 mL) was added pyridine (0.37
mL, 3.00 mmol) and Troc-Cl (0.55 mL, 3.96 mmol). The reaction
mixture was stirred at 0 ◦C for 1 h. The resulting mixture was added H2O
and extracted with CH2Cl2. The organic layer was washed with 1 N HCl,
saturated aqueous NaHCO3 and brine, dried over Na2SO4, filtered and
concentrated in vacuo. The residue was purified by column chroma-
tography (6:1, petroleum ether–EtOAc) to afford compound 20 as a
55.0, 31.5, 30.2; HRMS–ESI–TOF calcd for [M+Na]+ C40H39N3NaO11
:
760.2482. Found: 760.2471.
yellow syrup (1.99 g, 88%). Rf 0.4 (4:1, petroleum ether–EtOAc); [α]
D
4.23. 8-Azidooctyl 3,5-O-(di-tert-butylsilylene)-2-O-levulinoyl-
α
-D-
79.6 (c 1.1, CHCl3); 1H NMR (500 MHz, CDCl3): δ 8.13 (dd, J = 8.5, 1.0
Hz, 2H), 8.09 (dd, J = 8.5, 1.0 Hz, 2H), 7.64–7.44 (m, 8H), 7.15 (d, J =
8.0 Hz, 2H), 5.73 (t, J = 1.5 Hz, 1H), 5.52 (dt, J = 4.5, 1.0 Hz, 1H), 4.80
(d, J = 12.0 Hz, 1H), 4.76 (d, J = 12.0 Hz, 1H), 4.76–4.70 (m, 2H), 4.70
(dd, J = 12.0, 5.0 Hz, 1H), 2.34 (s, 3H), 1.40 (s, 3H), 1.34 (s, 3H), 1.05 (s,
9H); 13C NMR (125 MHz, CDCl3): δ 165.7, 165.3, 153.9, 138.2, 133.7,
133.6, 132.9, 130.1, 130.0, 129.9, 129.9, 129.8, 129.6, 94.3, 92.0, 81.9,
81.1, 77.9, 77.2, 77.0, 76.4, 67.4, 21.2; HRMS–ESI–TOF calcd for [M +
NH4]+ C29H29Cl3NO8S: 656.0679. Found: 656.0672.
arabinofuranosyl-(1 → 5)-2,3-di-O-benzoyl- -D-arabinofuranoside (18)
α
A mixture of thioglycoside 16 (1.151 g, 2.330 mmol) and acceptor 17
(990 mg, 1.937 mmol), and freshly activated 4 Å molecular sieves
(2.150 g) in dry CH2Cl2 (23 mL) was cooled to ꢀ 30 ◦C. The suspension
was stirred for 15 min, then NIS (678 mg, 3.01 mmol), TfOH (10 μL,
0.113 mmol) was added. The reaction mixture was stirred for 1 h
ꢀ 30 ◦C. The reaction mixture was gradually warmed to 0 ◦C and
quenched with Et3N. The mixture was diluted with CH2Cl2 and added
Na2S2O3, filtered through celite and concentrated in vacuo. The crude
material was quickly purified by column chromatography (Petroleum
ether–EtOAc, 5:1) to give the product 18 (1.555 g, yield of 91.2%) as a
4.26. 8-Azidooctyl 3,5-di-O-[5-O-(2,2,2-trichloroethoxy)-carbonyl-2,3-
di-O-benzoyl-α-D-arabinofuranosyl]-2-O-levulinoyl-α-D-arabinofuranosyl-
(1 → 5)-2,3-di-O-benzoyl-α-D-arabinofuranoside (21)
yellow syrup. For α: Rf 0.25 (4:1, petroleum ether–EtOAc); [α]D 11.8 (c
1.8, CHCl3); 1H NMR (500 MHz, CDCl3): δ 8.09–8.06 (m, 4H), 7.60–7.50
(m, 2H), 7.48 (dd, J = 15.5, 8.0 Hz, 4H), 5.46 (s, 1H), 5.46 (d, J = 4.0 Hz,
1H), 5.21 (s, 1H), 5.16 (dd, J = 6.5, 2.0 Hz, 1H), 5.00 (d, J = 2.0 Hz, 1H),
