Efficient synthesis of a 6-deoxy-talose containing tetrasccharide found in Franconibacter helveticus LMG23732T

Article abstract of DOI:10.1016/j.carres.2018.01.002

Synthesis of the 6-deoxy-talose (6-dTal) containing tetrasaccharide, naturally found in Franconibacter helveticus LMG23732T, has been described. The synthetic method utilized an allyloxyethylidene group for protecting the 1-OH and 2-OH groups of rhamnopyranose and a redox reaction for synthesizing 6-deoxy talose, which eventually formed a disaccharide containing α-Glcp-(1→2)-6dTalp configured glycosidic bonds using a [2 + 2] synthetic strategy.

Full text of DOI:10.1016/j.carres.2018.01.002

Accepted Manuscript
Efficient synthesis of a 6-deoxy-talose containing tetrasccharide found in
T
Franconibacter helveticus LMG23732
Yiren Xu, Tianheng Xu, Jianjun Zhang
PII:
S0008-6215(17)30909-6
10.1016/j.carres.2018.01.002
CAR 7506
DOI:
Reference:
To appear in: Carbohydrate Research
Received Date: 12 December 2017
Revised Date: 11 January 2018
Accepted Date: 11 January 2018
Please cite this article as: Y. Xu, T. Xu, J. Zhang, Efficient synthesis of a 6-deoxy-talose containing
T
tetrasccharide found in Franconibacter helveticus LMG23732 , Carbohydrate Research (2018), doi:
10.1016/j.carres.2018.01.002.
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ACCEPTED MANUSCRIPT
Efficient synthesis of a 6-deoxy-talose containing tetrasccharide
found in Franconibacter helveticus LMG23732T

ACCEPTED MANUSCRIPT
Efficient synthesis of a 6-deoxy-talose containing tetrasccharide
found in Franconibacter helveticus LMG23732T
Yiren Xu, Tianheng Xu, Jianjun Zhang *
Department of Applied Chemistry, China Agricultural University, Beijing 100193, PR China.
Author. E-mail: ryandota@sina.com (Y.X.); 1310060111@cau.edu.cn (T.X.)
*Corresponding author. Tel/Fax: 86 10 62732219; E-mail: zhangjianjun@cau.edu.cn (J.Z.);

ACCEPTED MANUSCRIPT
Abstract
Synthesis of the 6-deoxy-talose (6-dTal) containing tetrasaccharide, naturally found in
Franconibacter helveticus LMG23732T, has been described. The synthetic method utilized an
allyloxyethylidene group for protecting the 1-OH and 2-OH groups of rhamnopyranose and a
redox reaction for synthesizing 6-deoxy talose, which eventually formed a disaccharide containing
α-Glcp-(1→2)-6dTalp configured glycosidic bonds using a [2+2] synthetic strategy.
Keywords: Franconibacter helveticus; Lipopolysaccharides; O-specific polysaccharide;
Tetrasaccharide; Synthesis
1. Introduction
Lipopolysaccharides (LPSs) are the structural components of the outer cell membranes of
Gram-negative bacteria. The chemical structure of LPS is comprised of three distinct domains:
lipid A, a core oligosaccharide, and the O-polysaccharide (O-PS) [1-4]. Among these domains, the
O-PS, which is exposed to the external environment, is significantly involved in host-pathogen
cross-talk[5-7]. The inner structure of the O-PS typically consisted of multiple repeating units of
1-4 monosaccharide residues. The antigenic nature of these glycans renders them suitable as
targets for vaccine development [8-11]. Recent reports showed that the repeating units of the
O-chain polysaccharide (OPS) of the lipopolysaccharides of Franconibacter LMG23732T possess
an unusual structural feature that consists of three 6-deoxy sugars [6-deoxy-talose (6-dTal)] in the
main chain and one D-Glcp as the terminal branch [12] (scheme 1):
OAll
O
O
O
HO
HO
HO
HO
O
O
O
O
HO
HO
HO
HO
O
O
O
O
O
HO
HO
HO
O
O
HO
O
OH
OH
OH
HO
OH
OH
OH
n
O
1
2
Scheme 1. The repeating unit of LPSs from the bacterium Franconibacter helveticus LMG23732T (1) and the
synthesized oligosaccharide (2).
6-Deoxy-L-talose is present in many biologically important glycopeptidolipids (GPLs)[13-17]
and antigenic bacterial lipopolysaccharides (LPSs) [18-23], where the O-2 or O-3 is glycosylated
by other sugar units. The active involvement of these carbohydrates in bacterial physiology and
pathogenesis inspired many scientists to synthesize LPS oligosaccharides and study their
structure-bioactivity relationships. The present investigation was aimed at synthesizing a
well-defined tetrasaccharide repeating unit (scheme 1) of LPSs present in the outer cell membrane
of the bacterium Franconibacter helveticus LMG23732T.

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2. Results and discussion
Scheme 2. The retrosynthesis strategy for synthesizing target tetrasccharide (2)
The synthesis strategy of tetrasccharide 2 is outlined in Scheme 2. Since Fraser-Reid and
co-workers observed that O-allyl substitution could be selectively deprotected by
N-bromosuccinimide[24], the amount of glycoside synthesis were involved in allyl group as a
protection strategy[25-28]. The allyl glycoside was stable and easily prepared [29-32]; moreover,
it could be selectively oxidized to O-formylmethyl glycoside, which was an important
intermediate in the synthesis of many activite molecules [33-35]. Therefore, we selected the allyl
moiety as the anomeric protected group and the allyl glycoside as the end of the target
oligosaccharide in this study, which might also be used in future investigations on this
tetrasaccharide. The retrosynthetic analysis indicates that tetrasccharide 2 can be prepared through
a convergent strategy involving [2+2] glycosylation of two disaccharides: the disaccharide donor 3
and the disaccharide acceptor 4. These two disaccharides 3 and 4 can be synthesized from
glucose- or talose-derived building blocks (5, 6, 7 and 8). The compound 8 can be transformed to
6 or 7 by suitable modifications, and utilized for synthesizing the disaccharides 3 and 4.

