A Highly α-Stereoselective Sialylation Method Using 4-O-4-Nitropicoloyl Thiosialoside Donor

Article abstract of DOI:10.1002/ejoc.201901587

An efficient α-sialylation methodology for various primary, secondary, and tertiary alcohol acceptors has been developed. The sialic acid ethyl thioglycoside 1b, bearing a 4-nitropicoloyl moiety as the stereodirecting group at the C4 position, was utilized as the glycosyl donor, and the sialylation reaction was activated with N-iodosuccinimide and catalytic triflic acid in a 1:1 mixture of dichloromethane/acetonitrile as solvent. The method was successfully applied to the stereocontrolled synthesis of protected trisaccharide 11 found in the repeating unit of serotype Ia Group B Streptococcus capsular polysaccharide.

Full text of DOI:10.1002/ejoc.201901587

A Journal of
Accepted Article
Title: A Highly α-Stereoselective Sialylation Method Using 4-O-4-
Nitropicoloyl Thiosialoside Donor
Authors: Dong-Mei Liu, Hong-Ling Wang, Jin-Cai Lei, Xian-Yang Zhou,
and Jinsong Yang
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To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201901587
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10.1002/ejoc.201901587
European Journal of Organic Chemistry
A Highly -Stereoselective Sialylation Method Using 4-O-4-Nitropicoloyl Thiosialoside Donor
Dong-Mei Liu, Hong-Ling Wang, Jin-Cai Lei, Xian-Yang Zhou, and Jin-Song Yang*
Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province,
Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision
Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China
Corresponding Author. E-mail address: yjs@scu.edu.cn (J.-S. Yang)
TOC
Abstract: An efficient -sialylation methodology for various primary, secondary, and tertiary alcohol acceptors has
been developed. The sialic acid ethyl thioglycoside 1b, bearing a 4-nitropicoloyl moiety as the stereodirecting group
at the C4 position, was utilized as the glycosyl donor, and the sialylation reaction was activated with
N-iodosuccinimide and catalytic triflic acid in a 1:1 mixture of dichloromethane/acetonitrile as solvent. The method
was successfully applied to the stereocontrolled synthesis of protected trisaccharide 11 found in the repeating unit of
serotype Ia Group B Streptococcus capsular polysaccharide.
Introduction
Sialic acid (Neu5Ac), an acidic nine carbon saccharide, usually terminates the carbohydrate portions of
glycoproteins and glycolipids of mammals as an -glycoside. These glycoconjugates play a central role in cell
surface recognition phenomena.[1] Chemical synthesis of structurally defined sialic acid-containing glycans is highly
desirable as the synthetic molecules play significant roles in developing potential carbohydrate-based vaccines or
diagnostics.[2] Numerous glycosylation methods have been developed for efficient -sialylation,[3] including the use
of various anomeric leaving groups,[4] such as halides,[4a,b] N-phenyltrifluoroacetimidates,[4c] thioglycosides,[4d]
phosphites,[4e] phosphates,[4f] C2-hemiketals,[4g] and ortho-hexynylbenzoates,[4h,i] the introduction of novel protecting
groups,[5] the installation of an auxiliary group at the C1 or C3 position,[6] as well as the utility of solvent effect.[7]
Among the sialyl donors employed to date, the 5-N,4-O-oxazolidinone substituted sialyl donors, originally reported
by Takahashi et al.,[5g] showed special power in the stereoselective construction of -sialic acid linkage. Moreover,
the macrobicyclized sialic acid donors[5i] and the 1-picolinyl-5-azido thiosialoside donors[6i] recently developed by
Ando and Sun groups, respectively, are also effective for the -sialylation of diverse acceptors. But a facile and
general silalylation approach with high -stereoselectivity still has not been fully achieved. The major problem
encountered in silalylation is that the absence of a C3 participating group is not able to guarantee the stereocontrol of
glycosylation. Another problem is that the presence of the C1 electron-withdrawing carboxylic group reduces the
reactivity of a typical sialic acid donor, thereby leading to a low glycosylation yield and formation of a significant
amount of undesirable 2,3-glycal side product.
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Recently, a novel hydrogen-bonding-mediated aglycone delivery (HAD) glycosylation strategy was reported by the
Demchenko group.[8] In a typical HAD reaction, the suitably 2-pyridinecarbonyl (Pico) or 2-pyridinemethyl (Pic)
substituted glycosyl donors are employed to couple with acceptors. Guided by the intermolecular hydrogen bonding
formed between the sp2-hybridized nitrogen of Pico or Pic group and the hydroxyl group of acceptor, the
nucleophilic attack of acceptor to the anomeric center of donor proceeds in a highly stereocontrolled manner, thus
leading to stereoselective formation of a glycoside product. Based on the HAD strategy, our laboratory[9] established
a 2-quinolinecarbonyl (Quin)-assisted glycosylation protocol for stereoselective assembly of a series of challenging
glycosides including -arabino-[9a] and -galactofuranosides,[9b] -3-deoxy-D-manno-oct-2-ulosonic acid (Kdo)
glycoside,[9c] and -L-rhamnopyranoside.[9d]
The HAD strategy was first applied by De Meo et al. to the stereoselective generation of -sialoside.[10a] They found
that up to 14:1 / ratio was gained in the coupling of 4-O-Pico substituted phenylthio sialyl donors with primary
galactose alcohol in the presence of an excess of triflic acid (TfOH, 2.0 equiv per 1 equiv of donor). Besides, a new
-sialylation reaction using 7,8-di-O-picoloylated sialyl thioglycoside as donor was reported by Tsai and
co-workers.[10b] However, in both works, the acceptor scope was only limited to primary alcohols such as 6-OH
glycosides. In the glycosylation of secondary acceptors, no desired coupling glycoside but 2,3-dehydro byproduct
was observed.
Here, we report an efficient -stereoselective synthesis of sialyl glycosides using 4-O-(4-nitropicoloyl) substituted
sialic acid ethyl thioglycoside as glycosyl donor under the activation of N-iodosuccinimide (NIS) and catalytic TfOH
in dichloromethane (CH2Cl2)/acetonitrile (CH3CN) (1:1, v/v) co-solvent at -78 to -30 °C. Compared to the existing
HAD-based sialylation reactions mentioned above, our means can be applied in diverse acceptor substrates and
afforded the corresponding -linked sialosides in satisfactory chemical yield. The efficiency the method possesses is
further demonstrated by the facile preparation of protected sialylated trisaccharide derived from the capsular
polysaccharide (CPS) of serotype Ia group B Streptococcus (GBS).
Results and Discussion
Scheme 1. Design of potential sialyl donor for -glycosylation.
First, the effectiveness of hydrogen bond as a stereocontrolling factor on the sialylation stereochemistry was
investigated. Thus, two ethylthio sialyl donors 1a,b having a Pico or a 4-nitropicoloyl moiety, respectively, as the
stereodirecting function on the C4 position were designed and synthesized (Table 1). As shown in Scheme 1, we
envisioned that the intermolecular hydrogen bonding formed between the donor and the acceptor would direct the
nucleophilic addition of acceptor on the oxocarbenium ion intermediate from the -face, hence resulting in an
-linked glycoside. For the purpose of comparison, donor 1c carrying a benzoyl (Bz) instead of Pico group on the
C4 position was also prepared. The comparative testing of sialyl donors 1a-c with model acceptor molecule, the
galactose 3,4-diol 2,[11] was carried out under the promotion of NIS (1.5 equiv) and a catalytic amount of TfOH (0.1
equiv) reagent system at -78 to -30 °C using CH2Cl2 or CH2Cl2/CH3CN (1:1, v/v) as solvent, and the results are
summarized in Table 1. First, we examined the sialylation between picoloylated 1a and 2 in different solvents. When
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European Journal of Organic Chemistry
performed in CH2Cl2, the glycosylation gave rise to the desired (2,3)-linked sialoside product 3a in only 20% yield
with very low diastereoselectivity (/ 2:1), along with 87% yield of elimination byproduct 4a (Table 1, entry 1).
The stereochemistry of the obtained sialoside products was confirmed by the measurement of the long-range
coupling constant 3JC1-H3ax of the sialic acid residue.[12] We were pleased to find that when CH2Cl2/CH3CN (1:1) was
used as solvent, both the sialylation yield and selectivity were enhanced (40%, / 6:1, entry 2).[13] So, using
CH2Cl2/CH3CN (1:1) as solvent, we next studied the sialylations of donors 1b,c with 2. As a result, the product yield
and selectivity obtained in the sialylation of the 4-O-4-nitropicoloyl 1b were much higher than those obtained in the
condensation of the 4-O-picoloyl counterpart 1a (56%, / 15:1, entry 3 vs 40%, / 6:1, entry 2), which suggests
that 1b is more reactive and -selective than 1a. On the other hand, the sialylation of the 4-O-Bz substituted 1c with
2 exhibited poor stereoselectivity even in CH2Cl2/CH3CN (1:1) co-solvent, affording disaccharide 3c in 65% yield as
a pair of / (5:1) anomers (Table 1, entry 4). Overall, the above experimental results clearly indicate that (1) the
combined use of C4 Pico or 4-nitropicoloyl groups and the CH2Cl2/CH3CN solvent system is the crucial factor for
the glycosylation of donors 1a,b; (2) the best results are achieved with 4-O-4-nitropicoloyl equipped thiosialoside 1b,
utilizing NIS/TfOH (cat.) activation in CH2Cl2/CH3CN (1:1) co-solvent at -78 to -30 °C.
Table 1. Glycosylation between donors 1a-c and acceptor 2.a
aGlycosylations were conducted with sialyl donor (2.0 equiv), acceptor (1.0 equiv), NIS (1.5 equiv)/TfOH (0.1
equiv), 4 Å molecular sieves (MS) in anhydrous CH2Cl2 or CH2Cl2/CH3CN (1:1) (100 mM). bIsolated yield based on
the acceptor. cDetermined by 1H NMR of the corresponding isomer mixture. dBased on the donor.
Table 2. -Selective glycosylation of donor 1b with various acceptors.a
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aGlycosylations were conducted with sialyl donor (1.5 and 2.0 equiv for entries 1-8 and 9-17, respectively), acceptor
b
(1 equiv), NIS (1.5 equiv)/TfOH (0.1 equiv), 4 Å MS in anhydrous CH2Cl2/CH3CN (1:1) (100 mM). Isolated yield
based on the acceptor. cDetermined by 1H NMR of the corresponding isomer mixture. dBased on the donor.
With the optimal glycosylation conditions, we then set out to survey a series of acceptors to establish the generality
of this -sialylation reaction. First, the glycosylation of donor 1b with primary acceptors was evaluated.
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Regioselective sialylation of galactose 2,6-diol 5a[14] with 1b under the optimized conditions afforded the desired
sialylated (2,6)-disaccharide 6a with complete  stereoselectivity and excellent yield (Table 2, entry 1). Moreover,
sialylation of other primary acceptors, including glucose 6-OH alcohol 5b,[15] arabinofuranose 5-OH alcohol 5c[16] as
well as non-carbohydrate nucleophile 5d[17] also proceeded smoothly to furnish the corresponding coupling products
6b-d, respectively, in high yields with excellent -selectivity (82-89% yield, / 15:1 to  only, Table 2, entries 2-4).
However, the glycosylations of the primary 2-amino-2-deoxy-D-galactose 6-OH and sialic acid 9-OH acceptors were
affected by the protection pattern. As outlined by Table 2, entries 5-6, exclusive -stereocontrol was realized in the
sialylations of N-acetyl and N-phthalimido protected 2-amino-2-deoxy-D-galactosyl acceptors 5e, f with 1b, but the
former glycosylation (5e with 1b) generated the corresponding sialylated disaccharide 6e in 30% yield only while
the latter (5f with 1b) led to a higher degree of yield (82%) of Neu5Ac(2,6)GalN disaccharide derivative 6f.