4.46 (dd, J = 9.5, 4.5 Hz, 1H), 4.35–4.32 (m, 1H), 4.12–4.06 (m, 2H),
4.04 (dd, J = 11.0, 5.5 Hz, 1H), 3.93–3.90 (m, 1H), 3.89 (dd, J = 11.0,
4.0 Hz, 1H), 3.79 (dt, J = 9.5, 7.0 Hz, 1H), 3.54 (dt, J = 9.5, 6.0 Hz, 1H),
3.24 (t, J = 7.0 Hz, 2H), 3.20 (t, J = 6.5 Hz, 2H), 2.76–2.73 (m, 2H),
2.58–2.55 (m, 2H), 2.18 (s, 3H), 2.04 (dd, J = 7.5, 5.5 Hz, 2H),
1.67–1.54 (m, 4H), 1.42–1.26 (m, 8H); 13C NMR (125 MHz, CDCl3): δ
206.2, 171.8, 165.6, 165.5, 133.4, 133.3, 129.9, 129.9, 129.5, 129.3,
128.5, 128.4, 106.6, 105.7, 82.9, 81.9, 81.4, 80.4, 77.6, 77.2, 73.6, 67.8,
67.5, 67.4, 51.5, 37.9, 29.8, 29.5, 29.3, 29.1, 28.8, 27.9, 27.4, 27.0,
26.7, 26.1, 22.6, 20.0; HRMS–ESI–TOF calcd for [M+Na]+
C45H63N3NaO13Si: 904.4028. Found: 904.4034.
A mixture of thioglycoside 20 (795 mg, 1.246 mmol) and acceptor 19
(438 mg, 0.591 mmol), and freshly activated 4 Å molecular sieves
(1.240 g) in dry CH2Cl2 (13 mL) was cooled to ꢀ 30 ◦C. The suspension
was stirred for 15 min, then NIS (351 mg, 1.560 mmol), TfOH (6 μL,
0.068 mmol) was added. The reaction mixture was stirred for 1 h
ꢀ 30 ◦C. The reaction mixture was gradually warmed to 0 ◦C and
quenched with Et3N. The mixture was diluted with CH2Cl2 and added
Na2S2O3, filtered through celite and concentrated in vacuo. The crude
material was quickly purified by column chromatography (Petroleum
ether–EtOAc, 5:2) to give the product 21 (745 mg, yield of 71.3%) as a
yellow syrup. For α: Rf 0.3 (2:1, petroleum ether–EtOAc); [α]D 18.5 (c
0.9, CHCl3); 1H NMR (500 MHz, CDCl3): δ 8.05–7.96 (m, 12H),
7.60–7.26 (m, 18H), 5.58 (d, J = 1.0 Hz, 1H), 5.56 (dd, J = 5.0, 1.0 Hz,
1H), 5.43 (dd, J = 6.0, 1.0 Hz, 2H), 5.40 (s, 1H), 5.39 (d, J = 4.5 Hz, 1H),
5.37 (s, 1H), 5.30 (dd, J = 5.0, 1.0 Hz, 1H), 5.26 (d, J = 2.0 Hz, 1H), 5.19
(s, 2H), 4.79–4.71 (m, 3H), 4.67 (d, J = 1.5 Hz, 2H), 4.65–4.53 (m, 4H),
4.49–4.42 (m, 2H), 4.36–4.32 (m, 2H), 4.11 (dd, J = 11.0, 4.0 Hz, 1H),
3.99 (dd, J = 11.5, 4.0 Hz, 1H), 3.90 (dd, J = 12.0, 2.5 Hz, 1H), 3.84 (dd,
J = 11.0, 3.0 Hz, 1H), 3.76 (dt, J = 9.5, 6.5 Hz, 1H), 3.51 (dt, J = 9.5, 6.5
Hz, 1H), 3.23 (t, J = 7.0 Hz, 2H), 2.65–2.62 (m, 2H), 2.50 (t, J = 6.5 Hz,
2H), 2.06 (s, 3H), 1.65–1.52 (m, 4H), 1.41–1.24 (m, 8H), 1.03 (s, 9H),
0.91 (s, 9H); 13C NMR (125 MHz, CDCl3): δ 206.0, 171.8, 165.8, 165.7,
165.5, 165.5, 165.1, 164.8, 154.0, 153.8, 133.5, 133.4, 133.3, 130.1,
130.0, 129.9, 129.9, 129.8, 129.3, 129.1, 129.0, 128.8, 128.5, 128.4,
128.4, 105.7, 105.6, 105.5, 105.5, 94.3, 94.3, 82.7, 81.9, 81.3, 81.2,
81.2, 81.0, 77.7, 77.6, 77.2, 77.2, 76.9, 76.8, 67.8, 67.6, 67.4, 65.8,