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Scheme 3. The synthesis of glucose- or talose-derived monosaccharide building blocks
L
-talosyl acceptor 6 and
following the synthetic strategy as described in the scheme 3. The intermediate 3 was synthesized
following seven steps from the commercially available -rhamnose[36]. The compound 9 was
L-talosyl donor 7 were prepared from the same intermediate 9
L
treated with allyl alcohol in the presence of 2,4-lutidine and tetrabutylammonium bromide (TBAB)
to obtain 10. The crude product was deacetylated using MeOH-NH3, and the reaction mixture was
concentrated and co-evaporated with toluene to obtain 11. The C-3 hydroxyl group of 11 was
selectively acylated with benzoyl chloride in dichloromethane at
pyridine and catalytic amounts of 4-dimethylaminopyridine(DMAP) to obtain
3-O-benzoyl-1,2-O-allyloxyethylidene-β- -talopyranose (12) (yield: 72%). The regioselectivity
−
25o C, in the presence of
L
was not surprising since the equatorially oriented 3-OH is more reactive than the axial 2-OH or
4-OH. Similar regioselective protection was observed for rhamno- and taloside derivatives.[17, 20]
The equatorial 4-OH of the compound 12 was oxidized to ketone using dimethyl sulfoxide
(DMSO), triethylamine, and phenylphosphonic dichloride, and the ketone was subsequently
reduced to axial 4-OH by treating with NaBH4 in the presence of MeOH (one-pot-reaction
method)[17] to obtain compound 13 (yield: 54%). These structural modifications were confirmed
by the 1H NMR spectrum: the H-3 coupling constants of compound 12 (dd, J 4.1 Hz and 9.6 Hz at
δ 5.16
confirming the correct relative configuration. Benzoylation of the 4-OH of compound 13 yielded
the 3,4-di-O-benzoyl-1,2-O-allyloxyethylidene-β- -talopyranoside 14. A previous study of
orthoester rearrangement reaction showed that 1,2-O-allyloxyethylidene-β- -rhamnopyranose can
be intermolecularly rearranged to produce a disaccharide with α- -Rhap-(1→2)- -Rhap
−5.21) were compared to that of the compound 13 (t, J 2.5 Hz at δ 5.63−5.64) for
L
L
L
L
configured glycosidic bonds when treated with trimethylsilyl trifluoromethanesulfonate (TMSOTf)
in anhydrous CH2Cl2 (Shown in Figure 1)[37, 38].

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Figure 1. Possible mechanism of TMSOTfpromoted transformation of rhamnosyl orthoester[38]
In this study, we hope to replicate a similar reaction with orthoester 14 and expected to obtain
taloside disaccharide 22 (scheme 3 and scheme 4); however, the objective was not achieved as we
received monosaccharide 8 as the main reaction product. The possible mechanism is shown in
Figure 2. There were two paths for the TMSOTf-catalyzed transformation of talopranosyl
orthoester; path 1 was the normal rearrangement generating the corresponding monosaccharide,
which yielded the same result as rhamnosyl orthoester. In path 2, the larger steric effect of the
axial 4-OBz in talosyl orthoester compared to equatorial 4-OBz in rhamnosyl orthoester hindered
the reaction between the axial 2-OTMS and the anomeric carbon of intermediate, because of
which, the talosyl orthoester rearrangement could not form the disaccharide.
Figure 2. Possible mechanism of TMSOTf-promoted transformation of talosyl orthoester
Using compound 8, the 2-OH L-talosyl acceptor 6 was obtained conveniently in a solution
containing AcCl-methanol (1: 50 v/v) [39] ; in addition, the PdCl2-catalyzed removal of the allyl
group in compound 8, followed by anomeric trichloroacetimidation, yielded 72% donor 7 in
two-steps[40]. The glucosyl donor 5 was synthesized via a two-stepped reaction from the reported
product 16[41]. The anomeric acetate was selectively removed by treating with ethylene diamine:
AcOH (1: 1) in THF to obtain 17 with 77% yield. Trichloroacetimidation of 17 with CCl3CN in
the presence of 1,5-diazabicyclo(5,4,0)undec-5-ene (DBU) produced the trichloroacetimidate 5
with satisfactory yield.

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Scheme 4. The synthesis of disaccharide building blocks
The disaccharide acceptor 4 and disaccharide donor 3 were synthesized conveniently using
monosaccharide building blocks 5, 6 and 7 (Scheme 4). The compound 5 was glycosylated with
the compound 6 in TMSOTf to obtain the corresponding α-(1→2)-linked disaccharide 18 with 74%
1
yield. The 1,2-cis configuration was confirmed by analyzing the H NMR signal of H-1-Glcp at
4.94 ppm (d, 1H, J 3.6 Hz). The allyl group in 18 was cleaved with palladium chloride (PdCl2),
debenzylated with Pd/C under H2 in MeOH, and then acetylated with acetic anhydride in pyridine
to produce the compound 20 with 79% yield. The disaccharide donor 3 was synthesized from 20
with 73% yield using a two-stepped reaction involving selective de-1-O-aetylation, followed by
trichloroacetimidate formation. The acetyl (Ac) group at the C-2 in
L-talosyl donor 7 activated the
α-(1→2)-linkage to glycosylate -talosyl acceptor 6 and finally produce disaccharide 22 with 75%
L
yield. Further, treating 22 with acetyl chloride in MeOH/CH2Cl2 (1: 1 v/v) at 0°C[42] to remove
the acetyl group produced disaccharide acceptor 4 with 83% yield.
Scheme 5. The synthesis of target tetrasccharide 2
Finally, tetrasccharide 2 was synthesized following Scheme 5. The disaccharide acceptor 4
and the disaccharide donor 3 underwent Schmidt glycosylation to produce the completely
protected tetrasccharide 23, and the success of the reaction was confirmed by 1H NMR signals at δ
5.24 (H1-Talp1), 5.13 (H1-Talp2), 4.75 (H1-Talp3), and 4.68 (H1-Glcp), and 13C NMR signals at δ
97.2 (C1-Talp3), 97.5 (C1-Talp2), 100.4 (C1-Talp1), and 100.7 (C1-Glcp), which indicated the
presence of four anomeric carbons. Complete removal of the protecting groups in 23 was achieved
by hydrolyzing the compound with saturated NH3–MeOH to obtain the desired tetrasaccharide 2