Additionally, in the coupling of 5-N,4-O-diacetyl protected sialyl 8,9-diol 5g with 1b, we did not obtain the desired
disaccharide (i.e., 6g) but obtained the 2,3-dehydro side product 4b only, which was probably due to the low
reactivity of the nucleophile (Table 2, entry 7). On the other hand, the silalylation between the sialyl 7,8,9-triol 5h
having a cyclic 5-N,4-O-oxazolidinone protection and 1b occurred at the more reactive 9-OH and provided excellent
90% yield of the desired (2,9)-linked sialic acid dimer 6h as a single  stereoisomer (entry 8). Next, the
condensation of 1b with secondary and tertiary acceptors was studied. The glycosylation outcomes were also
influenced by the nature of the acceptors. For example, the regioselective glycosylation of the galactose 3,4-diol
acceptor 5i with 1b yielded the corresponding Neu5Ac(2,3)Gal disaccharide derivative 6i in 52% yield with
exclusive  selectivity (Table 2, entry 9), but the coupling of fucose 3-OH alcohol 5j[18] with 1b provided the
disaccharide 6j with poor -selectivity (55%, / 5:1, Table 2, entry 10). Stereoselective construction of the (2,8)
linkage between sialic acids is extremely challenging as the hydrogen bonding with the adjacent acetamide function
reduces the reactivity of 8-OH.[19] Reaction of both sialic acid 8-OH alcohol 5k and 7,8-diol 5l with 1b resulted in
unwanted elimination rather than sialylation, forming the sialyl glycal derivatives as the sole products (entries 11 and
12, respectively). However, when 1b was sialylated with 7,8-O-unprotected 5-acetyl 2,3-dehydroneuraminic acid
derivative 5m, the expected (2,8)-linked sialoside 6m was obtained in 40% yield with poor -selectivity (40%, /
4:1, entry 13). Modification of the C5 substituent of the acceptor to N-trifluoroacetyl (TFA) group led to a significant
improvement in stereocontrol ( only, entry 14).[5c] The 7,8-O-unprotected 2,3-dehydroneuraminic acid derivative
has been also successfully utilized as acceptor by Schmidt et al. for the synthesis of (2,8)-disialoside derivatives.[6e]
Moreover, the non-carbohydrate substrates including isopropanol 5o, especially the sterically hindered adamantanols
5p,q all underwent efficient sialylation with 1b to produce the corresponding glycoside products 6o-q in
good-to-excellent yields as predominantly or exclusively -isomers.
In order to demonstrate the utility of this approach in the synthesis of sialic acid-containing oligosaccharide, we
decided to synthesize the sialylated trisaccharide 11 (Scheme 2). This trisaccharide molecule, possessing a
NeuAc(2,3)Gal(1,4)GlcNAc sequence, is a structural fragment found in the serotype Ia GBS CPS.[20] Our
synthesis of the target started with the assembly of the highly demanding -sialic acid linkage. Previously, the
synthesis of this trisaccharide portion was reported by Guo et al. in which the challenging sialic bond was
constructed by a sialyl phosphate donor method.[21] In this work, the newly developed thiosialyl donor 1b was
employed as the key building block for the -sialoside formation. As outlined by Scheme 2, -glycoconjugation of
1b with p-methoxyphenyl 2,6-di-O-(2-naphthylmethyl)--D-galactopyranoside (5i) provided sialylated disaccharide
6i in 52% yield with complete -selectivity. Thereafter, the two 2-naphthylmethyl (Nap) protecting groups in 6i was
readily removed by treatment with 2,3-dichloro-5,6-dicyanobenzo-1,4-quinone (DDQ) to give the disaccharide triol
7 in 91% yield. This compound was acylated with benzoyl chloride (BzCl) and catalytic 4-dimethylaminopyridine
(DMAP) in pyridine/CH2Cl2 to deliver 8 in 85% yield. Disaccharide 8 was subsequently converted into the desired
trichloroacetimidate 9 as an inseparable / (1:1) isomers (51% over two steps) by deprotection of
1-O-p-methoxyphenyl group with ceric ammonium nitrate (CAN) in wet CH2Cl2/CH3CN at room temperature and
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followed by imidation with trichloroacetonitrile (CCl3CN) and 1,8-diazabicyclo-[5.4.0]undec-7-ene (DBU) at 0 °C.
Finally, the resulting sialodisaccharide donor 9 and monosaccharide alcohol 10[22] was condensed under the
activation of trimethylsilyl trifluoromethanesulfonate (TMSOTf) in CH2Cl2 at -78 °C, leading to the formation of the
target trisaccharide 11 in 51% yield and with exclusive -selectivity.
Scheme 2. Synthesis of protected trisaccharide 11.
Conclusions
In conclusion, a novel approach toward -D-sialylation using 4-O-4-nitropicoloylated ethyl thiosialoside as glycosyl
donor has been disclosed. This method is a general protocol for the -selective and facile assembly of diverse
sialoside derivatives which not only include a range of natural structures, such as (2,3)/(2,6)-linked Neu5Ac-Gal,
(2,6)-linked Neu5Ac-GalNAc disaccharide, and (2,8)/(2,9)-linked disialosides frameworks, but also include
various non-natural sialic linkages. Employment of the method allowed the stereoselective generation of the
protected trisaccharide fragment 11 derived from the serotype Ia GBS CPS.
Experimental section
General methods
All non-aqueous reactions were performed under a nitrogen atmosphere and monitored by thin layer chromatography
(TLC) using Silica Gel GF254 plates with detection by charring with 10% (v/v) H2SO4 in EtOH or by UV detection.
Solvents used in the reactions were distilled from appropriate drying agents prior to use. Silica gel (200-300 mesh)
was used for column chromatography. Optical rotations were measured at 25 ± 0.3 °C for solutions in a 0.5 dm cell.
High resolution mass spectra (HRMS) were acquired in the ESI mode. 1H and 13C NMR spectra were recorded on a
400 MHz or 600 MHz spectrometer in CDCl3 with tetramethylsilane (TMS) as internal reference. Chemical shifts
are expressed in ppm downfield from the internal TMS absorption. Standard splitting patterns are abbreviated: s
1
(singlet), d (doublet), t (triplet), m (multiplet). J values are given in Hz. The / ratio was determined by H NMR
analysis.
General Glycosylation Procedure with NIS/TfOH as Promoter: A mixture of sialyl donor (1.5 or 2.0 equiv),
glycosyl acceptor (1.0 equiv) and freshly activated 4 Å molecular sieves in CH2Cl2 or CH2Cl2/CH3CN (1:1, v/v)
co-solvent (100 mM) was stirred under nitrogen for 0.5-1 h at room temperature. The reaction was cooled to -78 °C,
then NIS (1.5 equiv) and TfOH (0.1 equiv) were added. The reaction mixture was gradually warmed to -30 °C. The
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reaction was monitored by TLC until disappearance of the acceptor or the donor. Then the reaction was quenched
with triethylamine, diluted with CH2Cl2 and filtered. The filtrate was concentrated in vacuo. The resulting residue
was purified by silica gel column chromatography to afford the sialoside product.
p-Methoxyphenyl 2,6-di-O-benzyl-3-O-[methyl 5-(2,2,2-trichloroethoxycarbonylamino)-7,8,9-tri-O-acetyl-3,5-
dideoxy-4-O-picoloyl-D-glycero-D-galacto-2-nonulopyranoylonate-β-D-galactopyranoside
(3a);
Methyl
5-(2,2,2-trichloroethoxycarbonylamino)-7,8,9-tri-O-acetyl-4-O-picoloyl-2,6-anhydro-3,5-dideoxy-D-glycero-D-
galacto-non-2-enonate (4a)
Protocol a: The disaccharide 3a and glycal ester 4a were obtained by the glycosylation of donor 1a (68 mg, 0.09
mmol) with galactosyl acceptor 2[11] (21 mg, 0.045 mmol) using general glycosylation procedure in CH2Cl2 (0.9 mL)
with NIS (30 mg, 0.135 mmol)/TfOH (0.8 L, 9 μmol) as promoter. The resulting residue was purified by silica gel
column chromatography (2:1→3:2, petroleum ether-EtOAc) to afford 3a (10 mg,  = 2:1, 19.5%) and 4a as white
solids (54 mg, 87%).
Protocol b: The disaccharide 3a and glycal ester 4a were obtained by the glycosylation of donor 1a (68 mg, 0.09
mmol) with galactosyl acceptor 2 (21 mg, 0.045 mmol) using general glycosylation procedure in CH2Cl2/CH3CN 1:1
(0.9 mL) with NIS (30 mg, 0.135 mmol)/TfOH (0.8 L, 9 μmol) as promoter. The resulting residue was purified by
silica gel column chromatography (2:1→3:2, petroleum ether-EtOAc) to afford 3a (21 mg,  = 6:1, 40%) and 4a
(39 mg, 63%) as white solids;
-3a: Rf = 0.2 (2:1, petroleum ether-EtOAc); []25D +40.00 (c 0.10, CHCl3);-3a: 1H NMR (400 MHz, CDCl3) δ
8.78 (d, J = 4.7 Hz, 1H), 8.05 (d, J = 7.7 Hz, 1H), 7.85 (t, J = 7.7 Hz, 1H), 7.51 (d, J = 12.0 Hz, 1H), 7.42-7.15 (m,
10H), 7.02 (d, J = 9.0 Hz, 2H), 6.79 (d, J = 9.0 Hz, 2H), 5.48-5.38 (m, 3H), 5.05 (d, J = 9.6 Hz, 1H), 4.94 (d, J = 7.7
Hz, 1H), 4.89 (d, J = 11.6 Hz, 1H), 4.83 (d, J = 11.9 Hz, 1H), 4.79 (d, J = 11.9 Hz, 1H), 4.58 (s, 2H), 4.38 (d, J =
12.1 Hz, 1H), 4.32-4.23 (m, 3H), 4.03 (dd, J = 12.6, 4.9 Hz, 1H), 3.88-3.85 (m, 4H), 3.84-3.78 (m, 4H), 3.77-3.75
(m, 4H), 2.83 (dd, J = 12.7, 4.8 Hz, 1H), 2.14-2.12 (m, 4H), 2.02 (s, 3H), 1.95 (s, 3H); 13C NMR (150 MHz, CDCl3)
δ 170.81, 170.20, 170.14, 168.50, 164.08, 155.31, 154.18, 151.77, 150.04, 138.98, 138.28, 128.52, 128.29, 127.97,
127.83, 127.78, 127.51, 125.81, 118.66, 118.47, 114.88, 114.58, 102.86, 98.13, 95.36, 76.06, 75.17, 74.40, 73.78,
73.24, 72.02, 69.97, 69.55, 68.41, 68.37, 67.50, 62.34, 55.79, 53.35, 51.54, 37.17, 21.31, 20.92, 20.80; HRMS (ESI):
m/z calcd for C52H57Cl3N2O20 [M+Na]+: 1157.2462, found: 1157.2460. 4a: Rf = 0.3 (2:1, petroleum ether-EtOAc);
1
[]25D +78.00 (c 0.10, CHCl3); H NMR (400 MHz, CDCl3)  8.80 (d, J = 4.7 Hz, 1H), 8.14 (d, J = 7.8 Hz, 1H), 7.90
(t, J = 7.8 Hz, 1H), 7.57-7.54 (m, 1H), 6.19 (dd, J = 8.7, 2.7 Hz, 1H), 6.12 (d, J = 2.6 Hz, 1H), 5.77-5.74 (m, 1H),
5.57 (dd, J = 6.3, 1.9 Hz, 1H), 5.43-5.39 (m, 1H), 4.90 (d, J = 12.0 Hz, 1H), 4.67 (d, J = 10.6 Hz, 1H), 4.60 (dd, J =
12.5, 2.7 Hz, 1H), 4.44 (d, J = 12.0 Hz, 1H), 4.24 (dd, J = 12.5, 5.9 Hz, 1H), 4.18-4.11 (m, 1H), 3.81 (s, 3H), 2.17 (s,
3H), 2.07 (s, 3H), 2.06 (s, 3H); 13C NMR (150 MHz, CDCl3) δ 170.82, 170.36, 170.07, 163.72, 161.64, 154.26,
149.22, 145.99, 138.87, 128.02, 126.17, 107.63, 95.47, 75.75, 74.43, 70.43, 70.24, 67.64, 62.07, 52.76, 49.36, 21.05,
20.98, 20.93; HRMS (ESI): m/z calcd for C25H27Cl3N2O13 [M+Na]+: 691.0471, found: 691.0475.