65.3, 51.4, 37.8, 29.6, 29.5, 29.3, 29.1, 28.8, 28.2, 27.9, 26.8, 26.7,
4.24. 8-Azidooctyl 2-O-levulinoyl-
α-D-arabinofuranosyl-(1 → 5)-2,3-di-
O-benzoyl- -D-arabinofuranoside (19)
α
To a solution of 18 (1.350 g, 1.53 mmol) in THF (12 mL) was added
◦
TBAF (3.0 mL, 1.0 M in THF, mmol) at 0 C under N2. The reaction
mixture was gradually warmed to rt and stirred 1h. The mixture was
concentrated in vacuo and extracted with CH2Cl2 and H2O. The organic
layer was washed with 1 N aq NH4Cl, H2O and brine, dried over Na2SO4,
filtered and concentrated. The residue was purified by column chro-
matography (Petroleum ether–EtOAc, 1:3) to give the product 19 (981
mg, yield of 85.8%) as a yellow syrup. Rf 0.25 (1:3, petroleum ether-
–EtOAc); [
α
]
33.7 (c 1.6, CHCl3); 1H NMR (500 MHz, CDCl3): δ 8.07
(dd, J = 8.0,D1.5 Hz, 4H), 7.61–7.57 (m, 2H), 7.48 (td, J = 8.0, 2.5 Hz,
26.1; HRMS–ESI–TOF calcd for [M
+
NH4]+ C81H85Cl6N4O29
:
4H), 5.49 (d, J = 3.5 Hz, 1H), 5.49 (s, 1H), 5.23 (s, 1H), 5.21 (s, 1H),
1787.3431. Found: 1787.3417.
11

X.-Y. Liang et al.
Carbohydrate Research 500 (2021) 108237
4.27. 8-Azidooctyl 3,5-di-O-[5-O-(2,2,2-trichloroethoxy)-carbonyl-2,3-
4.29. 8-Azidooctyl 3,5-di-O-[5-O-(2,2,2-trichloroethoxy)carbonyl-2,3-
di-O-benzoyl-
O-benzoyl-
α
-D-arabinofuranosyl]-
α
-D-arabinofuranosyl-(1 → 5)-2,3-di-
di-O-benzoyl-
2-deoxy-
benzoyl-
α-D-arabinofuranosyl]-2-O-(4,6-di-O-benzylidenyl-2-azido-
α
-D-arabinofuranoside (22)
α
-D-galactopyranosyl)-
α-D-arabinofuranosyl-(1 → 5)-2,3-di-O-
α
-D-arabinofuranoside (24)
To a solution of 21 (670 mg, 0.379 mmol) in CH2Cl2 (4.0 mL) and
MeOH (0.4 mL) was added NH2NH2.AcOH (45 mg, 0.492 mmol). The
reaction mixture was stirred at rt for 2 h. The resulting mixture was
added H2O and extracted with CH2Cl2. The organic layer was washed
with 0.5 N HCl, saturated aqueous NaHCO3 and brine, dried over
Na2SO4, filtered and concentrated in vacuo. The residue was purified by
column chromatography (5:2, petroleum ether–EtOAc) to afford com-
To a solution of 23 (680 mg, 0.311 mmol) in THF (8.0 mL) and
Pyridine (8.0 mL) was added HF.Pyridine (1.6 mL, 70% HF) at 0 ◦C
under N2(g). The reaction mixture was gradually warmed to rt and
stirred 12h. The mixture was concentrated in vacuo and extracted with
CH2Cl2. The organic layer was washed with 1 N aq HCl, saturated
aqueous NaHCO3 and brine, dried over Na2SO4, filtered and concen-
trated. The residue was purified by column chromatography (Petroleum
ether–EtOAc, 2:1) to give the product 24 (502 mg, yield of 82.9%) as a
pound 22 as a yellow syrup (533 mg, 84.3%). Rf 0.3 (2:1, petroleum