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with 70% yield. The structures were confirmed by the 1H NMR signals at δ 5.06 (H1-Tlap1), 5.06
(H1-Talp2), 4.94 (H1-Glcp), and 4.87 (H1-Talp3) which were the characteristic peaks of anomeric
protons. The signals at δ 5.93−5.81 (m, 1H, OCH2CHCH2) and 5.31−5.22 (m, 2H, OCH2CHCH2)
were the characteristic peaks of the allyl group; In 13C NMR, the signals at δ 100.7 (C1-Talp1),
100.4 (C1-Talp2), 97.5 (C1-Glcp), and 97.2 (C1-Talp3) were the characteristic peaks of anomeric
carbons, and the signals at δ 132.9 (OCH2CHCH2) and 118.6 (OCH2CHCH2) were the
characteristic peaks of the allyl group, as was evident from the 13C-1H HSQC spectrum. Although
1
one of the characteristic peaks of the allyl group was sheltered by other peaks in H NMR with
signals at δ 3.8−4.2, the high resolution mass spectrometry report yielded the precise molecular
mass of 2 (676.3035), which was indicative of anomeric integrity.
3. Conclusion
In summary, we reported a convergent total synthesis of a tetrasccharide analogue 2, which is
related to the repeating unit of O-specific polysaccharide present in the outer cell membrane of
Franconibacter helveticus LMG23732T. This efficient synthesis features the preparation of a key
monosaccharide intermediate, L-taloside 8 from 1,2-O-allyloxyethylidene-L-rhamnose derivative
via orthoester rearrangement, and the monosaccharide can be easily converted to the
monosaccharide donor 7 or acceptor 6. The 1,2-cis glycosidic bonds, α-Glcp-(1-2)-6dTalp of the
disaccharide 18 was formed by glycosylating the monosaccharide donor 5 with monosaccharide
acceptor 6 at low temperature. The three-stepped reaction from 18 to 20 was followed by a
two-stepped reaction to finally generate the disaccharide donor 3 with good yield. This study will
enrich the O-specific polysaccharide library and contribute towards future studies in the area of
carbohydrate chemistry.
4. Experimental
4.1 Materials and methods
1H and 13C NMR spectra were recorded using the Bruker AVANCE600 spectrometers (1H
NMR-300 MHz; 13C NMR-75 MHz) with CDCl3 or D2O as solvents. TMS (δ 0.000 ppm for 1H)
and CDCl3 (δ 77.00 ppm for 13C) were the internal references. The 1H NMR data are reported as
follows: chemical shift, integration, multiplicity (app = apparent, parobsc = partially obscure,
ovrlp = overlapping, s = singlet, d = doublet, dd = doublet of doublet, t = triplet, q = quartet, m=
multiplet) and coupling constants in Hertz. All 13C NMR spectra were recorded with complete
proton decoupling. The high-resolution mass spectra (HRMS) were recorded using the Bruker
Daltonics Bio-TOF-Q III (ESIMS) spectrometer. Thin layer chromatography (TLC) was
performed on silica gel HF254 plates, and detected by an UV detector or by charring with 15%
(v/v) H2SO4 in methanol. All commercially available reagents were purchased from Sinopharm,
Shanghai, China, and used without further purification. All reactions were monitored by TLC.
Column chromatography was conducted using a silica gel plug (200-300 mesh), and a mixture of
ethyl acetate (EtOAc), and petroleum ether (bp 60-90 °C) was used as the eluent.

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4.2. 3-O-benzoyl-1,2-O-allyloxyethylidene-β-L-rhamnopyranoside (12)
A solution of 11 (5.00 g, 20.35 mmol) in CH2Cl2 (250 mL) was mixed with pyridine (20 ml)
and DMAP (0.05 g, 0.41 mmol) at −25°C in a N2 environment. The reaction mixture was stirred
for 30 min, and BzCl (2.34 ml, 20.32 mmol) in CH2Cl2 (50 ml) was added dropwise. The resultant
mixture was stirred for another 3 h, and the completion of the reaction was confirmed by TLC
(petroleum ether/ethyl acetate 1:1) analysis. The reaction was then quenched with chilled H2O
(300 mL), and extracted with CH2Cl2 (3 × 150 mL). The organic phases were combined, dried
over Na2SO4, and concentrated. The residue was purified by flash column chromatography
22
(petroleum ether/ethyl acetate 2.5:1) to yield 11 (4.93 g, 72%) as a colorless syrup. [α]D −14.5°
1
(c 1.0, CHCl3). H NMR (300 MHz, CDCl3): δ 7.61−7.36 (m, 5H, ArH), 5.92−5.79 (m, 1H,
OCH2CHCH2), 5.47 (d, 1H, J = 2.3 Hz, H-1), 5.26−5.07 (m, 2H, OCH2CHCH2), 5.21−5.16 (dd,
1H, J = 4.1 Hz, 9.6 Hz, H-3), 4.70 (dd, 1H, J = 2.3 Hz, 4.1Hz, H-2), 4.09−3.96 (m, 2H,
OCH2CHCH2), 3.82 (t, 1H, J = 9.4 Hz, H-4), 3.45−3.53 (m, 1H, H-5), 1.76 (s, 3H, CH3),
1.40−1.38 (d, 3H, J = 6.1 Hz, H-6); 13C NMR (75 MHz, CDCl3) : δ 166.4 (COPh), 133.8, 133.2,
132.9, 129.7, 128.1, 128.0, 123.7, 116.2, 97.0 (C-1), 74.1, 70.7, 69.9, 63.2, 24.8, 17.3 (C-6).
ESI-HRMS [M + NH4]+ calculated for C18H26NO7 368.1709 found 368.1704.
4.3. 3-O-benzoyl-1,2-O-allyloxyethylidene-β-L-talopyranoside (13)
A solution of 12 (4.00 g, 11.42 mmol) in CH2Cl2 (150 mL) was mixed with DMSO (3.2 ml,
40.96 mmol) and Et3N (8 ml, 78.50 mmol) at 0°C. The reaction mixture was stirred for 30 min,
and phenylphosphonic dichloride (3.44 mL, 22.83 mmol) in CH2Cl2 (25 ml) was added dropwise.
The resultant mixture was stirred for 2.5 h at room temperature, and the completion of the reaction
was confirmed by TLC (petroleum ether/ethyl acetate 4:1) analysis. Methanol (100 ml) and
NaBH4 (1.20 g, 31.72 mmol) at 0°C was added to the reaction mixture. The resultant mixture was
stirred with continuous addition of water (250 mL); the mixture was extracted with CH2Cl2 (3 ×
100 mL); the organic layer was sequentially washed with saturated aqueous NaHCO3 solution
(250 mL) and brine (2 × 200 mL), and then dried over anhydrous sodium sulfate, filtered, and
concentrated under vacuum. The residue was purified by flash column chromatography
(petroleum ether/ethyl acetate 6:1) to obtain 13 (2.10 g, 54%) as a colorless syrup. [α]D22 −25.6° (c
1
1.0, CHCl3). H NMR (300 MHz, CDCl3): δ 8.04−8.01 (m, 2H, ArH), 7.65−7.60 (m, 1H, ArH),
7.56−7.46 (m, 2H, ArH), 5.97−5.84 (m, 1H, OCH2CHCH2), 5.64−5.63 (t, 1H, J = 2.5 Hz, H-3),
5.54 (d, 1H, J = 2.3 Hz, H-1), 5.31−5.15 (m, 2H, OCH2CHCH2), 4.21 (dd, 1H, J1 = 2.0 Hz, J2 =
2.5 Hz, H-2), 4.14−4.08 (m, 2H, OCH2CHCH2), 4.01−3.97 (m, 1H, H-4), 3.57−3.52 (m, 1H, H-5),
2.46 (d, 1H, J = 12.7 Hz, OH), 1.81 (s, 3H, CH3), 1.36 (d, 3H, J = 6.5 Hz, H-6); 13C NMR (75
MHz, CDCl3) : δ 164.1 (COPh), 133.5, 133.4, 129.4, 128.3, 122.7, 96.36 (C-1), 74.1, 68.2, 67.9,
67.7, 67.6, 24.5, 16.1 (C-6). ESI-HRMS [M + NH4]+ calculated for C18H26NO7 368.1709 found
368.1704.
4.4. 3,4-di-O-benzoyl-1,2-O-allyloxyethylidene-β-L-talopyranoside (14)
A solution of 13 (2.00 g, 5.71 mmol) in CH2Cl2 (50 mL) was mixed with pyridine (10 mL) at
0°C in a nitrogenous environment. The reaction mixture was stirred for 5 min, and benzoyl
chloride (0.79 mL, 6.90 mmol) in CH2Cl2 (5 ml) was added dropwise. The resultant mixture was
stirred for another 4 h, and the completion of the reaction was confirmed by TLC (petroleum
ether/ethyl acetate 4:1) analysis. The reaction was then quenched with chilled H2O (200 mL), and
the reaction mixture was extracted with CH2Cl2 (3 × 150 mL). The organic phases were combined,