p-Methoxyphenyl 2,6-di-O-benzyl-3-O-[methyl 5-(2,2,2-trichloroethoxycarbonylamino)-7,8,9-tri-O-acetyl-3,5-
dideoxy-4-O-(4-nitropicoloyl)-D-glycero-D-galacto-2-nonulopyranoylonate]-β-D-galactopyranoside
Methyl 5-(2,2,2-trichloroethoxycarbonylamino)-7,8,9-tri-O-acetyl-4-O-(4-nitropicoloyl)-2,6-anhydro-3,5-
dideoxy-D-glycero-D-galacto-non-2-enonate (4b)
(3b);
The disaccharide 3b and glycal ester 4b were obtained by the glycosylation of donor 1b (83 mg, 0.11 mmol) with
galactosyl acceptor 2 (25 mg, 0.055 mmol) using general glycosylation procedure in CH2Cl2/CH3CN 1:1 (1.1 mL)
with NIS (37 mg, 0.165 mmol)/TfOH (0.97 L, 11.0 mol) as promoter. The resulting residue was purified by silica
gel column chromatography (3:1→2:1, petroleum ether-EtOAc) to afford 3b (36 mg,  = 15:1, 56%) and 4b (35
mg, 46%) as white solids.
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-3b: Rf = 0.2 (2:1, petroleum ether-EtOAc); []25D +17.27 (c 0.22, CHCl3); -3b: 1H NMR (400 MHz, CDCl3)
 9.07 (d, J = 5.2 Hz, 1H), 8.71 (d, J = 2.1 Hz, 1H), 8.23 (dd, J = 5.2, 2.2 Hz, 1H), 7.40-7.14 (m, 10H), 7.03 (d, J =
9.0 Hz, 2H), 6.79 (d, J = 9.0 Hz, 2H), 5.49-5.40 (m, 3H), 5.03 (d, J = 9.4 Hz, 1H), 4.96-4.89 (m, 2H), 4.86-4.78 (m,
2H), 4.58 (s, 2H), 4.39 (d, J = 12.1 Hz, 1H), 4.34-4.23 (m, 3H), 4.04 (dd, J = 12.6, 4.8 Hz, 1H), 3.88-3.87 (m, 4H),
3.87-3.78 (m, 4H), 3.78-3.75 (m, 4H), 2.83 (dd, J = 12.9, 4.7 Hz, 1H), 2.18 (t, J = 12.4 Hz, 1H), 2.12 (s, 3H), 2.02 (s,
3H), 1.96 (s, 3H); 13C NMR (150 MHz, CDCl3)  170.78, 170.27, 170.13, 168.42, 162.60, 155.35, 154.77, 154.12,
152.49, 151.74, 150.14, 138.99, 138.25, 128.57, 128.52, 128.42, 128.28, 127.98, 127.85, 127.78, 127.51, 119.75,
118.68, 118.38, 114.59, 102.92, 98.07, 95.38, 76.08, 75.20, 74.48, 73.79, 73.22, 71.92, 71.05, 69.50, 68.43, 67.49,
62.26, 55.78, 53.42, 51.54, 37.02, 21.29, 20.91, 20.79; HRMS (ESI): m/z calcd for C52H56Cl3N3O22 [M+Na]+:
1202.2313, found: 1202.2319. 4b: Rf = 0.25 (2:1, petroleum ether-EtOAc); []25D +79.09 (c 0.22, CHCl3); 1H NMR
(400 MHz, CDCl3)  9.08 (d, J = 5.2 Hz, 1H), 8.77 (d, J = 1.9 Hz, 1H), 8.23 (dd, J = 5.2, 2.1 Hz, 1H), 6.23 (dd, J =
8.5, 2.7 Hz, 1H), 6.11 (d, J = 2.7 Hz, 1H), 5.73 (d, J = 9.0 Hz, 1H), 5.56 (dd, J = 5.9, 1.8 Hz, 1H), 5.42-5.38 (m, J =
6.0, 2.7 Hz, 1H), 4.90 (d, J = 12.1 Hz, 1H), 4.68-4.57 (m, 2H), 4.43 (d, J = 12.1 Hz, 1H), 4.25 (dd, J = 12.5, 6.0 Hz,
1H), 4.17-4.10 (m, 1H), 3.82 (s, 3H), 2.16 (s, 3H), 2.07 (s, 3H), 2.06 (s, 3H); 13C NMR (100 MHz, CDCl3)  170.84,
170.49, 170.23, 163.09, 161.50, 154.82, 154.19, 152.56, 150.13, 146.10, 119.85, 118.46, 107.18, 95.40, 75.79, 74.52,
70.64, 70.61, 67.63, 62.01, 52.86, 49.32, 21.05, 20.95, 20.92; HRMS (ESI): m/z calcd for C25H26Cl3N3O15 [M+Na]+:
736.0322, found: 736.0325.
p-Methoxyphenyl 2,6-di-O-benzyl-3-O-[methyl 5-(2,2,2-trichloroethoxycarbonylamino)-7,8,9-tri-O-acetyl-3,5-
dideoxy-4-O-benzoyl-D-glycero-D-galacto-2-nonulopyranoylonate]-β-D-galactopyranoside
(3c);
Methyl
5-(2,2,2-trichloroethoxycarbonylamino)-7,8,9-tri-O-acetyl-4-O-benzoyl-2,6-anhydro-3,5-dideoxy-D-glycero-D-
galacto-non-2-enonate (4c)
The disaccharide 3c and glycal ester 4c were obtained by the glycosylation of donor 1c (62 mg, 0.085 mmol) with
galactosyl acceptor 2 (20 mg, 0.043 mmol) using general glycosylation procedure in CH2Cl2/CH3CN 1:1 (0.85 mL)
with NIS (29 mg, 0.128 mmol)/TfOH (0.75 L, 8.5 mol) as promoter. The resulting residue was purified by silica
gel column chromatography (4:1→3:1, petroleum ether-EtOAc) to afford 3c (32 mg,  = 5:1, 65%) and 4c (23 mg,
40%) as a white solid.
-3c: Rf = 0.4 (2:1, petroleum ether-EtOAc); []25D +19.69 (c 0.32, CHCl3); -3c: 1H NMR (400 MHz, CCCl3) δ
7.96 (d, J = 7.3 Hz, 2H), 7.57 (t, J = 7.4 Hz, 1H), 7.46-7.37 (m, 4H), 7.34-7.24 (m, 7H), 7.22-7.15 (m, 1H), 7.05 (d, J
= 9.0 Hz, 2H), 6.80 (d, J = 9.1 Hz, 2H), 5.48-5.42 (m, 2H), 5.18-5.11 (m, 1H), 4.98-4.88 (m, 3H), 4.82 (d, J = 8.9 Hz,
1H), 4.79 (d, J = 9.3 Hz, 1H), 4.58 (s, 2H), 4.35 (d, J = 12.1 Hz, 1H), 4.33-4.24 (m, 2H), 4.17 (dd, J = 10.8, 1.7 Hz,
1H), 4.01 (dd, J = 12.6, 4.4 Hz, 1H), 3.96-3.89 (m, 1H), 3.88-3.84 (m, 5H), 3.83-3.75 (m, 6H), 2.78 (dd, J = 13.1, 4.8
Hz, 1H), 2.12 (s, 3H), 2.08-2.01 (m, 4H), 2.00 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 170.82, 170.20, 170.02,
168.69, 166.08, 155.32, 154.38, 151.74, 138.89, 138.29, 133.75, 130.02, 129.11, 128.59, 128.50, 128.33, 128.08,
127.81, 127.76, 127.63, 118.66, 114.58, 102.96, 98.08, 95.19, 75.77, 75.24, 74.49, 73.76, 73.71, 73.28, 72.67, 69.61,
69.53, 68.52, 68.40, 67.47, 62.40, 55.77, 53.34, 51.49, 37.30, 21.30, 20.92, 20.79; HRMS (ESI): m/z calcd for
C53H58Cl3NO20 [M+Na]+: 1156.2510, found: 1156.2517. 4c: Rf = 0.5 (2:1, petroleum ether-EtOAc); []25D +84.38 (c
0.32, CHCl3); 1H NMR (400 MHz, CDCl3) δ 8.00 (dd, J = 8.2, 1.4 Hz, 2H), 7.61-7.54 (m, 1H), 7.42 (t, J = 7.8 Hz,
2H), 6.11 (d, J = 2.7 Hz, 1H), 5.91 (dd, J = 8.7, 2.7 Hz, 1H), 5.59 (dd, J = 5.6, 2.3 Hz, 1H), 5.44 (d, J = 9.7 Hz, 1H),
5.38-5.35 (m, 1H), 4.89 (d, J = 12.1 Hz, 1H), 4.65 (dd, J = 12.5, 2.8 Hz, 1H), 4.50 (dd, J = 10.5, 2.4 Hz, 1H), 4.41 (d,
J = 12.1 Hz, 1H), 4.28-4.18 (m, 2H), 3.81 (s, 3H), 2.16 (s, 3H), 2.07 (s, 3H), 2.06 (s, 3H); 13C NMR (150 MHz,
CDCl3) δ 170.85, 170.33, 170.26, 166.37, 161.65, 154.30, 145.46, 133.78, 130.03, 129.15, 128.65, 108.37, 95.29,
76.54, 74.58, 71.00, 69.39, 67.67, 62.09, 52.77, 49.14, 21.04, 20.93, 20.90; HRMS (ESI): m/z calcd for
C26H28Cl3NO13 [M+Na]+: 690.0518, found:690.0523.