1
ether–EtOAc); [
α
]
D
19.9 (c 0.9, CHCl3); H NMR (500 MHz, CDCl3): δ
8.08–7.90 (m, 12H), 7.63–7.26 (m, 18H), 5.59 (dd, J = 5.0, 1.0 Hz, 1H),
5.54 (d, J = 1.0 Hz, 1H), 5.43 (d, J = 4.5 Hz, 1H), 5.41 (d, J = 1.0 Hz,
1H), 5.40 (s, 1H), 5.38 (d, J = 1.5 Hz, 1H), 5.34 (dd, J = 5.0, 1.0 Hz, 1H),
5.22 (s, 1H), 5.16 (s, 1H), 5.13 (d, J = 1.5 Hz, 1H), 4.79–4.71 (m, 5H),
4.66 (dd, J = 11.5, 5.0 Hz, 1H), 4.65 (dd, J = 11.5, 3.5 Hz, 1H),
4.57–4.48 (m, 3H), 4.38–4.31 (m, 4H), 4.11 (dd, J = 11.0, 4.5 Hz, 1H),
3.99 (dd, J = 11.5, 2.5 Hz, 1H), 3.86 (dd, J = 11.5, 1.5 Hz, 1H), 3.84 (dd,
J = 11.0, 4.0 Hz, 1H), 3.77 (dt, J = 9.5, 6.5 Hz, 1H), 3.52 (dt, J = 9.5, 6.5
Hz, 1H), 3.23 (t, J = 7.0 Hz, 2H), 3.19 (d, J = 7.5 Hz, 1H), 1.67–1.53 (m,
4H), 1.41–1.25 (m, 8H); 13C NMR (125 MHz, CDCl3): δ 165.9, 165.7,
165.6, 165.5, 165.4, 165.3, 154.0, 153.9, 133.7, 133.5, 133.5, 133.4,
130.0, 129.8, 129.8, 129.3, 129.2, 128.9, 128.8, 128.6, 128.5, 128.4,
108.1, 106.1, 105.8, 105.5, 94.3, 82.8, 82.0, 81.9, 81.6, 81.4, 81.1, 81.0,
80.9, 77.5, 76.9, 67.8, 67.5, 67.4, 66.5, 64.9, 51.4, 29.4, 29.3, 29.1,
yellow syrup. Rf 0.25 (1:1, petroleum ether–EtOAc); [
α
]
D
44.1 (c 1.8,
1
CHCl3); H NMR (500 MHz, CDCl3): δ 8.08–7.94 (m, 12H), 7.62–7.34
(m, 23H), 5.57 (d, J = 1.0 Hz, 1H), 5.52 (s, 1H), 5.52 (dd, J = 6.0, 0.5 Hz,
1H), 5.50 (s, 1H), 5.49 (d, J = 1.5 Hz, 1H), 5.42 (d, J = 6.0 Hz, 2H), 5.41
(dd, J = 6.0, 1.0 Hz, 1H), 5.33 (s, 1H), 5.26 (s, 1H), 5.23 (d, J = 2.0 Hz,
1H), 5.18 (d, J = 3.5 Hz, 1H), 4.81–4.65 (m, 6H), 4.65 (dd, J = 11.5, 5.0
Hz, 2H), 4.60–4.56 (m, 2H), 4.52–4.50 (m, 1H), 4.43 (dd, J = 7.0, 3.5
Hz, 2H), 4.39 (dd, J = 4.0, 1.5 Hz, 1H), 4.38 (dd, J = 8.5, 5.0 Hz, 1H),
4.33–4.31 (m, 1H), 4.27 (dd, J = 12.0, 1.0 Hz, 1H), 4.09 (dd, J = 11.5,
5.0 Hz, 1H), 4.07 (dd, J = 10.5, 3.5 Hz, 1H), 4.03–4.00 (m, 1H), 4.00
(dd, J = 12.0, 4.0 Hz, 1H), 3.87–3.82 (m, 3H), 3.79 (dt, J = 9.5, 6.5 Hz,
1H), 3.56 (dd, J = 10.5, 3.5 Hz, 2H), 3.53 (dt, J = 9.5, 6.5 Hz, 1H), 2.40
(d, J = 10.5 Hz, 1H), 1.67–1.53 (m, 4H), 1.44–1.26 (m, 8H); 13C NMR
(125 MHz, CDCl3): δ 165.9, 165.7, 165.6, 165.4, 165.3, 165.2, 154.0,
153.8, 137.4, 133.6, 133.4, 130.0, 129.9, 129.9, 129.8, 129.7, 129.3,
129.2, 129.0, 128.9, 128.8, 128.6, 128.5, 128.4, 128.3, 126.2, 106.1,
105.8, 105.6, 105.5, 101.2, 98.7, 94.3, 94.3, 88.4, 82.1, 81.6, 81.3, 81.1,
80.7, 79.5, 77.6, 77.5, 77.4, 77.2, 77.0, 76.9, 76.9, 75.3, 69.2, 67.8,
67.7, 67.5, 67.5, 66.8, 65.6, 63.4, 61.0, 51.4, 29.5, 29.3, 29.1, 28.8,
28.8, 26.7, 26.1; HRMS–ESI–TOF calcd for [M
+
NH4]+
C76H79Cl6N4O27: 1689.3063. Found: 1689.3070.