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dried over Na2SO4, and concentrated. The residue was purified by flash column chromatography
(petroleum ether/ethyl acetate 10:1) to obtain 14 (2.28 g, 88%) as a colorless syrup. [α]D22 −37.7°
(c 1.0, CHCl3). 1H NMR (300 MHz, CDCl3): δ 8.16−8.05 (m, 4H, ArH), 7.64−7.45 (m, 6H, ArH),
5.98−5.85 (m, 1H, OCH2CHCH2), 5.72 (t, 1H, J = 2.3 Hz, H-3), 5.63 (d, 1H, J = 2.6 Hz, H-1),
5.31, 5.26, 5.18, 5.14, (m, 2H, OCH2CHCH2), 5.10 (t, 1H, J = 1.2 Hz, H-4), 4.22−4.17 (m, 2H,
H-2, H-5), 4.12−4.09 (m, 2H, OCH2CHCH2), 1.90 (s, 3H, CH3), 1.35 (d, 3H, J = 6.5 Hz, H-6); 13C
NMR (75 MHz, CDCl3) : δ 165.5 (COPh), 163.9 (COPh), 133.7, 133.5, 133.1, 129.7, 129.5,
129.1, 128.7, 128.3, 128.1, 123.5, 116.5, 96.2 (C-1), 67.9, 67.4, 66.7, 63.1, 25.2, 16.4 (C-6).
ESI-HRMS [M + NH4]+ calculated for C25H30NO8 472.1971 found 472.1966.
4.5. Allyl 2-O-acetyl-3,4-di-O-benzoyl-α-L-talopyranoside (8)
A solution of 14 (2.00 g, 4.4 mmol) in anhydrous CH2Cl2 (50 ml) was mixed with 4 Å
molecular sieves (0.5 g) at 0°C under N2. The reaction mixture was stirred for 30 min, TMSOTf
(10 μL) was added and the mixture was stirred for another 2 h until TLC analysis (petroleum
ether-ethyl acetate 5:1) showed that the reaction was complete. The reaction was quenched with
Et3N (0.6 ml) at 0°C and the reaction mixture was diluted with CH2Cl2. Molecular sieves were
filtered off and the reaction mixture was concentrated under vacuum. The residue was purified by
flash column chromatography (petroleum ether/ethyl acetate 12:1) to obtain 8 (1.32 g, 66%) as a
22
1
colorless syrup. [α]D −96.9° (c 1.0, CHCl3). H NMR (300 MHz, CDCl3): δ 8.20−8.17 (m, 2H,
ArH), 8.11−8.08 (m, 2H, ArH), 7.64−7.57 (m, 2H, ArH), 7.50−7.43 (m, 4H, ArH), 6.02−5.89 (m,
1H, OCH2CHCH2), 5.41 (t, 1H, J = 2.7 Hz, H-3), 5.37−5.21 (m, 2H, OCH2CHCH2), 5.17 (t, 1H, J
= 2.2 Hz, H-4), 5.03 (m, 1H, H-2), 4.98 (s, 1H, H-1), 4.63−4.57 (m, 1H, H-5), 4.15−4.06 (m, 1H,
OCH2CHCH2), 4.34−4.28 (m, 1H, OCH2CHCH2), 2.01 (s, 3H, OCOCH3), 1.32 (d, 3H, J = 6.7 Hz,
H-6); 13C NMR (75 MHz, CDCl3) : δ 169.0 (COMe), 165.1 (COPh), 164.4 (COPh), 133.4, 133.1,
129.7, 129.6, 129.3, 129.1, 128.1, 117.1, 96.7 (C-1), 68.7, 68.3, 67.2, 66.9, 62.1, 20.4, 15.7 (C-6).
ESI-HRMS [M + Na]+ calculated for C25H26NaO8 477.1525 found 477.1521.
4.6. Allyl 3,4-di-O-benzoyl-α-L-talopyranoside (6)
A solution of 8 (1.20 g, 2.64 mmol) in methanol (50 mL) was mixed with acetyl chloride
(1.00 mL, 14.06 mmol) at 0°C in a nitrogenous environment. The reaction mixture was stirred for
10 h, and the completion of the reaction was confirmed by TLC (petroleum ether/ethyl acetate 6:1)
analysis. The reaction was quenched with saturated aqueous NaHCO3 solution (50 mL), diluted
with CH2Cl2 and extracted with CH2Cl2 (3 × 150 mL). The organic phases were combined, dried
over Na2SO4, and concentrated. The residue was purified by flash column chromatography
(petroleum ether/ethyl acetate 8:1) to obtain 8 (0.76 g, 71%) as a colorless syrup. [α]D22 −99.56° (c
1
1.0, CHCl3). H NMR (300 MHz, CDCl3): δ 8.05−8.02 (m, 2H, ArH), 7.92−7.89 (m, 2H, ArH),
7.62−7.56 (m, 1H, ArH), 7.50−7.34 (m, 3H, ArH), 7.33−7.28 (m, 2H, ArH), 6.00−5.87 (m, 1H,
OCH2CHCH2), 5.66 (t, 1H, J = 1.9 Hz, H-3), 5.54 (t, 1H, J = 3.5 Hz, H-4), 5.37−5.22 (4m, 2H,
OCH2CHCH2), 5.05 (d, 1H, J = 1.5 Hz, H-1), 4.34 (m, 1H, H-2), 4.29−4.21 (m, 1H, H-5),
4.11−4.02 (m, 2H, OCH2CHCH2), 2.95 (d, 1H, J = 10.4 Hz, OH), 1.27 (d, 3H, J = 6.5 Hz, H-6);
13C NMR (75 MHz, CDCl3) : δ 165.3 (COPh), 165.0 (COPh), 133.2, 132.8, 129.5, 129.3, 129.2,
129.1, 128.4, 127.9, 117.5, 99.0 (C-1), 77.2, 76.8, 76.3, 71.6, 68.3, 68.0, 67.9, 64.7, 16.0 (C-6).
ESI-HRMS [M + Na]+ calculated for C23H24NaO7 435.1420 found 435.1414.
4.7. 2-O-acetyl-3,4-di-O-benzoyl-L-trichloroacetimidate (7)
A solution of 8 (700 mg, 1.56 mmol) in methanol (20 mL) was mixed with PdCl2 (100 mg).