8
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201901587
European Journal of Organic Chemistry
p-Methoxyphenyl 3,4-O-isopropylidene-6-O-[methyl 5-(2,2,2-trichloroethoxycarbonylamino)-7,8,9-tri-O-acetyl
-3,5-dideoxy-4-O-(4-nitropicoloyl)-D-glycero--D-galacto-2-nonulopyranoylonate]--D-galactopyranoside (6a)
The disaccharide 6a and glycal ester 4b were obtained by the glycosylation of donor 1b (37 mg, 0.05 mmol) with
acceptor 5a[14] (11 mg, 0.033 mmol) using general glycosylation procedure in CH2Cl2/CH3CN (1:1) (0.5 mL) with
NIS (17 mg, 0.075 mmol)/TfOH (0.44 L, 5 mol) as promoter. The resulting residue was purified by silica gel
column chromatography (2:1→1:1, petroleum ether-EtOAc) to afford 6a (32 mg,  only, 91%) and 4b (4 mg, 12%)
1
as white solids. 6a: Rf = 0.25 (1:1, petroleum ether-EtOAc); []25 -2.89 (c 0.30, CHCl3); H NMR (400 MHz,
D
CDCl3)  9.05 (d, J = 5.3 Hz, 1H), 8.71 (d, J = 2.1 Hz, 1H), 8.21 (dd, J = 5.2, 2.2 Hz, 1H), 7.03 (d, J = 9.1 Hz, 2H),
6.77 (d, J = 9.1 Hz, 2H), 5.58-5.52 (m, 1H), 5.44-5.36 (m, 2H), 5.20 (d, J = 9.1 Hz, 1H), 4.85 (d, J = 12.1 Hz, 1H),
4.71 (d, J = 8.1 Hz, 1H), 4.42-4.32 (m, 3H), 4.25 (dd, J = 5.5, 2.1 Hz, 1H), 4.22-4.12 (m, 2H), 4.10-4.06 (m, 1H),
4.00 (dd, J = 10.4, 6.8 Hz, 1H), 3.86 (s, 3H), 3.84-3.76 (m, 3H), 3.74 (s, 3H), 2.85 (dd, J = 12.9, 4.9 Hz, 1H),
2.18-2.12 (m, 7H), 1.99 (s, 3H), 1.56 (s, 3H) 1.38 (s, 3H); 13C NMR (150 MHz, CDCl3)  170.96, 170.53, 169.96,
167.93, 162.72, 155.50, 154.74, 154.09, 152.47, 151.28, 150.20, 119.73, 118.61, 118.37, 114.56, 110.52, 101.68,
98.97, 95.45, 78.70, 74.41, 73.62, 73.20, 71.78, 71.63, 70.77, 68.56, 67.65, 63.83, 62.36, 55.74, 53.20, 51.79, 37.70,
28.27, 26.47, 21.16, 20.99, 20.88; HRMS (ESI): m/z calcd for C41H48Cl3N3O22 [M+Na]+: 1062.1687, found:
1062.1699.
Methyl 2,3,4-tri-O-benzyl-6-O-[methyl 5-(2,2,2-trichloroethoxycarbonylamino)-7,8,9-tri-O-acetyl-3,5-dideoxy-
4-O-(4-nitropicoloyl)-D-glycero--D-galacto-2-nonulopyranoylonate]--D-glucopyranoside (6b)
The disaccharide 6b and glycal ester 4b were obtained by the glycosylation of donor 1b (50 mg, 0.064 mmol) with
acceptor 5b[15] (20 mg, 0.043 mmol) using general glycosylation procedure in CH2Cl2/CH3CN (1:1) (0.64 mL) with
NIS (22 mg, 0.08 mmol)/TfOH (0.57 L, 6.4 mol) as promoter. The resulting residue was purified by silica gel
column chromatography (2:1→3:2, petroleum ether-EtOAc) to afford 6b (45 mg,  only, 89%) and 4b (6.5 mg, 14%)
1
as white solids. 6b: Rf = 0.2 (1:1, petroleum ether-EtOAc); []25 +37.14 (c 0.14, CHCl3); H NMR (400 MHz,
D
CDCl3)  9.06 (d, J = 5.2 Hz, 1H), 8.73 (d, J = 2.1 Hz, 1H), 8.21 (dd, J = 5.2, 2.2 Hz, 1H), 7.43-7.13 (m, 15H),
5.56-5.44 (m, 1H), 5.36 (s, 2H), 5.08 (d, J = 9.1 Hz, 1H), 4.95-4.85 (m, 2H), 4.82 (d, J = 13.0 Hz, 2H), 4.76 (d, J =
10.9 Hz, 2H), 4.65 (d, J = 12.2 Hz, 1H), 4.61 (d, J = 3.5 Hz, 1H), 4.37-4.34 (m, 2H), 4.25 (dd, J = 10.7, 3.8 Hz, 1H),
4.05 (d, J = 12.7 Hz, 1H), 3.95 (t, J = 9.3 Hz, 1H), 3.85-3.74 (m, 5H), 3.71-3.64 (m, 1H), 3.61 (t, J = 9.4 Hz, 1H),
3.52-3.47 (m, 2H), 3.36 (s, 3H), 2.95 (dd, J = 12.7, 4.8 Hz, 1H), 2.14-2.09 (m, 4H), 2.02 (s, 3H), 1.83 (s, 3H); 13C
NMR (100 MHz, CDCl3)  170.70, 170.32, 169.87, 167.79, 162.67, 154.82, 154.02, 152.48, 150.27, 139.01, 138.79,
138.39, 128.56, 128.52, 128.46, 128.24, 128.05, 128.00, 127.94, 127.88, 127.66, 119.69, 118.37, 98.69, 98.42, 95.48,
82.15, 79.67, 75.90, 74.95, 74.44, 73.50, 71.28, 70.90, 69.63, 67.66, 67.18, 63.69, 61.79, 55.33, 53.06, 51.85, 38.43,
21.20, 20.86, 20.65; HRMS (ESI): m/z calcd for C53H58Cl3N3O21 [M+Na]+: 1200.2520, found: 1200.2529.
Methyl 2,3-di-O-benzyl-5-O-[methyl 5-(2,2,2-trichloroethoxycarbonylamino)-7,8,9-tri-O-acetyl-3,5-dideoxy-
4-O-(4-nitropicoloyl)-D-glycero-D-galacto-2-nonulopyranoylonate]--D-arabinofuranoside (6c)
The disaccharide 6c and glycal ester 4b were obtained by the glycosylation of donor 1b (47 mg, 0.053 mmol) with
acceptor 5c[16] (11 mg, 0.035 mmol) using general glycosylation procedure in CH2Cl2/CH3CN (1:1) (0.53 mL) with
NIS (18 mg, 0.08 mmol)/TfOH (0.47 L, 5.3 mol) as promoter. The resulting residue was purified by silica gel
column chromatography (3:1→2:1, petroleum ether-EtOAc) to afford 6c (28 mg,  = 15:1, 83%) and 4b (9 mg,
1
21%) as white solids. -6c: Rf = 0.4 (1:1, petroleum ether-EtOAc); []25 +33.33 (c 0.24, CHCl3); H NMR (400
D
MHz, CDCl3)  9.00 (d, J = 5.1 Hz, 1H), 8.67 (d, J = 2.1 Hz, 1H), 8.15 (dd, J = 5.2, 2.2 Hz, 1H), 7.35-7.20 (m, 10H),
5.49-5.40 (m, 1H), 5.39-5.29 (m, 2H), 5.04 (dd, J = 10.3, 4.6 Hz, 1H), 4.84 (d, J = 1.3 Hz, 1H), 4.79 (d, J = 12.1 Hz,
1H), 4.58 (d, J = 12.0 Hz, 1H), 4.50 (d, J = 11.9 Hz, 1H), 4.46 (d, J = 11.8 Hz, 1H), 4.40 (d, J = 11.8 Hz, 1H),
4.35-4.23 (m, 2H), 4.12-4.06 (m, 2H), 4.01-3.93 (m, 3H), 3.91 (dd, J = 3.3, 1.3 Hz, 1H), 3.77-3.68 (m, 4H), 3.52 (dd,
J = 10.9, 3.8 Hz, 1H), 3.29 (s, 3H), 2.83 (dd, J = 12.7, 4.8 Hz, 1H), 2.11-2.08 (m, 4H), 1.99 (s, 3H), 1.95 (s, 3H); 13C
9
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201901587
European Journal of Organic Chemistry
NMR (100 MHz, CDCl3)  170.73, 170.37, 169.90, 167.96, 162.69, 154.82, 154.09, 152.49, 150.30, 138.20, 137.78,
128.54, 128.54, 127.97, 127.89, 127.80, 119.68, 118.36, 107.40, 98.61, 95.48, 88.50, 83.56, 80.22, 74.48, 72.51,
72.12, 71.45, 71.02, 68.12, 67.44, 64.24, 61.95, 55.09, 53.01, 51.88, 38.13, 21.18, 20.91, 20.86; HRMS (ESI): m/z
calcd for C45H50Cl3N3O20 [M+Na]+: 1080.1945, found: 1080.1951.
Methyl [N-benzylbenzyloxycarbonyl-5-amino-pentanyl 5-(2,2,2-trichloroethoxycarbonylamino)-7,8,9-tri-
O-acetyl-3,5-dideoxy-4-O-(4-nitropicoloyl)-D-glycero--D-galacto-non-2-ulopyranosid]onate (6d)
The compound 6d and glycal ester 4b were obtained by the glycosylation of donor 1b (41 mg, 0.053 mmol) with
acceptor 5d[17] (11 mg, 0.035 mmol) using general glycosylation procedure in CH2Cl2/CH3CN (1:1) (0.53 mL) with
NIS (18 mg, 0.08 mmol)/TfOH (0.47 L, 5.3 mol) as promoter. The resulting residue was purified by silica gel
column chromatography (3:1→2:1, petroleum ether-EtOAc) to afford 6d (29 mg,  only, 82%) and 4b (9 mg, 24%)
1
as white solids. 6d: Rf = 0.4 (1:1, petroleum ether-EtOAc); []25 +17.86 (c 0.28, CHCl3); H NMR (400 MHz,
D
CDCl3)  9.02 (d, J = 5.2 Hz, 1H), 8.70 (d, J = 2.1 Hz, 1H), 8.17 (dd, J = 5.3, 2.2 Hz, 1H), 7.42-7.09 (m, 10H),
5.46-5.34 (m, 3H), 5.15-5.09 (m, 3H), 4.81 (d, J = 12.1 Hz, 1H), 4.46 (d, J = 6.4 Hz, 2H), 4.35 (d, J = 12.3 Hz, 1H)
4.30-4.24 (m, 2H), 4.20-4.10 (m, 1H), 3.79 (s, 3H), 3.76-3.71 (m, 2H), 3.27-3.11 (m, 3H), 2.80 (dd, J = 12.7, 4.7 Hz,
1H), 2.12 (s, 6H), 2.09-2.00 (m, 4H), 1.54-1.52 (m, 4H), 1.33-1.20 (m, 2H); 13C NMR (100 MHz, CDCl3)  170.80,
170.46, 170.02, 168.34, 162.73, 154.81, 154.11, 152.48, 150.32, 138.08, 137.03, 128.68, 128.59, 128.05, 127.97,
127.42, 119.67, 118.35, 98.73, 95.48, 74.48, 71.47, 71.16, 68.34, 67.59, 67.31, 65.07, 62.21, 52.93, 51.87, 38.30,
29.43, 23.37, 21.19, 21.01, 20.89; HRMS (ESI): m/z calcd for C45H51Cl3N4O18 [M+Na]+: 1063.2156, found:
1063.2157.