4.28. 8-Azidooctyl 3,5-di-O-[5-O-(2,2,2-trichloroethoxy)carbonyl-2,3-
di-O-benzoyl- -D-arabinofuranosyl]-2-O-(4,6-di-O-benzylidenyl-3-O-tert-
butyldiphenylsilyl-2-azido-2-deoxy- -D-galactopyranosyl)- -D-
arabinofuranosyl-(1 → 5)-2,3-di-O-benzoyl- -D-arabinofuranoside (23)
α
26.7, 26.1; HRMS–ESI–TOF calcd for [M + NH4]+ C89H88Cl6N6NaO31
:
α
α
1964.3969. Found: 1964.3962.
α
4.30. 8-Azidooctyl 3,5-di-O-[
benzylidenyl-2-azido-2-deoxy-
arabinofuranosyl-(1 → 5)- -D-arabinofuranoside (25)
α
-D-arabinofuranosyl]-2-O-(4,6-di-O-
A mixture of thioglycoside 5 (443 mg, 0.695 mmol) and acceptor 22
(775 mg, 0.464 mmol), and freshly activated 4 Å molecular sieves
(1.150 g) in dry CH2Cl2 (13 mL) was cooled to ꢀ 30 ◦C. The suspension
α
-D-galactopyranosyl)- -D-
α
α
was stirred for 15 min, then NIS (196 mg, 0.867 mmol), TfOH (3 μL,
To a solution of 24 (470 mg, 0.242 mmol) in MeOH (12.0 mL) was
added CH3ONa (47 mg). The reaction mixture was stirred 12h, then
concentrated in vacuo. The residue was purified by column chroma-
tography (CH2Cl2–MeOH, 1:3) to give the product 25 (209 mg, yield of
0.035 mmol) was added. The reaction mixture was stirred for 1 h
ꢀ 30 ◦C. The reaction mixture was gradually warmed to 0 ◦C and
quenched with Et3N. The mixture was diluted with CH2Cl2 and added
Na2S2O3, filtered through celite and concentrated in vacuo. The crude
material was quickly purified by column chromatography (Petroleum
ether–EtOAc, 4:1) to give the product 23 (816 mg, yield of 80.5%) as a
88.8%) as a white syrup. Rf 0.2 (1:3, CH2Cl2–MeOH); [
α]D 160.8 (c 1.9,
1
MeOH); H NMR (500 MHz, CD3OD): δ 7.56–7.53 (m, 2H), 7.39–7.34
(m, 3H), 5.64 (s, 1H), 5.24 (d, J = 3.5 Hz, 1H), 5.20 (d, J = 1.0 Hz, 1H),
5.11 (d, J = 1.5 Hz, 1H), 4.99 (d, J = 1.5 Hz, 1H), 4.32 (d, J = 3.0 Hz,
1H), 4.30 (dd, J = 2.5, 1.5 Hz, 1H), 4.26–4.20 (m, 3H), 4.16 (dd, J =
12.5, 1.5 Hz, 1H), 4.15 (dd, J = 10.5, 3.5 Hz, 1H), 4.05–3.94 (m, 8H),