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The reaction mixture was stirred for 2 h at room temperature, and TLC analysis (petroleum
ether/ethyl acetate 4:1) was performed to identify the completion of the reaction. The residue was
filtered through a pad of Celite, and the filtrate was concentrated. The residue was purified by
flash column chromatography (petroleum ether/ethyl acetate 5:1) to acquire intermediate
compound 15 (600 mg, 80%). A solution of 15 in CH2Cl2 (20 mL) at 0°C under nitrogenous
environment was mixed with trichloroacetonitrile (0.40 mL, 3.91 mmol) and DBU (0.05 mL). The
reaction mixture was stirred for 1 h, and the TLC analysis (petroleum ether/ethyl acetate 6:1)
indicated the completion of the reaction; the reaction mixture was then concentrated. The residue
was subjected to flash column chromatography (petroleum ether/ethyl acetate 10:1) to obtain 7
22
1
(0.70 g, 90%) as a colorless syrup. [α]D −20.7° (c 1.0, CHCl3). H NMR (300 MHz, CDCl3): δ
8.78 (s, 1H, ONHCCl3), 8.21−8.16 (m, 2H, ArH), 7.80−7.77 (m, 2H, ArH), 7.64−7.59 (m, 1H,
ArH), 7.51−7.46 (m, 3H, ArH), 7.34−7.28 (m, 2H, ArH), 6.45 (d, 1H, J = 1.5 Hz, H-1), 5.72−5.68
(m, 2H, H-3, H-4), 5.54−5.52 (m, 1H, H-2), 4.59−4.53 (m, 1H, H-5), 2.07 (s, 3H, COCH3), 1.33
(d, 3H, J = 6.5 Hz, H-6);13C NMR (75 MHz, CDCl3) : δ 169.4 (COMe), 165.4 (COPh), 164.8
(COPh), 159.7, 133.1, 132.9, 129.7, 129.3, 128.9, 128.1, 128.0, 95.5 (C-1), 90.5(OCNHCCl3),
68.5, 67.9, 66.2, 65.3, 20.4, 16.0 (C-6). ESI-HRMS [M + Na]+ calculated for C24H2Cl3NNaO8
580.0309 found 580.0313.
4.8. 2-O-benzyl-3,4,6-tri-O-acetyl-D-trichloroacetimidate (5)
A solution of ethylene diamine: CH3COOH (0.85 mL: 0.85mL v/v) in THF (250 mL) at 0°C
was prepared and a solution of the compound 16 (5.00 g, 11.42 mmol) in THF (50 mL) was added
dropwise to the previous solution. The resultant mixture was stirred for 24 h at room temperature,
and the TLC analysis (petroleum ether/ethyl acetate 2:1) indicated the completion of the reaction.
The reaction was then quenched with 1M HCl (200 mL), and the reaction mixture was extracted
with CH2Cl2 (3 × 100 mL). The combined organic phases were washed with saturated aqueous
NaHCO3 solution (200 mL), and brine (2 × 200 mL), then dried over anhydrous sodium sulfate,
filtered, and concentrated under vacuum. The residue was purified by flash column
chromatography (petroleum ether/ethyl acetate 4:1) to obtain 17 (3.42 g, 77%) as a colorless syrup.
Subsequently, the solution of 17 (3.42 g, 8.62 mmol) in CH2Cl2 (50 mL) at 0°C was mixed with
trichloroacetonitrile (1.26 mL, 12.60 mmol) and DBU (0.1 mL) under a nitrogenous environment.
The reaction mixture was stirred for 1 h and the completion of the reaction was confirmed by TLC
(petroleum ether/ethyl acetate 3:1) analysis. The reaction mixture was concentrated, and the
residue was subjected to flash column chromatography (petroleum ether/ethyl acetate 4:1) to
22
1
obtain 5 (4.19 g, 90%) as a colorless syrup. [α]D 10.2° (c 1.0, CHCl3). H NMR (300 MHz,
CDCl3): δ 8.69 (s, 1H, OCNHCCl3), 7.37−7.27 (m, 5H, BnH), 6.50 (d, 1H, J = 3.6 Hz, H-1), 5.51
(t, 1H, J = 9.7 Hz, H-3), 5.09 (t, 1H, J = 10.0 Hz, H-4), 4.65 (d, 2H, J = 12.3 Hz, CH2Ph),
4.31−4.25 (m, 1H, H-6), 4.23−4.17 (m, 1H, H-5), 4.11−4.06 (m, 1H, H-6), 3.79 (dd, 1H, J1 = 3.6
Hz, J2 = 9.9 Hz, H-2), 2.06, 2.05, 2.02 (3s, 9H, OCOCH3); 13C NMR (75 MHz, CDCl3) : δ 170.5,
169.9, 169.7, 161.0, 137.3, 128.5, 128.0, 127.7, 93.34 (C-1), 90.9, 75.8, 72.9, 71.5, 69.9, 68.0,
61.6, 20.7, 20.6, 20.6. ESI-HRMS [M + NH4]+ calculated for C21H28Cl3N2O9 557.0860 found
557.0851.
4.9. Allyl 2-O-benzyl-3,4,6-tri-O-acetyl-α-D-glucopyranosyl-(1→2)-3,4-di-O-benzoyl-α-L-
talopranoside (18)
A mixture of 5 (1.00 g, 2.43 mmol), 6 (1.35 g, 2.50 mmol), and 4 Å MS (0.4 g) in anhydrous