p-Methoxyphenyl 3,4-O-isopropylidene-2-deoxy-2-acetamido-6-O-[methyl 5-(2,2,2-trichloroethoxycarbonyl-
amino)-7,8,9-tri-O-acetyl-3,5-dideoxy-4-O-(4-nitropicoloyl)-D-glycero--D-galacto-2-nonulopyranoylonate]--
D-galactopyranoside (6e)
The disaccharide 6e and glycal ester 4b were obtained by the glycosylation of donor 1b (56 mg, 0.07 mmol) with
acceptor 5e (18 mg, 0.047 mmol) using general glycosylation procedure in CH2Cl2/CH3CN (1:1) (0.5 mL) with NIS
(24 mg, 0.108 mmol)/TfOH (0.64 L, 7 mol) as promoter. The resulting residue was purified by silica gel column
chromatography (2:1→1:1, petroleum ether-EtOAc) to afford 6e (16 mg,  only, 30%) and 4b (37 mg, 72%) as
white solids. 6e: Rf = 0.2 (3:2, petroleum ether-EtOAc); []25D +18.75 (c 0.16, CHCl3); 1H NMR (400 MHz, CDCl3)
 9.06 (d, J = 5.2 Hz, 1H), 8.73 (d, J = 2.1 Hz, 1H), 8.22 (dd, J = 5.2, 2.1 Hz, 1H), 7.06 (d, J = 9.1 Hz, 2H), 6.79 (d,
J = 9.1 Hz, 2H), 5.90 (d, J = 9.1 Hz, 1H), 5.75-5.70 (m, 1H), 5.38-5.30 (m, 2H), 5.03 (d, J = 9.5 Hz, 1H), 4.93 (d, J =
8.3 Hz, 1H), 4.76 (d, J = 12.1 Hz, 1H), 4.51-4.43 (m, 1H), 4.41 (d, J = 12.1 Hz, 1H), 4.31 (dd, J = 12.2, 2.3 Hz, 1H),
4.23 (dd, J = 11.0, 3.3 Hz, 1H), 4.08-4.06 (m, 1H), 4.03 (t, J = 2.9 Hz, 1H), 4.00-3.95 (m, 1H), 3.95-3.89 (m, 3H),
3.89 (s, 3H), 3.75 (s, 3H), 3.68 (d, J = 3.3 Hz, 1H), 3.00 (dd, J = 12.5, 4.5 Hz, 1H), 2.22-2.12 (m, 10H), 1.78 (s, 3H),
1.48 (s, 3H), 1.37 (s, 3H); 13C NMR (100 MHz, CDCl3)  171.73, 170.85, 170.50, 170.40, 168.46, 162.84, 155.40,
154.86, 154.17, 152.55, 152.17, 150.05, 119.83, 119.21, 118.39, 114.45, 101.27, 99.02, 97.27, 95.30, 74.59, 72.72,
71.51, 71.18, 67.59, 66.79, 66.54, 66.35, 63.98, 63.01, 55.82, 53.23, 51.32, 50.20, 38.11, 29.12, 23.75, 21.52, 21.08,
20.67, 18.97; HRMS (ESI): m/z calcd for C43H51Cl3N4O22 [M+Na]+: 1103.1953, found: 1103.1952.
p-Methoxyphenyl 3,4-O-isopropylidene-2-deoxy-2-phthalimido-6-O-[methyl 5-(2,2,2-trichloroethoxycarbonyl-
amino)-7,8,9-tri-O-acetyl-3,5-dideoxy-4-O-(4-nitropicoloyl)-D-glycero--D-galacto-2-nonulopyranoylonate]--
D-galactopyranoside (6f)
The disaccharide 6f and glycal ester 4b were obtained by the glycosylation of donor 1b (38 mg, 0.05 mmol) with
acceptor 5f (15 mg, 0.033 mmol) using general glycosylation procedure in CH2Cl2/CH3CN (1:1) (0.5 mL) with NIS
(17 mg, 0.075 mmol)/TfOH (0.44 L, 5 mol) as promoter. The resulting residue was purified by silica gel column
chromatography (2:1→1:1, petroleum ether-EtOAc) to afford 6f (31 mg,  only, 81%) and 4b (8 mg, 23%) as white
10
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201901587
European Journal of Organic Chemistry
1
solids. 6f: Rf = 0.25 (1:1, petroleum ether-EtOAc); []25 +37.33 (c 0.20, CHCl3); H NMR (400 MHz, CDCl3) 
D
9.06 (d, J = 5.3 Hz, 1H), 8.73 (d, J = 2.2 Hz, 1H), 8.22 (dd, J = 5.2, 2.2 Hz, 1H), 7.85-7.83 (m, 2H), 7.74-7.71 (m,
2H), 6.86 (d, J = 9.1 Hz, 2H), 6.67 (d, J = 9.1 Hz, 2H), 5.68-5.53 (m, 2H), 5.48-5.38 (m, 2H), 5.15 (d, J = 8.9 Hz,
1H), 4.92-4.80 (m, 2H), 4.50 (t, J = 8.9 Hz, 1H), 4.42-4.35 (m, 2H), 4.30 (dd, J = 5.1, 2.0 Hz, 1H), 4.27-4.19 (m, 2H),
4.15-4.07 (m, 1H), 3.90-3.86 (m, 4H), 3.83-3.71 (m, 2H), 3.69 (s, 3H), 2.86 (dd, J = 13.1, 5.0 Hz, 1H), 2.19 (s, 3H),
2.15 (s, 3H), 2.07-2.04 (m, 4H), 1.68 (s, 3H), 1.36 (s, 3H); 13C NMR (100 MHz, CDCl3)  170.79, 170.62, 169.88,
168.00, 162.75, 155.60, 154.81, 154.07, 152.47, 150.98, 150.36, 134.27, 131.99, 123.63, 119.68, 119.00, 118.37,
114.49, 110.82, 98.77, 97.83, 95.52, 74.45, 74.23, 73.17, 72.02, 71.49, 70.76, 68.78, 67.69, 65.71, 63.70, 62.14,
55.71, 55.08, 53.55, 53.18, 51.93, 37.68, 28.13, 26.63, 21.15, 21.04, 20.88; HRMS (ESI): m/z calcd for
C49H51Cl3N4O23 [M+Na]+: 1191.1902, found: 1191.1902.
Methyl (methyl 5-amino-5-N,4-O-carbonyl-3,5-dideoxy-9-O-[methyl 5-(2,2,2-trichloroethoxycarbonylamino)-
7,8,9-tri-O-acetyl-3,5-dideoxy-4-O-(4-nitropicoloyl)-D-glycero--D-galacto-2-nonulopyranoylonate]-D-glycero
--D-galacto-2-nonulopyranosid)onate (6h)
The disaccharide 6h and glycal ester 4b were obtained by the glycosylation of donor 1b (41 mg, 0.053 mmol) with
acceptor 5h (11 mg, 0.035 mmol) using general glycosylation procedure in CH2Cl2/CH3CN (1:1) (0.53 mL) with
NIS (18 mg, 0.08 mmol)/TfOH (0.47 L, 5.3 mol) as promoter. The resulting residue was purified by silica gel
column chromatography (1:1→1:3, petroleum ether-EtOAc) to afford 6h (32 mg,  only, 90%) and 4b (5 mg, 13%)
1
as white solids. 6h: Rf = 0.5 (10:1, CH2Cl2-MeOH); []25 +6.50 (c 0.62, CHCl3); H NMR (400 MHz, CDCl3) 
D
9.08 (d, J = 5.2 Hz, 1H), 8.73 (d, J = 2.1 Hz, 1H), 8.23 (dd, J = 5.3, 2.2 Hz, 1H), 6.29 (s, 1H), 5.58-5.44 (m, 2H),
5.41 (s, 2H), 4.81 (d, J = 12.2 Hz, 1H), 4.58-4.49 (m, 1H), 4.47-4.29 (m, 3H), 4.15-4.00 (m, 3H), 3.92-3.73 (m, 10H),
3.54 (t, J = 10.5 Hz, 1H), 3.31 (s, 3H), 2.87 (dd, J = 13.1, 5.0 Hz, 1H), 2.61 (dd, J = 11.9, 4.1 Hz, 1H), 2.26-2.18 (m,
1H), 2.16 (s, 3H), 2.13 (s, 3H), 2.08-2.03 (m, 4H); 13C NMR (150 MHz, CDCl3)  171.15, 170.36, 170.27, 168.15,
167.96, 162.76, 160.18, 154.79, 154.28, 152.60, 150.07, 119.88, 118.38, 99.48, 98.51, 95.41, 77.30, 74.98, 74.45,
71.72, 71.12, 70.96, 69.34, 68.54, 67.46, 66.47, 62.55, 57.95, 53.40, 53.14, 51.71, 51.51, 37.47, 37.14, 21.19, 20.91;
HRMS (ESI): m/z calcd for C37H45Cl3N4O24 [M+Na]+: 1057.1381, found: 1057.1393.
p-Methoxyphenyl 2,6-di-O-(2-naphthylmethyl)-3-O-[methyl 5-(2,2,2-trichloroethoxycarbonylamino)-7,8,9-
tri-O-acetyl-3,5-dideoxy-4-O-(4-nitropicoloyl)-D-glycero--D-galacto-2-nonulopyranoylonate]--D-galactopyr
anoside (6i)
The disaccharide 6i and glycal ester 4b were obtained by the glycosylation of donor 1b (228 mg, 0.29 mmol) with
galactosyl acceptor 5i (82 mg, 0.145 mmol) using general glycosylation procedure in CH2Cl2/CH3CN (1:1) (2.9 mL)
with NIS (98 mg, 0.435 mmol)/TfOH (2.60 L, 29 mol) as promoter. The resulting residue was purified by silica
gel column chromatography (2:1→1:1, petroleum ether-EtOAc) to afford 6i (97 mg,  only, 52%) and 4b (134 mg,
64%) as white solids. 6i: Rf = 0.35 (1:1, petroleum ether-EtOAc); []25D +15.00 (c 0.24, CHCl3); 1H NMR (400 MHz,
CDCl3)  8.99 (d, J = 5.2 Hz, 1H), 8.55 (d, J = 2.1 Hz, 1H), 8.17 (dd, J = 5.2, 2.2 Hz, 1H), 7.88-7.64 (m, 8H),
7.56-7.40 (m, 4H), 7.37-7.28 (m, 2H), 7.07 (d, J = 9.0 Hz, 2H), 6.78 (d, J = 9.0 Hz, 2H), 5.51-5.34 (m, 3H), 5.07 (d,
J = 11.6 Hz, 1H), 5.04-5.00 (m, 2H), 4.96 (d, J = 11.6 Hz, 1H), 4.79 (d, J = 12.1 Hz, 1H), 4.75 (s, 2H), 4.37 (d, J =
12.1 Hz, 1H), 4.32 (dd, J = 12.6, 2.5 Hz, 1H), 4.31-4.25 (m, 2H), 4.02 (dd, J = 12.6, 5.2 Hz, 1H), 3.95-3.87 (m, 3H),
3.86(s, 3H), 3.84-3.79 (m, 2H), 3.73 (s, 3H), 3.66 (d, J = 13.1 Hz, 1H), 2.83 (dd, J = 12.9, 4.8 Hz, 1H), 2.21 (t, J =
12.4 Hz, 1H), 2.11 (s, 3H), 1.99 (s, 3H), 1.86 (s, 3H); 13C NMR (100 MHz, CDCl3)  170.76, 170.24, 170.16, 168.32,
162.49, 155.37, 154.64, 154.07, 152.33, 151.72, 149.95, 136.30, 135.72, 133.40, 133.24, 133.12, 132.95, 128.30,
128.01, 127.93, 127.82, 127.64, 126.67, 126.55, 126.27, 126.04, 126.02, 125.81, 125.79, 119.68, 118.66, 118.20,
114.63, 102.95, 98.30, 95.37, 77.29, 76.08, 75.26, 74.44, 73.91, 73.45, 71.91, 70.96, 69.58, 68.70, 68.55, 67.54,
62.27, 55.75, 53.45, 51.49, 36.91, 21.28, 20.88, 20.67; HRMS (ESI): m/z calcd for C60H60Cl3N3O22 [M+Na]+:
1302.2626, found: 1302.2628.