3.87–3.83 (m, 4H), 3.80–3.69 (m, 6H), 3.68 (dd, J = 12.0, 5.0 Hz, 2H),
3.47 (dt, J = 9.5, 6.5 Hz, 1H), 3.29 (t, J = 7.0 Hz, 2H), 1.63–1.56 (m,
4H), 1.39–1.30 (m, 8H); 13C NMR (125 MHz, CD3OD): δ 139.7, 129.9,
129.1, 127.6, 109.5, 109.5, 109.1, 107.3, 102.3, 99.6, 87.5, 85.7, 85.6,
83.8, 83.6, 83.4, 83.4, 82.6, 82.3, 78.9, 78.8, 78.6, 77.6, 70.3, 69.0,
68.2, 67.7, 67.3, 65.2, 63.1, 63.0, 61.5, 52.5, 30.7, 30.4, 30.2, 29.9,
yellow syrup. For α: Rf 0.35 (5:2, petroleum ether–EtOAc); [α]D 30.2 (c
1.0, CHCl3); 1H NMR (500 MHz, CDCl3): δ 8.06–7.91 (m, 12H),
7.71–7.67 (m, 4H), 7.58–7.30 (m, 27H), 7.25 (t, J = 8.0 Hz, 2H), 5.50 (s,
1H), 5.47–5.45 (m, 3H), 5.41 (t, J = 4.5 Hz, 2H), 5.37 (d, J = 1.0 Hz,
1H), 5.31 (s, 1H), 5.20 (s, 1H), 5.18 (d, J = 3.5 Hz, 1H), 5.05 (d, J = 1.5
Hz, 1H), 4.98 (s, 1H), 4.79–4.65 (m, 6H), 4.62 (td, J = 12.0, 5.0 Hz, 2H),
4.54–4.50 (m, 2H), 4.34–4.22 (m, 5H), 4.04 (dd, J = 10.5, 4.0 Hz, 2H),
3.91 (dd, J = 11.5, 5.0 Hz, 1H), 3.86 (dd, J = 7.5, 3.0 Hz, 1H), 3.84 (dd,
J = 8.5, 3.0 Hz, 1H), 3.74 (dd, J = 8.5, 3.0 Hz, 1H), 3.72 (dd, J = 10.0,
6.5 Hz, 1H), 3.62 (d, J = 11.0 Hz, 2H), 3.49–3.43 (m, 3H), 3.22 (t, J =
7.0 Hz, 2H), 1.64–1.52 (m, 4H), 1.40–1.22 (m, 8H), 1.01 (s, 9H); 13C
NMR (125 MHz, CDCl3): δ 165.8, 165.7, 165.5, 165.4, 165.1, 165.1,
154.0, 153.9, 137.8, 135.8, 134.3, 133.5, 133.3, 132.8, 130.0, 129.9,
129.9, 129.8, 129.3, 129.2, 129.1, 129.0, 128.9, 128.8, 128.5, 128.5,
128.4, 128.1, 127.8, 127.5, 126.1, 105.7 (JH1-C1 = 179.1), 105.7 (JH1-C1
= 179.5), 105.6 (JH1-C1 = 175.6), 105.5 (JH1-C1 = 174.7), 100.3, 99.0
(JH1-C1 = 172.5), 94.4, 94.3, 88.1, 82.0, 81.9, 81.6, 81.4, 81.2, 81.1,
80.8, 79.2, 77.5, 77.4, 77.4, 77.2, 77.0, 76.9, 75.2, 69.7, 69.0, 67.8,
67.6, 67.4, 66.6, 66.0, 63.4, 61.1, 60.4, 51.4, 29.5, 29.3, 29.1, 28.8,
26.8, 26.7, 26.1, 21.1, 19.3, 14.2; HRMS–ESI–TOF calcd for [M+Na]+
C105H106Cl6N6NaO31Si: 2207.4695. Found: 2207.4686.