ACCEPTED MANUSCRIPT
CH2Cl2 (30 mL) was stirred at room temperature for 30 min under a N2 atmosphere. The mixture
was cooled to −25°C, and then TMSOTf (10 μL) was added. Again, the mixture was stirred at
the same temperature for 8 h. The completion of the reaction was identified by TLC analysis
(petroleum ether/ethyl acetate 3:1). The reaction was quenched with Et3N, and the mixture was
diluted with CH2Cl2 (10 mL), filtered through a pad of celite, and the filtrate was concentrated.
The residue was purified by flash column chromatography (petroleum ether/ethyl acetate 4:1) to
22
1
yield 18 (1.93 g, 74%) as a colorless syrup. [α]D 8.2° (c 1.0, CHCl3). H NMR (300 MHz,
CDCl3): δ 8.24−8.21 (m, 2H, ArH), 7.95−7.92 (m, 2H, ArH), 7.52−7.46 (m, 2H, ArH), 7.39−7.27
(m, 9H, ArH), 5.95−5.82 (m, 1H, OCH2CHCH2), 5.60−5.57 (m, 2H, H-3, H-4), 5.37 (t, 1H, J =
9.7 Hz, H-3), 5.28−5.18, (m, 2H, OCH2CHCH2), 5.09 (s, 1H, H-1-Talp), 4.94 (d, 1H, J = 3.7 Hz,
H-1), 4.80 (t, 1H, J = 10.2 Hz, H-4), 4.66 (dd, 2H, J1 = 11.7 Hz, J2 = 11.7 Hz, CH2Ph), 4.32−4.25
(m, 1H, H-5), 4.22−4.16 (m, 1H, OCH2CHCH2), 4.09−4.03 (m, 1H, H-2), 3.99−3.93 (m, 1H,
OCH2CHCH2), 3.88−3.85 (m, 1H, H-5), 3.65−3.54 (m, 2H, H-6), 3.17 (dd, 1H, J1 = 2.0 Hz, J2 =
12.5 Hz, H-2), 1.98, 1.86, 1.78, (3s, 9H, OCOCH3), 1.28 (d, 3H, J = 6.5 Hz, H-6); 13C NMR (75
MHz, CDCl3) : δ 169.9 (COMe), 169.3 (COMe), 169.2 (COMe), 166.2 (COPh), 166.1 (COPh),
137.4, 133.3, 132.9, 132.5, 129.9, 129.5, 129.2, 129.2, 128.3, 128.2, 128.1, 127.7, 127.7, 117.3,
96.98 (C-1), 96.72 (C-1), 72.9, 72.9, 71.9, 68.3, 68.0, 67.9, 67.5, 67.2, 64.9, 60.7, 20.5 (COMe),
20.3 (COMe), 20.1 (COMe), 16.0 (C-6). ESI-HRMS [M + NH4]+ calculated for C42H50NO15
808.3180 found 808.3170.
4.10.
2,3,4,6-tetra-O-acetyl-α-D-glucopyranosyl-(1→2)-3,4-di-O-benzoyl-α/β-L-talopranoside
(20)
A solution of 18 (1.60 g, 2.02 mmol) in methanol (25 mL) was mixed with PdCl2 (180 mg).
The reaction mixture was stirred for 2 h at room temperature. The completion of the reaction was
identified by TLC analysis (petroleum ether/ethyl acetate 2:1). The reaction mixture was filtered
through a pad of Celite, and the filtrate was concentrated. The residue was purified by flash
column chromatography (petroleum ether/ethyl acetate 4:1) to obtain 19 (1.31 g, 86%). The
resultant compound 19 was dissolved in methanol (75 ml), and mixed with 10% Pd/C (0.4 g).
Hydrogen gas was passed through the mixture and the reaction was continued for 48 h. The
completion of the reaction was identified by TLC analysis (petroleum ether/ethyl acetate 1:2). The
reaction mixture was filtered through a pad of celite, and the filtrate was concentrated to obtain a
yellow syrup. The resultant syrup was subsequently dissolved in pyridine (20 mL) at 0°C in a N2
environment. The reaction mixture was stirred for 5 min, and acetyl chloride (0.59 mL, 8.35
mmol) in CH2Cl2 (5 ml) was added dropwise. The resultant mixture was stirred for another 4 h at
room temperature, and TLC analysis (petroleum ether/ethyl acetate 2:1) was performed to identify
the completion of the reaction. The reaction was then quenched with chilled H2O (50 mL), and
extracted with CH2Cl2 (3 ×25 mL). The organic phases were combined, dried over Na2SO4, and
concentrated. The residue was purified by flash column chromatography (petroleum ether/ethyl
22
acetate 3:1) to obtain 20 (1.13 g, 70% from 18) as a colorless syrup. [α]D 14.1° (c 1.0, CHCl3).
1H NMR (300 MHz, CDCl3): δ 8.29−8.21 (m, 2H, ArH), 7.90−7.82 (m, 2H, ArH), 7.58−7.25 (m,
6H, ArH), 6.19 (d, 0.5 H, J = 1.0 Hz, Hβ-1-Talp), 5.77 (s, 0.5H, Hα-1-Talp)，5.65 (d, 0.5 H, J =
4.0Hz, H-1-Glcp), 5.24 (d, 0.5 H, J = 4.0 Hz, H-1-Glcp), 2.15−1.73 (m, 15H, OCOCH3); 13C
NMR (75 MHz, CDCl3): δ 96.25 (C-1-Talp), 94.68 (C-1-Talp), 92.33 (C-1-Glcp), 91.64
(C-1-Glcp). ESI-HRMS [M + NH4]+ calculated for C36H44NO17 762.2609 found 762.2611.
4.11. 2,3,4,6-tetra-O-acetyl-α-D-glucopyranosyl-(1→2)-3,4-di-O-benzoyl-α-L-