11
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201901587
European Journal of Organic Chemistry
Methyl 2,4-di-O-benzyl-3-O-[methyl 5-(2,2,2-trichloroethoxycarbonylamino)-7,8,9-tri-O-acetyl-3,5-dideoxy
-4-O-(4-nitropicoloyl)-D-glycero-D-galacto-2-nonulopyranoylonate]--L-fucopyranoside (6j)
The disaccharide 6j and glycal ester 4b were obtained by the glycosylation of donor 1b (85 mg, 0.11 mmol) with
acceptor 5j[18] (20 mg, 0.055 mmol) using general glycosylation procedure in CH2Cl2/CH3CN (1:1) (1.1 mL) with
NIS (37 mg, 0.165 mmol)/TfOH (0.97 L, 11 mol) as promoter. The resulting residue was purified by silica gel
column chromatography (3:1→2:1, petroleum ether-EtOAc) to afford 6j (33 mg,  = 5/1, 55%) and 4b (48 mg,
1
61%) as white solids. -6j: Rf = 0.3 (1:1, petroleum ether-EtOAc); []25 +13.00 (c 0.20, CHCl3); H NMR (600
D
MHz, CDCl3)  9.07 (d, J = 5.2 Hz, 1H), 8.78 (d, J = 2.1 Hz, 1H), 8.23 (dd, J = 5.2, 2.2 Hz, 1H), 7.45 (d, J = 7.1 Hz,
2H), 7.37-7.29 (m, 6H), 7.26-7.24 (m, 2H), 5.47 (dd, J = 9.7, 2.1 Hz, 1H), 5.45-5.36 (m, 2H), 5.04-4.99 (m, 2H),
4.83 (d, J = 12.1 Hz, 1H), 4.68 (d, J = 11.5 Hz, 1H), 4.65 (d, J = 12.1 Hz, 1H), 4.60 (d, J = 3.7 Hz, 1H), 4.55 (d, J =
12.1 Hz, 1H), 4.39 (d, J = 12.1 Hz, 1H), 4.30 (dd, J = 12.5, 2.5 Hz, 1H), 4.20-4.17 (m, 2H), 4.12-4.08 (m, 1H),
4.01-3.98 (m, 1H), 3.91-3.86 (m, 1H), 3.82-3.80 (m, 2H), 3.66 (s, 3H), 3.35 (s, 3H), 3.08 (dd, J = 12.4, 4.6 Hz, 1H),
2.22 (s, 3H), 2.13-2.08 (m, 4H), 2.05 (s, 3H), 1.07 (d, J = 6.5 Hz, 3H); 13C NMR (150 MHz, CDCl3)  170.84,
170.28, 170.07, 166.63, 162.81, 154.81, 154.15, 152.53, 150.21, 139.15, 138.69, 128.62, 128.41, 128.29, 127.81,
119.78, 118.44, 100.57, 98.56, 95.38, 81.36, 75.62, 74.56, 74.52, 73.47, 71.76, 71.32, 67.69, 67.53, 65.44, 62.63,
55.16, 53.20, 51.64, 38.93, 21.25, 21.03, 20.88, 16.32; HRMS (ESI): m/z calcd for C46H52Cl3N3O20 [M+Na]+:
1094.2102, found: 1094.2104.
Methyl
5-acetamido-9-O-benzyl-4-O-benzoyl-2,6-anhydro-3,5-dideoxy-8-O-[methyl
5-(2,2,2-trichloroethoxycarbonylamino)-7,8,9-tri-O-acetyl-3,5-dideoxy-4-O-(4-nitropicoloyl)-D-glycero-D-
galacto-2-nonulopyranoylonate]-D-glycero-D-galacto-non-2-enonate (6m)
The disaccharide 6m and glycal ester 4b were obtained by the glycosylation of donor 1b (127 mg, 0.16 mmol)
with acceptor 5m (41 mg, 0.08 mmol) using general glycosylation procedure in CH2Cl2/CH3CN (1:1) (1.6 mL) with
NIS (55 mg, 0.24 mmol)/TfOH (1.45 L, 16 mol) as promoter. The resulting residue was purified by silica gel
column chromatography (2:1→1:1, petroleum ether-EtOAc) to afford 6m (40 mg,  4:1, 40%) and 4b (81 mg,
69%) as white solids. 6m: Rf = 0.25 (1:1, petroleum ether-EtOAc); 1H NMR (400 MHz, CDCl3)  9.07 (d, J = 5.3 Hz,
1H), 8.73 (d, J = 2.1 Hz, 1H), 8.23 (dd, J = 5.2, 2.2 Hz, 1H), 8.07 (d, J = 7.0 Hz, 2H), 7.56 (t, J = 7.4 Hz, 1H), 7.41 (t,
J = 7.8 Hz, 2H), 7.32-7.22 (m, 6H), 6.38 (d, J = 7.7 Hz, 1H), 5.54-5.41 (m, 4H), 5.40-5.33 (m, 1H), 5.07 (d, J = 9.6
Hz, 1H), 4.78 (d, J = 12.0 Hz, 1H), 4.66-4.52 (m, 4H), 4.41 (d, J = 12.1 Hz, 1H), 4.32 (dd, J = 12.2, 2.0 Hz, 1H),
4.27-4.24 (m, 1H), 4.23-4.14 (m, 2H), 4.14-4.04 (m, 3H), 4.04-3.97 (m, 2H), 3.93 (s, 3H), 3.83 (s, 0.75H), 3.71 (s,
3H), 2.92 (dd, J = 12.6, 4.5 Hz, 1H), 2.75 (dd, J = 12.6, 4.5 Hz, 0.25H), 2.23 (s, 3H), 2.21-2.16 (m, 7H), 2.15 (s,
0.75H), 2.05 (s, 0.75H), 2.03 (s, 3H); 13C NMR (100 MHz, CDCl3)  173.35, 171.28, 171.03, 170.16, 167.49, 165.50,
162.73, 162.35, 154.79, 154.16, 152.57, 149.97, 145.74, 138.47, 133.02, 130.55, 130.01, 128.44, 128.36, 127.74,
127.63, 119.86, 118.42, 107.65, 98.62, 95.26, 78.08, 74.55, 73.41, 72.42, 72.10, 70.76, 70.18, 68.65, 67.40, 67.26,
66.98, 63.24, 53.49, 52.52, 51.33, 48.40, 38.08, 23.30, 21.51, 21.06, 20.83; HRMS (ESI): m/z calcd for
C51H55Cl3N4O24 [M+Na]+: 1235.2164, found: 1235.2164.
Methyl
5-trifluoroacetamido-9-O-benzyl-4-O-benzoyl-2,6-anhydro-3,5-dideoxy-8-O-[methyl
5-(2,2,2-trichloroethoxycarbonylamino)-7,8,9-tri-O-acetyl-3,5-dideoxy-4-O-(4-nitropicoloyl)-D-glycero--D-
galacto-2-nonulopyranoylonate]-D-glycero-D-galacto-non-2-enonate (6n)
The disaccharide 6n and glycal ester 4b were obtained by the glycosylation of donor 1b (53 mg, 0.068 mmol) with
acceptor 5n (19 mg, 0.034 mmol) using general glycosylation procedure in CH2Cl2/CH3CN (1:1) (0.68 mL) with
NIS (22 mg, 0.10 mmol)/TfOH (0.60 L, 6.8 mol) as promoter. The resulting residue was purified by silica gel
column chromatography (2:1→1:1, petroleum ether-EtOAc) to afford 6n (18 mg, only, 42%) and 4b (32 mg, 65%)
1
as white solids. 6n: Rf = 0.2 (1:1, petroleum ether-EtOAc); []25 +32.86 (c 0.14, CHCl3); H NMR (600 MHz,
D
12
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201901587
European Journal of Organic Chemistry
CDCl3)  9.06 (d, J = 5.2 Hz, 1H), 8.74 (d, J = 2.1 Hz, 1H), 8.23 (dd, J = 5.2, 2.1 Hz, 1H), 8.07 (d, J = 7.2 Hz, 2H),
7.61-7.49 (m, 2H), 7.41 (t, J = 7.7 Hz, 2H), 7.31-7.23 (m, 5H), 5.50-5.42 (m, 3H), 5.44-5.38 (m, 1H), 5.06 (d, J = 9.3
Hz, 1H), 4.79 (d, J = 12.1 Hz, 1H), 4.76 (dd, J = 8.6, 2.5 Hz), (d, J = 12.1 Hz, 1H), 4.54 (d, J = 12.1 Hz, 1H),
4.48-4.35 (m, 3H), 4.30-4.22 (m, 2H), 4.11 (dd, J = 10.7, 2.3 Hz, 1H), 4.05 (dd, J = 12.6, 6.2 Hz, 1H), 4.03-3.96 (m,
2H), 3.94 (s, 3H), 3.90-3.84 (m, 1H), 3.84-3.81 (m, 1H), 3.73 (s, 3H), 2.91 (dd, J = 12.6, 4.7 Hz, 1H), 2.18 (s, 3H),
2.14-2.08 (m, 4H), 2.00 (s, 3H); 13C NMR (100 MHz, CDCl3)  171.54, 171.36, 170.58, 167.59, 165.51, 162.76,
162.02, 154.86, 154.08, 152.51, 150.11, 145.41, 138.08, 133.23, 130.28, 130.03, 128.55, 128.46, 127.85, 127.76,
119.80, 118.42, 107.42, 98.52, 95.36, 74.56, 73.53, 72.45, 72.16, 70.69, 69.32, 68.60, 68.51, 67.51, 67.40, 62.77,
53.55, 52.64, 51.40, 48.58, 37.93, 21.50, 20.85, 20.72; HRMS (ESI): m/z calcd for C51H52Cl3F3N4O24 [M+Na]+:
1289.1881, found: 1289.1884.
Methyl
[propan-2-yl
5-(2,2,2-trichloroethoxycarbonylamino)-7,8,9-tri-O-acetyl-3,5-dideoxy-4-O-
(4-nitropicoloyl)-D-glycero--D-galacto-non-2-ulopyranosid]onate (6o)
The compound 6o and glycal ester 4b were obtained by the glycosylation of donor 1b (50 mg, 0.064 mmol) with
acceptor 5o (2.5 L, 0.032 mmol) using general glycosylation procedure in CH2Cl2/CH3CN (1:1) (0.64 mL) with
NIS (22 mg, 0.096 mmol)/TfOH (0.57 L, 6.4 mol) as promoter. The resulting residue was purified by silica gel
column chromatography (4:1→3:1, petroleum ether-EtOAc) to afford 6o (20 mg,  only, 81%) and 4b (16 mg, 35%)
1
as white solids; 6o: Rf = 0.3 (3:1, petroleum ether-EtOAc); []25 +27.00 (c 0.20, CHCl3); H NMR (400 MHz,
D
CDCl3)  9.06 (d, J = 5.2 Hz, 1H), 8.73 (d, J = 2.2 Hz, 1H), 8.21 (dd, J = 5.2, 2.1 Hz, 1H), 5.51-5.35 (m, 3H), 5.12
(d, J = 9.2 Hz, 1H), 4.84 (d, J = 12.1 Hz, 1H), 4.38 (d, J = 12.1 Hz, 1H), 4.35-4.27 (m, 2H), 4.20 (dd, J = 12.6, 3.7
Hz, 1H), 4.09-4.03 (m, 1H), 3.85 (s, 3H), 3.81-3.73 (m, 1H), 2.85 (dd, J = 12.7, 4.7 Hz, 1H), 2.17 (s, 6H), 2.13-2.03
(m, 4H), 1.25 (d, J = 6.0 Hz, 3H), 1.07 (d, J = 6.2 Hz, 3H); 13C NMR (150 MHz, CDCl3)  170.87, 170.51, 170.14,
168.81, 162.67, 154.76, 154.09, 152.49, 150.28, 119.68, 118.36, 98.75, 95.47, 74.42, 71.39, 71.14, 69.08, 68.46,
67.50, 62.15, 52.83, 51.86, 38.72, 24.78, 23.16, 21.22, 21.03, 20.92; HRMS (ESI): m/z calcd for C28H34Cl3N3O16
[M+Na]+: 796.0897, found: 796.0895.