27.8, 27.2, 26.1; HRMS–ESI–TOF calcd for [M+Na]+ C41H62N6NaO21
:
997.3860. Found: 997.3861.
4.31. 8-Aminooctyl 3,5-di-O-[
deoxy- -D-galactopyranosyl)- -D-arabinofuranosyl-(1 → 5)-
arabinofuranoside (26)
α-D-arabinofuranosyl]-2-O-(2-amino-2-
α
α
α
-D-
To a stirred solution of 25 (35 mg, 0.036 mmol) in THF–H2O (2.1 mL,
v:v = 1:1) was added 20% Pd(OH)2/C (8 mg). After stirring overnight
under an H2 atmosphere, the reaction mixture was filtered through
Celite and the filtrate was concentrated to give the product 26 (22 mg,
12

X.-Y. Liang et al.
Carbohydrate Research 500 (2021) 108237
[2] (a) D.K. Baeschlin, A.R. Chaperon, S.V. Ley, Chem. Eur J. 6 (2000) 172–186;
(b) Y. Zhang, J. Jimenez-Barbero, J.D.C. Codee, Angew. Chem. Int. Ed. 41 (2002)
390–412;
yield of 73.4%) as
a yellow syrup. Rf 0.15 (3:3:3:4 EtOAc–-
CH3OH–AcOH–H2O); [
α
]D 105.5 (c 0.5, H2O); 1H NMR (700 MHz, D2O):
δ 5.37 (s, 1H), 5.18 (s, 1H), 5.12 (s, 2H), 5.03 (s, 1H), 4.37–4.34 (m, 1H),
4.32 (s, 1H), 4.27 (d, J = 3.5 Hz, 1H), 4.19–3.71 (m, 30H), 3.62 (dt, J =
7.0, 3.5 Hz, 1H), 3.38 (t, J = 2.1 Hz, 0.2H), 3.04–3.02 (m, 1H), 3.38 (t, J
= 2.1 Hz, 0.2H), 3.01 (d, J = 7.7 Hz, 0.2H), 1.69–1.63 (m, 3H),
1.37–1.26 (m, 10H), 0.91 ((t, J = 7.0 Hz, 3H); 13C NMR (125 MHz, D2O):
δ 108.3, 108.2, 107.7, 106.7, 97.0, 86.2, 85.1, 85.1, 82.5, 82.3, 82.2,
82.0, 81.8, 81.3, 77.6, 77.6, 77.2, 73.0, 69.6, 69.1, 68.1, 67.1, 67.0,
62.7, 62.2, 62.1, 62.0, 51.5, 49.8, 40.5, 29.5, 29.1, 29.0, 27.6, 26.4,
26.0, 24.2, 21.5, 14.2; HRMS–ESI–TOF calcd for [M+Na]+
C34H62N2NaO21: 857.3740. Found 857.3737.
(c) A.V. Demchenko, Curr. Org. Chem. 7 (2003) 35–49;
(d) A.V. Demchenko, Synlett 9 (2003) 1225–1240;
(e) J.L. Stockdill, H.M. Nguyen, Chem. Sci. 10 (2019) 10475–10480.
[3] (a) H. Paulsen, C. Kolar, W. Stenzel, Chem. Ber. 111 (1978) 2358–2369;
(b) R.U. Lemieux, R.M. Ratcliffe, Can. J. Chem. 57 (1979) 1244–1251;
¨
¨
(c) T.S. Karkkainen, K.P. Kartha, D. MacMillan, R.A. Field, Carbohydr. Res. 343
(2008) 1830–1834;
(d) J. Park, S. kawatkar, J.H. Kim, G.J. Boons, Org. Lett. 9 (2007) 1959–1962;
(e) V.L. Campo, I. Carvalho, S. Allman, B.G. Davis, R.A. Field, Org. Biomol. Chem.
5 (2007) 2645–2657.
[4] (a) K. Benakli, C. Zha, R.J. Kerns, J. Am. Chem. Soc. 123 (2001) 9461–9462;
(b) P. Wei, R.J. Kers, J. Org. Chem. 70 (2005) 4195–4198;
(c) J. Kerns, C. Zha, K. Benakli, Y.Z. Liang, Tetrahedron Lett. 44 (2003)
8069–8072;
(d) S. Manabe, K. Ishii, Y. Ito, J. Am. Chem. Soc. 128 (2006) 10666–10667;
(e) Y. Geng, L.H. Zhang, X.S. Ye, Chem. Commun. (2008) 597–599;
(f) Y. Geng, L.H. Zhang, X.S. Ye, Tetrahedron 64 (2008) 4949–4958.