ACCEPTED MANUSCRIPT
trichloroacetimidate (3)
A solution of ethylene diamine: CH3COOH (0.17 mL: 0.17 mL v/v) in THF (40 mL) was
prepared and a solution of compound 20 (0.70 g, 0.99 mmol) in THF (10 ml) was added dropwise
at 0°C to the previous solution. The resultant mixture was stirred for 12 h at room temperature.
The completion of the reaction was identified by TLC analysis (petroleum ether/ethyl acetate 5:1).
The reaction was then quenched with 1M HCl (200 mL), and the reaction mixture was extracted
with CH2Cl2 (3 × 100 mL). The organic phases were washed with saturated aqueous solution of
NaHCO3 (200 mL), and brine (2 × 200 mL), then dried over anhydrous sodium sulfate, filtered,
and concentrated under vacuum. The residue was purified by flash column chromatography
(petroleum ether/ethyl acetate 8:1) to obtain compound 21 (0.60 g, 87%). Subsequently, a solution
of 21 (0.55 g, 0.78 mmol) in CH2Cl2 (10 mL) at 0°C in a N2 environment was mixed with
trichloroacetonitrile (0.195 mL, 1.95 mmol) and DBU (10 µL). The reaction mixture was stirred
for 1 h and then concentrated. The residue was subjected to flash column chromatography
22
(petroleum ether/ethyl acetate 4:1) to obtain 3 (0.55 g, 95%) as a colorless syrup. [α]D 16.6° (c
1
1.0, CHCl3). H NMR (300 MHz, CDCl3): δ 8.70 (s, 1H, OCNHCCl3), 8.30−8.28 (m, 2H, ArH),
7.93−7.90 (m, 2H, ArH), 7.62−7.50 (m, 4H, ArH), 7.38−7.33-7.38 (m, 2H, ArH), 6.38 (s, 1H, H-1-
Talp), 5.69 (m, 1H, H-4), 5.64 (t, 1H, J = 4.1 Hz, H-3), 5.46 (t, 1H, J = 9.7 Hz, H-3), 5.37 (d, 1H,
J = 4.1 Hz, H-1-Glcp), 4.95−4.88 (m, 2H, H-6), 4.54 (dd, 1H, J1 = 5.9 Hz, J2 = 13.7 Hz, H-2),
4.30 (d, 1H, J = 4.5 Hz, H-5), 3.92−3.86 (m, 1H, H-5), 3.52 (dd, 1H, J1 = 3.7 Hz, J2 = 12.6 Hz,
H-2), 3.12 (dd, 1H, J1 = 2.1 Hz, J2 = 12.6 Hz, H-2), 2.18, 2.02, 1.86, 1.79 (4s, 12H, OCOCH3),
1.31 (d, 3H, J = 6.5 Hz, H-6);13C NMR (75 MHz, CDCl3) : δ 170.0 (COMe), 169.9 (COMe),
169.4 (COMe), 168.9 (COMe), 166.0 (COPh), 164.9 (COPh), 133.3, 132.9, 129.7, 129.5, 129.0,
129.8, 128.6, 128.3, 96.11 (C-1-Talp)), 96.07 (C-1-Glcp), 90.37 (OCNHCCl3), 71.1, 70.6, 70.2,
68.3, 68.2, 67.7, 67.1, 66.8, 60.3, 20.38 (2×COMe), 20.12 (COMe), 20.09 (COMe), 16.05 (C-6).
ESI-HRMS [M + NH4]+ calculated for C36H42Cl3N2O16 863.1600 found 863.1591.
4.12. Allyl 2-O-acetyl-3,4-di-O-benzoyl-α-L-talopyranosyl-(1→2)-3,4-di-O-benzoyl-α-L-
talopyranoside (22)
A mixture of 6 (0.50 g, 1.21 mmol), 7 (0.71 g, 1.25 mmol), and 4 Å MS (0.2 g) in anhydrous
CH2Cl2 (20 mL) was stirred at room temperature for 30 min in a N2 atmosphere. The mixture was
cooled to 0°C, followed by addition of TMSOTf (2 µL). The resultant mixture was stirred at 0°C
for 3 h. The completion of the reaction was monitored by TLC analysis (petroleum ether/ethyl
acetate 5:1). The reaction was then quenched by adding Et3N. The reaction mixture was diluted
with CH2Cl2 (10 mL), filtered through a pad of celite, and the filtrate was concentrated. The
residue was purified by flash column chromatography (petroleum ether/ethyl acetate 7:1) to obtain
22 (0.76 g, 75%) as a colorless syrup. [α]D22 −51.0° (c 1.0, CHCl3). 1H NMR (300 MHz, CDCl3):
δ 8.09−8.05 (m, 4H, ArH), 7.88−7.86 (m, 2H, ArH), 7.77−7.74 (m, 2H, ArH), 7.57−7.47 (m, 4H,
ArH), 7.42−7.26 (m, 8H, ArH), 6.02−5.89 (m, 1H, OCH2CHCH2), 5.66−5.63 (m, 2H, H-3, H-4),
5.60−5.58 (m, 2H, H-3, H-4), 5.41−5.27 (m, 2H, OCH2CHCH2), 5.15 (d, 1H, J = 3.7 Hz, H-2),
5.08 (s, H, H-1), 5.09 (s, 2H, H-1), 4.55−4.48 (m, 1H, H-5), 4.38−4.26 (m, 2H, H-2, H-5),
4.16−4.10 (m, 2H, OCH2CHCH2), 1.88 (s, 3H, OCOCH3), 1.32,1.27 (2d, 6H, J = 6.5 Hz, H-6,
H-6); 13C NMR (75 MHz, CDCl3) : δ 169.0 (COMe), 166.1(COPh), 165.5 (COPh), 165.1 (COPh),
164.8 (COPh), 133.05, 133.0, 132.9, 132.8, 132.7, 129.6, 129.6, 129.4, 129.3, 129.2, 129.2, 129.0,
128.2, 128.1, 128.0, 128.0, 117.65, 100.14 (C-1), 98.05 (C-1), 73.3, 69.1, 68.9, 67.9, 67.8, 66.7,
66.5, 64.8, 20.4, 16.0 (C-6, C-6). ESI-HRMS [M + Na]+ calculated for C45H45NaO14 831.2629
found 831.2633.