Methyl
[adamantan-2-yl
5-(2,2,2-trichloroethoxycarbonylamino)-7,8,9-tri-O-acetyl-3,5-dideoxy-4-O-
(4-nitropicoloyl)-D-glycero--D-galacto-non-2-ulopyranosid]onate (6p)
The compound 6p and glycal ester 4b were obtained by the glycosylation of donor 1b (37 mg, 0.048 mmol) with
acceptor 5p (3.7 mg, 0.024 mmol) using general glycosylation procedure in CH2Cl2/CH3CN (1:1) (0.48 mL) with
NIS (20 mg, 0.072 mmol)/TfOH (0.42 L, 4.8 mol) as promoter. The resulting residue was purified by silica gel
column chromatography (4:1→3:1, petroleum ether-EtOAc) to afford 6p (19 mg,  only, 90%) and 4b (9 mg, 26%)
1
as white solids. 6p: Rf = 0.3 (2:1, petroleum ether-EtOAc); []25 +16.88 (c 0.32, CHCl3); H NMR (400 MHz,
D
CDCl3)  9.06 (d, J = 5.3 Hz, 1H), 8.74 (d, J = 2.1 Hz, 1H), 8.21 (dd, J = 5.3, 2.1 Hz, 1H), 5.48-5.38 (m, 2H),
5.37-5.33 (m, 1H), 5.10 (d, J = 9.4 Hz, 1H), 4.83 (d, J = 12.1 Hz, 1H), 4.38 (d, J = 12.1 Hz, 1H), 4.30-4.23 (m, 2H),
4.18 (dd, J = 12.6, 4.7 Hz, 1H), 3.96 (d, J = 3.5 Hz, 1H), 3.86-3.76 (m, 4H), 2.91 (dd, J = 12.7, 4.7 Hz, 1H),
2.18-2.14 (m, 7H), 2.05 (s, 3H), 2.01-1.93 (m, 2H), 1.80-1.75 (m, 5H), 1.68-1.63 (m, 5H), 1.56-1.40 (m, 2H); 13C
NMR (150 MHz, CDCl3)  170.83, 170.46, 170.01, 168.80, 162.68, 154.76, 154.13, 152.49, 150.33, 119.65, 118.32,
98.67, 95.46, 77.91, 74.43, 71.48, 71.44, 68.63, 67.65, 62.19, 52.74, 51.82, 38.64, 37.62, 36.86, 36.50, 34.50, 33.24,
31.67, 31.56, 27.40, 27.08, 21.23, 21.04, 20.93; HRMS (ESI): m/z calcd for C35H42Cl3N3O16 [M+Na]+: 888.1523,
found: 888.1528.
Methyl
[adamantan-1-yl
5-(2,2,2-trichloroethoxycarbonylamino)-7,8,9-tri-O-acetyl-3,5-dideoxy-4-O-
(4-nitropicoloyl)-D-glycero-D-galacto-non-2-ulopyranosid]onate (6q)
The compound 6q and glycal ester 4b were obtained by the glycosylation of donor 1b (36 mg, 0.046 mmol) with
acceptor 5q (3.5 mg, 0.023 mmol) using general glycosylation procedure in CH2Cl2/CH3CN (1:1) (0.45 mL) with
13
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10.1002/ejoc.201901587
European Journal of Organic Chemistry
NIS (15 mg, 0.068 mmol)/TfOH (0.39 L, 4.5 mol) as promoter. The resulting residue was purified by silica gel
column chromatography (4:1→3:1, petroleum ether-EtOAc) to afford 6q (18 mg,  15/1, 91%) and 4b (8 mg, 24%)
1
as white solids. -6q: Rf = 0.3 (2:1, petroleum ether-EtOAc); []25 +23.08 (c 0.26, CHCl3); H NMR (400 MHz,
D
CDCl3)  9.05 (d, J = 5.3 Hz, 1H), 8.72 (d, J = 2.1 Hz, 1H), 8.20 (dd, J = 5.2, 2.2 Hz, 1H), 5.47-5.34 (m, 3H), 5.14
(d, J = 9.1 Hz, 1H), 4.88 (d, J = 12.1 Hz, 1H), 4.61 (d, J = 10.8 Hz, 1H), 4.39 (d, J = 12.1 Hz, 1H), 4.32 (dd, J = 12.8,
2.3 Hz, 1H), 4.23 (dd, J = 12.6, 3.6 Hz, 1H), 3.83 (s, 3H), 3.73-3.66 (m, 1H), 2.81 (dd, J = 12.8, 4.6 Hz, 1H), 2.18 (s,
3H), 2.17 (s, 3H), 2.15-2.09 (m, 4H), 2.05 (s, 3H), 1.86 (d, J = 3.0 Hz, 6H), 1.62-1.59 (m, 6H); 13C NMR (100 MHz,
CDCl3)  170.99, 170.86, 170.54, 169.95, 162.63, 154.81, 154.04, 152.46, 150.43, 119.60, 118.30, 97.90, 95.57,
79.18, 74.45, 71.72, 70.96, 68.83, 67.52, 61.98, 52.70, 52.13, 43.44, 41.08, 36.23, 31.23, 21.11, 21.01, 20.89; HRMS
(ESI): m/z calcd for C35H42Cl3N3O16 [M+Na]+: 888.1523, found: 888.1529.
p-Methoxyphenyl 3-O-[methyl 5-(2,2,2-trichloroethoxycarbonylamino)-7,8,9-tri-O-acetyl-3,5-dideoxy-4-O-
(4-nitropicoloyl)-D-glycero--D-galacto-2-nonulopyranoylonate]--D-galactopyranoside (7)
To a solution of 6i (96 mg, 0.075 mmol) in CH2Cl2/MeCN 4:1 (1.5 mL) were added 2 drops of water and DDQ
(85 mg, 0.375 mmol). The mixture was stirred under nitrogen for 2 h at 30 ºC . The reaction mixture was diluted with
CH2Cl2. The resulting organic solution was washed with saturated aq. NaHCO3 and water. The organic phase was
dried over Na2SO4, filtered, concentrated in vacuo. The residue was purified by column chromatography on silica gel
(1:1→1:2, petroleum ether-EtOAc) to afford 7 as a white solid (68 mg, 91%). 7: Rf = 0.2 (1:2, petroleum
1
ether-EtOAc); []25 +34.44 (c 0.18, CHCl3); H NMR (400 MHz, CDCl3)  9.04 (d, J = 5.2 Hz, 1H), 8.76 (d, J =
D
2.1 Hz, 1H), 8.23 (dd, J = 5.2, 2.1 Hz, 1H), 7.04 (d, J = 9.1 Hz, 2H), 6.82 (d, J = 9.1 Hz, 2H), 5.71-5.65 (m, 1H),
5.49-5.45 (m, 1H), 5.43-5.39 (m, 1H), 5.37 (d, J = 8.4 Hz, 1H), 4.95 (d, J = 7.8 Hz, 1H), 4.89 (d, J = 12.1 Hz, 1H),
4.45-4.41 (m, 2H), 4.31 (dd, J = 12.6, 2.3 Hz, 1H), 4.22 (dd, J = 9.5, 3.3 Hz, 1H), 4.16 (dd, J = 12.6, 4.7 Hz, 1H),
4.00-3.91 (m, 2H), 3.89 (s, 3H), 3.87-3.79 (m, 3H), 3.77 (s, 3H), 3.65 (t, J = 5.5 Hz, 1H), 2.95 (dd, J = 13.5, 4.9 Hz,
1H), 2.30 (dd, J = 13.6, 9.7 Hz, 1H), 2.19 (s, 3H), 2.14 (s, 3H), 2.03 (s, 3H); 13C NMR (150 MHz, CDCl3)  170.86,
170.70, 170.06, 168.79, 162.58, 155.37, 154.87, 154.18, 152.40, 151.31, 150.08, 119.93, 118.52, 118.44, 114.64,
102.14, 97.40, 95.48, 76.66, 74.42, 74.16, 71.16, 70.61, 69.08, 68.42, 68.10, 67.38, 62.62, 62.25, 55.79, 53.66, 51.73,
37.15, 21.26, 21.06, 20.87; HRMS (ESI): m/z calcd for C38H44Cl3N3O22 [M+Na]+: 1022.1374, found: 1022.1378.
p-Methoxyphenyl 2,4,6-tri-O-benzoyl-3-O-[methyl 5-(2,2,2-trichloroethoxycarbonylamino)-7,8,9-tri-O-acetyl-
3,5-dideoxy-4-O-(4-nitropicoloyl)-D-glycero--D-galacto-2-nonulopyranoylonate]--D-galactopyranoside (8)
To a solution of 7 (68 mg, 0.068 mmol) in pyridine/CH2Cl2 1:1 (1.4 mL) was added BzCl (0.18 mL, 1.02 mmol).
The mixture was stirred under nitrogen for 10 h at 30 ºC . The reaction mixture was quenched with MeOH until no
further heat was detected, concentrated in vacuo. The residue was purified by column chromatography on silica gel
(3:1, petroleum ether-EtOAc) to afford 8 as a white solid (76 mg, 85%). 8: Rf = 0.5 (2:1, petroleum ether-EtOAc);
1
[]25 +73.85 (c 0.26, CHCl3); H NMR (400 MHz, CDCl3)  9.00 (d, J = 5.3 Hz, 1H), 8.65 (d, J = 2.1 Hz, 1H),
D
8.20-8.05 (m, 7H), 7.64-7.55 (m, 3H), 7.52-7.43 (m, 6H), 6.96 (d, J = 9.0 Hz, 2H), 6.68 (d, J = 9.1 Hz, 2H), 5.69 (dd,
J = 10.1, 8.0 Hz, 1H), 5.67-5.59 (m, 1H), 5.54-5.41 (m, 2H), 5.35-5.27 (m, 2H), 4.98 (dd, J = 10.1, 3.4 Hz, 1H), 4.91
(d, J = 9.3 Hz, 1H), 4.76 (d, J = 12.1 Hz, 1H), 4.54-4.49 (m, 1H), 4.46-4.41 (m, 1H), 4.34-4.19 (m, 3H), 4.01 (dd, J =
12.6, 5.0 Hz, 1H), 3.95 (s, 3H), 3.90 (dd, J = 10.7, 2.5 Hz, 1H), 3.72 (s, 3H), 3.59-3.51 (m, 1H), 2.75 (dd, J = 12.5,
4.7 Hz, 1H), 2.20 (s, 3H), 2.01 (s, 3H), 1.89 (t, J = 12.3 Hz, 1H), 1.44 (s, 3H); 13C NMR (100 MHz, CDCl3)  170.86,
170.77, 170.42, 168.09, 166.00, 165.98, 165.45, 162.69, 155.66, 154.72, 153.98, 152.39, 151.53, 150.11, 133.74,
133.57, 133.36, 130.35, 130.27, 129.94, 129.88, 129.33, 128.67, 128.62, 128.51, 126.16, 119.68, 119.08, 118.32,
114.51, 101.34, 96.85, 95.36, 74.39, 71.77, 71.44, 71.24, 71.01, 68.38, 67.34, 66.88, 62.55, 62.31, 55.71, 53.55,
51.08, 37.56, 21.60, 20.90, 20.41; HRMS (ESI): m/z calcd for C59H56Cl3N3O25 [M+Na]+: 1334.2160, found:
1334.2159.