[5] J.E. Yule, T.C. Wong, S.S. Ganghi, D.X. Qiu, M.A. Riopel, R.R. Koganty,
Tetrahedron Lett. 36 (1995) 6839–6842.
Declaration of competing interest
The authors declare that they have no known competing financial
interests or personal relationships that could have appeared to influence
the work reported in this paper.
[6] (a) A. Imamura, H. Ando, H. Ishida, M. Kiso, Tetrahedron Lett. 44 (2003)
6725–6728;
(b) A. Imamura, H. Ando, H. Ishida, M. Kiso, Org. Lett. 7 (2005) 4415–4418;
(c) A. Imamura, N. Matsuzawa, H. Ishida, M. Kiso, J. Org. Chem. 81 (2016)
9086–9104;
Acknowledgments
(d) Y.Z. Zhang, J.D.C. Codee, Angew. Chem. Int. Ed. 59 (2020) 12746–12750.
[7] D.M. Yang, Y. Chen, X.Y. Liang, Org. Lett. 20 (2018) 2287–2290.
[8] (a) G.J. Boons, Contemp. Org. Synth. 3 (1996) 173–200;
(b) S.V.D. Vorm, J.D.C. Codee, J. Org. Chem. 82 (2017) 4793–4811.
[9] A.B. Ingle, W.C. Hung, T.K.K. Mong, Org. Lett. 15 (2013) 5290–5293.
Thanks to the University of Alberta for providing sample analysis.
Liang, X.-Y. thanks the National Natural Science Foundation of China
(NSFC-21402131) and Zigong science and Technology Bureau project
(LYJ4204), and Liang X.-Y. and Fan, H.-J. thank the Science Foundation
of Sichuan University of Science & Engineering (2020RC02, 2020RC06).
´
´
[10] A. Liptak, J. Imre, A. Neszmelyi, Tetrahedron 38 (1982) 3721–3727.
[11] D. Crich, S.X. Sun, J. Am. Chem. Soc. 119 (1997) 11217–11223.
[12] L. Zhang, K. Shen, T.L. Lowary, J. Org. Chem. 83 (2018) 7659–7671.
[13] Alcohols 6d, 6e and 6h are commercially available. 6g: see supporting documents
for synthesis method; All others were prepared by reported methods. For 6c: X. Y.
Liang, J. S. Yang, Tetrahedron., 2010, 66, 87-93. 6f: D. Falguni, A. Laurens,
Carbohydr. Res., 1990, 202, 239-255. 6i: X. Y. Liang, J. S. Yang, Org. Lett., 2013,
15, 2834-2837. 6j: G. J. Capozzi, Org. Chem 66 (2001) 8787–8792.
[14] (a) X. Wang Wang, A.A. Ribeiro, Z. Guan, S.C. McGrath, R.J. Cotter, C.R.H. Raetz,
Biochemistry 45 (2006) 14427–14440;
Appendix A. Supplementary data
Supplementary data to this article can be found online at https://doi.
org/10.1016/j.carres.2021.108237.
(b) W.J. Peng, L. Zou, S. Bhamidi, T.L. Lowary, J. Org. Chem. 77 (2012)
9826–9832.
References
[15] M. Joe, Y. Bai, R.C. Nacario, T.L. Lowary, J. Am. Chem. Soc. 129 (2007)
9885–9901.
[1] (a) R.A. Dwek, Chem. Rev. 96 (1996) 683–720;
[16] See experiment procedure for synthesis method and data of compound 20.
[17] (a) K. Boke, I. Lundt, C. Pedersen, Tetrahedron Lett. 13 (1973) 1037–1043;
(b) P.K. Agrawal, Phytochemistry 31 (1992) 3307–3330;
(b) B.G. Davis, Chem. Rev. 102 (2002) 579–602;
(c) I. Capila, R.J. Linhardt, Angew. Chem. Int. Ed. 41 (2002) 390–412;
(d) T.J. Boltje, T. Buskas, G.J. Boons, Nat. Chem. 1 (2009) 611–622;
(e) N.C. Bamford, D.C. Sheppard, P.L. Howell, Nat. Commun. 11 (2020) 2450.
(c) R.A.E. Edden, J. Keeler, J Magn Reson. 166 (2004) 53–68.
13