ACCEPTED MANUSCRIPT
4.13. Allyl 3,4-di-O-benzoyl-α-L-talopyranosyl-(1→2)-3,4-di-O-benzoyl-α-L-talopyranoside (4)
A solution of 22 (600 mg, 0.78 mmol) in anhydrous CH2Cl2/MeOH (30 mL) was mixed with
acetyl chloride (1.0 mL) portion-wise at 0°C. The mixture was stirred at room temperature for
10 h, until the TLC analysis (petroleum ether/ethyl acetate 4:1) showed that the reaction was
complete. The solution was neutralized with saturated aqueous NaHCO3 solution and extracted
with dichloromethane (2 × 30 mL). The organic phases were combined, dried over anhydrous
Na2SO4, and concentrated under reduced pressure to dryness. The residue was subjected to
column chromatography (petroleum ether/ethyl acetate 6:1) to obtain 4 (0.50 g, 83%) as a
22
1
colorless syrup. [α]D −13.7° (c 1.0, CHCl3). H NMR (300 MHz, CDCl3): δ 8.04−8.02 (m, 2H,
ArH), 7.96−7.89 (m, 6H, ArH), 7.60−7.49 (m, 3H, ArH), 7.45−7.34 (m, 6H, ArH), 7.30−7.23 (m,
3H, ArH), 7.17−7.12 (m, 1H, ArH), 6.03−5.90 (m, 1H, OCH2CHCH2), 5.72 (d, 1H, J = 3.2 Hz,
H-4), 5.65 (t, 1H, J = 3.7 Hz, H-3), 5.59 (m, 1H, H-4), 5.50 (t, 1H, J = 3.5 Hz, H-3), 5.41−5.27 (m,
2H, OCH2CHCH2), 5.19 (s, 1H, H-1), 5.10 (s, 1H, H-1), 4.55−4.51 (m, 1H, H-5), 4.37−4.26 (m,
2H, H-2, H-5), 4.16−4.07 (m, 2H, OCH2CHCH2), 3.75 (dd, 1H, J1 = 1.9 Hz, J2 = 10.4 Hz, H-2),
2.75 (d, 1H, J = 10.4 Hz, OH), 1.31, 1.27, (2d, 6H, J = 6.5 Hz, H-6, H-6); 13C NMR (75 MHz,
CDCl3) : δ 165.9 (COPh), 165.2 (COPh), 165.1 (COPh), 164.9 (COPh), 133.2 (OCH2CHCH2),
133.1, 132.9, 132.7, 129.5, 129.4, 129.3, 129.2, 129.2, 129.1, 128.9, 128.7, 128.4, 128.2, 128.1,
128.0, 117.6 (OCH2CHCH2), 102.63 (C-1), 98.17 (C-1), 73.4, 71.3, 69.2 (OCH2CHCH2), 68.2,
67.9, 65.2, 64.8, 16.0, 15.9. ESI-HRMS [M + NH4]+ calculated for C43H46NO13 784.2969 found
784.2974.
4.14. Allyl 2,3,4,6-tetra-O-acetyl-α-
talopyranosyl-(1→2)-3,4-di-O-benzoyl-α-
-talopyranoside (23)
A mixture of 3 (0.50 g, 0.59 mmol), 4 (0.44 g, 0.58 mmol), and 4 Å MS (0.2 g) in anhydrous
D
-glucopyranosyl-(1→2)-3,4-di-O-benzoyl-α-
L-
L-talopyranosyl-(1→2)-3,4-di-O-benzoyl-α-
L
CH2Cl2 (20 mL) was stirred at 25°Cfor 30 min under a N2 atmosphere and cooled to −10°C,
followed by addition of TMSOTf (5 µL) to the mixture. The mixture was stirred at −10°C for 12 h
until the TLC analysis (petroleum ether/ethyl acetate 5:1) indicated completion of the reaction.
The reaction mixture was neutralized with Et3N, diluted with CH2Cl2 (10 mL), filtered through a
pad of celite, and the filtrate was concentrated. The residue was purified by flash column
chromatography (petroleum ether/ethyl acetate 3:1) to obtain 23 (0.54 g, 66%) as a colorless
22
1
syrup. [α]D −86.4° (c 1.0, CHCl3). H NMR (300 MHz, CDCl3): δ 8.08−7.95 (m, 5H, ArH),
7.92−7.83 (m, 5H, ArH), 7.57−7.48 (m, 5H, ArH), 7.48−7.42 (m, 5H, ArH), 7.39−7.27 (m, 10H,
ArH), 6.02−5.89 (m, 1H, OCH2CHCH2), 5.64−5.61 (m, 4H, H-3, H-3, H-4, H-4), 5.54−5.49 (m,
1H, H-3), 5.50−5.32 (m, 2H, OCH2CHCH2), 5.39−5.36 (t, 1H, J = 4.2 Hz, H-3), 5.34−5.27 (m,
2H, H-4, H-4), 5.24 (s, 1H, H-1-Talp1), 5.13 (s, 1H, H-1-Talp2), 4.87−4.81 (t, 1H, J = 10.0 Hz,
H-2), 4.75 (s, 1H, H-1-Talp3), 4.68 (d, 1H, J = 3.9 Hz, H-1-Glcp), 4.63−4.54 (m, 2H, H-2, H-2),
4.42−4.27 (m, 3H, H-2, H-5, H-5), 4.17−4.15 (m, 2H, OCH2CHCH2), 3.89−3.88 (m, 1H, H-5),
3.82−3.81 (m,1H, H-5), 3.72−3.68, 3.48−3.43 (2m, 2H, H-6), 1.94, 1.83, 1.72, 1.61, (4s, 12H,
OCOCH3)，1.31 (d, 3H, J = 6.5 Hz, H-6), 1.32 (d, 3H, J = 6.4 Hz, H-6), 0.73 (d, 3H, J = 6.5 Hz,
H-6); 13C NMR (75 MHz, CDCl3) : δ 167.8 (COMe), 169.2 (COMe), 169.1 (COMe), 168.9
(COMe), 165.9 (COPh), 165.8 (COPh), 165.7 (COPh), 165.5 (COPh), 165.0 (COPh), 164.7
(COPh), 133.1 (OCH2CHCH2), 133.0, 129.7, 129.4, 129.3, 129.2, 128.3, 128.3, 117.8
(OCH2CHCH2), 101.6 (C-1-Talp1), 99.7 (C-1-Talp2), 97.9 (C-1-Talp3), 95.1 (C-1-Glcp), 76.9,

ACCEPTED MANUSCRIPT
74.8, 74.6, 72.3, 70.0 (OCH2CHCH2), 69.4, 68.9, 68.5, 68.2, 67.9, 67.7, 67.3, 67.2, 66.7, 65.4,
65.3, 64.9, 60.2, 20.3, 20.2, 20.1, 20.0, 19.8, 16.0, 15.5. ESI-HRMS [M + NH4]+ calculated for
C77H82NO28 1468.5023 found 1468.5074.
4.15. Ally α-D-glucopyranosyl-(1→2)-α-L-talopyranosyl-(1→2)-α-L-talopyranosyl-(1→2)-α-L-
talopyranoside (2)
A solution of 23 (400 mg, 0.28 mmol) in methanol (10 mL) was mixed with 40 mLsaturated
MeOH-NH3 solution. The resultant mixture was stirred for 14 days and the solvent was removed
under reduced pressure to obtain 2 (127 mg, 70%) as a yellow syrup. [α]D22 −20.5° (c 1.0, MeOH).
1H NMR (300 MHz, D2O): δ 5.93−5.81 (m, 1H, OCH2CHCH2), 5.31−5.22 (m, 2H, OCH2CHCH2),
5.06 (s, 2H, H-1-Talp1, H-1-Talp2), 4.94 (d, 1H, J = 3.7 Hz, H-1-Glcp), 4.87 (s, 1H, H-1-Talp3),
4.17−3.32 (m, 19H), 1.20−1.16 (m, 9H, H-6); 13C NMR (75 MHz, D2O) : δ 132.9 (OCH2CHCH2),
118.6 (OCH2CHCH2), 101.7 (C-1-Talp1), 100.4 (C-1-Talp2), 97.5 (C-1-Glcp), 97.2 (C-1-Talp3),
76.8, 76.7, 73.6, 72.4, 71.8, 71.2, 71.0, 70.8, 70.7, 69.3, 67.9, 67.6, 67.3, 66.8, 65.6, 65.2, 65.1,
60.2, 15.24, 15.19. ESI-HRMS [M + NH4]+calculated for C27H50NO18 676.3028 found676.3035.
Acknowledgments
This work was partially supported by the NSFC (21772230) and the National S & T
Pillar Program (2015BAK45B01) of China.
Supplementary Data
Supplementary data associated with this article can be found, in the online version, at
http://~~.
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Highlights:
1. we have reported a convergent total synthesis of a tetrasccharide analogue
2. Stereo- and regio-specific synthesis was achieved in Schmidt glycosylation employing
appropriately protected L-talopyranosyl and D-glucopyranosyl building blocks to build a
disaccharide containing α-Glcp-(1→2)-6dTalp configured glycosidic bonds.
3. The synthesis involves an allyloxyethylidene group for protecting rhamnopyranose 1-OH and
2-OH at the same time, a redox reaction of rhamnopyranoside derivative for the synthesis of
6-deoxy talopyranoside.