14
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201901587
European Journal of Organic Chemistry
p-Methoxyphenyl
[methyl
5-(2,2,2-trichloroethoxycarbonylamino)-7,8,9-tri-O-acetyl-3,5-dideoxy-4-O-
(4-nitropicoloyl)-D-glycero--D-galacto-2-nonulopyranoylonate]-(2→3)-(2,4,6-tri-O-benzoyl--D-galactopyra
nosyl)-(1→4)-3,6-di-O-benzyl-2-deoxy-2-azido--D-glucopyranoside (11)
To a solution of 8 (76 mg, 0.058 mmol) in CH3CN/CH2Cl2/H2O 5:2:1 (1.2 mL) was added CAN (127 mg, 0.232
mmol). The mixture was stirred under nitrogen for 1 h at room temperature. The reaction mixture was diluted with
CH2Cl2. The organic solution was washed with saturated aq. NaHCO3 and water. The organic phase was dried over
Na2SO4, filtered, and concentrated in vacuo. The residue was purified by column chromatography on silica gel
(3:1→2:1, petroleum ether-EtOAc) to afford a colorless syrup (56 mg). Then Cl3CCN (10 L, 0.098 mmol) and
DBU (1.8 L, 0.012 mmol) were added to a solution of the obtained syrup (56 mg) in CH2Cl2 (0.98 mL) at 0 ºC. The
resulting mixture was stirred under nitrogen for 1 h at 0 ºC . After completion of the reaction, the mixture was
purified by silica gel column chromatography (3:1→2:1, petroleum ether-EtOAc) to give 9 as a white solid (40 mg,
51% over two steps). The obtained donor 9 (40 mg, 0.029 mmol) and acceptor 10[22] (17 mg, 0.035 mmol) were
dissolved in dry CH2Cl2 (0.48 mL). Then freshly activated 4 Å molecular sieves (100 mg) was added. The mixture
was stirred under nitrogen for 0.5 h at room temperature. The reaction was cooled to -78 °C, then TMSOTf (1.1 L,
5.8 mol) was added. After being stirred for 2 h at the same temperature, the reaction was quenched with TEA,
diluted with CH2Cl2 and filtered. The filtrate was concentrated in vacuo to give a residue which was purified by
column chromatography on silica gel (2:1, petroleum ether-EtOAc) to afford 11 as a white solid (25 mg, 51%). 11: Rf
1
= 0.4 (1:1, petroleum ether-EtOAc); []25 +65.71 (c 0.14, CHCl3); H NMR (400 MHz, CDCl3)  8.99 (d, J = 5.2
D
Hz, 1H), 8.64 (d, J = 2.1 Hz, 1H), 8.21 (d, J = 7.0 Hz, 2H), 8.16 (dd, J = 5.2, 2.1 Hz, 1H), 8.04-7.99 (m, 3H),
7.60-7.45 (m, 5H), 7.44-7.29 (m, 8H), 7.26-7.21 (m 5H), 7.12-7.05 (m, 2H), 6.95 (d, J = 9.1 Hz, 2H), 6.74 (d, J = 9.0
Hz, 2H), 5.75-5.67 (m, 1H), 5.55 (dd, J = 9.9, 7.9 Hz, 1H), 5.49-5.42 (m, 1H), 5.40 (d, J = 3.4 Hz, 1H), 5.34 (d, J =
3.5 Hz, 1H), 5.32-5.24 (m, 2H), 5.13 (d, J = 7.9 Hz, 1H), 4.89 (dd, J = 10.0, 3.4 Hz, 1H), 4.83 (d, J = 10.3 Hz, 2H),
4.74 (d, J = 12.1 Hz, 1H), 4.67 (d, J = 11.5 Hz, 1H), 4.51 (d, J = 11.5 Hz, 1H), 4.34-4.26 (m, 2H), 4.22 (dd, J = 12.0,
6.8 Hz, 2H), 4.12 (dd, J = 10.7, 7.2 Hz, 2H), 4.07-4.00 (m, 2H), 3.88-3.84 (m, 4H), 3.77 (d, J = 9.3 Hz, 2H), 3.74 (s,
3H), 3.61 (d, J = 9.1 Hz, 1H), 3.58-3.51 (m, 1H), 3.36 (dd, J = 10.3, 3.6 Hz, 1H), 2.67 (dd, J = 12.6, 4.7 Hz, 1H),
2.11 (s, 3H), 1.98 (s, 3H), 1.83 (t, J = 12.3 Hz, 1H), 1.48 (s, 3H); 13C NMR (100 MHz, CDCl3)  170.86, 170.49,
170.34, 167.99, 165.89, 165.76, 165.09, 162.67, 155.37, 154.71, 153.98, 152.39, 150.74, 150.11, 138.41, 138.28,
133.54, 133.43, 133.23, 130.31, 130.03, 129.97, 129.93, 129.40, 128.78, 128.64, 128.44, 128.40, 128.22, 127.83,
127.69, 127.57, 127.52, 119.67, 118.30, 118.17, 114.70, 100.52, 97.74, 97.02, 95.33, 77.71, 76.24, 75.19, 74.41,
73.06, 72.14, 72.12, 71.26, 71.05, 71.00, 70.92, 68.25, 68.21, 66.94, 66.91, 62.83, 62.39, 61.73, 55.76, 53.49, 51.06,
37.56, 21.39, 20.84, 20.56; HRMS (ESI): m/z calcd for C79H77Cl3N6O29 [M+Na]+: 1701.3693, found: 1701.3694.
Acknowledgements
We appreciate the financial support from the National Natural Science Foundation (21772132, 21572145), the
Ministry of Science and Technology (2017ZX09101003-005-004), and the Fundamental Research Funds for the
Central Universities of China.
Conflicts of interest
The authors declare no competing financial interest.
Keywords: Sialylation • Synthesis • Sialic acid • 4-Nitropicoloyl • Hydrogen bonding
1. a) M. M. Furster, J. D. Esko, Nat. Rev. Cancer. 2005, 5, 526-542; b) A. Varki, Nature, 2007, 446, 1023-1029; c)
A. Varki, Trends Mol. Med. 2008, 14, 351-360.
15
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201901587
European Journal of Organic Chemistry
2. a) H. Shiya, Trends Glycosci. Glycotech. 2011, 23, 111-121; b) B. Sun, Curr. Org. Chem. 2016, 20, 1465-1476.
3. For reviews on synthesis of -sialosides, see: a) G. J. Boons, A. V. Demchenko, Chem. Rev. 2000, 100,
4539-4565; b) X. Chen, A. Varki, ACS Chem. Biol. 2010, 5, 163-176; c) C.-H Liang, C.-H. Hsu, C.-Y. Wu, Top.
Curr. Chem. 2015, 367, 125-150; d) C. De Meo, B. T. Jones, Adv. Carbohydr. Chem. Biochem. 2018, 75,
215-316.
4. a) M. P. Deninno, Synthesis, 1991, 8, 583-593; b) N. E. Byramova, A. B. Tuzikov, N. V. Bovin, Carbohydr. Res.
1992, 237, 161-175; c) S. Cai, B. Yu, Org. Lett. 2003, 5, 3827-3830; d) B. N. Harris, P. P. Patel, C. P. Gobble,
M. J. Stark, C. De Meo, Eur. J. Org. Chem. 2011, 4023-4027; e) T. J. Martin, R. R. Schmidt, Tetrahedron Lett.
1992, 33, 6123-6126; f) C.-H. Hu, K.-C. Chu, Y.-S. Lin, J.-L. Han, Y.-S. Peng, C.-T. Ren, C.- Y. Wu, C.-H.
Wong, Chem. Eur. J. 2010, 16, 1754-1760; g) J. M. Haberman, D. Y. Gin, Org. Lett. 2003, 5, 2539-2541; h) Y.
Li, X. Yang, Y. Liu, C. Zhu, Y. Yang, B. Yu, Chem. Eur. J. 2010, 16, 1871-1882; i) J. Wang, Q.-X. Lou, J.-J.
Rong, Y. Yang, Org. Biomol. Chem. 2019, 17, 6580-6584.
5. a) A. V. Demchenko, G. J. Boons, Tetrahedron Lett. 1998, 39, 3065-3068; b) C.-S. Yu, K. Niikura, C.-C. Lin,
C.-H. Wong, Angew. Chem. Int. Ed. 2001, 40, 2900-2903; c) C.-C. Lin, K.-T. Huang, C.-C. Lin, Org. Lett. 2005,
7, 4169-4172; d) H. Ando, Y. Koike, H. Ishida, M. Kiso, Tetrahedron Lett. 2003, 44, 6883-6886; e) S.-I Tanaka,
T. Goi, K. Tanaka, K. Fukase, J. Carbohydr. Chem. 2007, 26, 369-394; f) C. De Meo, U. Priyadarshani,
Carbohydr. Res. 2008, 343, 1540-1552; g) H. Tanaka, Y. J. Nishiura, T. Takahashi, J. Am. Chem. Soc. 2006, 128,
7124; h) A. Ishiwata, Y. Ito, Synlett 2003, 1339-1343; i) N. Komura, K. Kato, T. Udagawa, S. Asano, H.-N.
Tanaka, A. Imamura, H. Ishida, M. Kiso, H. Ando, Science 2019, 364, 677-680.
6. a) K. Okamoto, T. Kondo, T. Goto, Tetrahedron Lett. 1986, 27, 5233-5236; b) Y. Ito, M. Numata, M. Sugimoto,
T. Ogawa, J. Am. Chem. Soc. 1989, 111, 8508-8510; c) V. Martichonok, G. M. Whitesides, J. Am. Chem. Soc.
1996, 118, 8187-8191; d) T. Takahashi, H. Tsukamoto, H. Yamada, Tetrahedron Lett. 1997, 38, 8223-8226; e) J.
C. Castro-Palomino, Y. E. Tsvetkov, R. R. Schmidt, J. Am. Chem. Soc. 1998, 120, 5434-5440; f) J. M.
Haberman, D. Y. Gin, Org. Lett. 2001, 3, 1665-1668; g) S. Hanashima, S. Akai, K.-I. Sato, Tetrahedron Lett.
2008, 49, 5111-5114; h) T. Hayashi, G. Kehr, K. Bergander, R. Gilmour. Angew. Chem. Int. Ed. 2019, 58,
3814-3818; i) J. Chen, T. Hansen, Q.-J. Zhang, D.-Y. Liu, Y. Sun, H. Yan, J. D. C. Codee, R. R. Schmidt, J.-S.
Sun, Angew. Chem. Int. Ed. 10.1002/anie.201909177.
7. a) A. Hasegawa, T. Nagahama, H. Ohki, K. Hotta, H. Ishida, M. Kiso, J. Carbohydr. Chem. 1991, 10, 493-498;
b) K. Ikeda, K. Miyamoto, M. Sato, Tetrahedron Lett. 2007, 48, 7431-7435; c) C. De Meo, M. Farris, N. Ginder,
B. Gulley, U. Priyadarshani, M. Woods, Eur. J. Org. Chem. 2008, 3673-3677.
8. a) J. P. Yasomanee, A. V. Demchenko, J. Am. Chem. Soc. 2012, 134, 20097-20102; b) J. P. Yasomanee, A. V.
Demchenko, Angew. Chem. Int. Ed. 2014, 53, 10453-10456; c) S. G. Pistorio, J. P. Yasomanee, A. V.
Demchenko, Org. Lett. 2014, 16, 716-719; d) J. P. Yasomanee, A. V. Demchenko, Chem. Eur. J. 2015, 21,
6572-6581; e) A. K. Kayastha, X.-G. Jia, J. P. Yasomanee, A. V. Demchenko, Org. Lett. 2015, 17, 4448-4451.
9. a) Q.-W. Liu, H.-C. Bin, J.-S. Yang, Org. Lett. 2013, 15, 3974-3977; b) P.-C. Gao, S.-Y. Zhu, H. Cao, J.-S.
Yang, J. Am. Chem. Soc. 2016, 138, 1684-1688; c) W. Huang, Y.-Y. Zhou, X.-L. Pan, X.-Y. Zhou, J.-C Lei,
D.-M. Liu, Y. Chu, J.-S. Yang, J. Am. Chem. Soc. 2018, 140, 3574-3582; d) J.-C. Lei, Y.-X. Ruan, S. Luo, J.-S.
Yang, Eur. J. Org. Chem. 2019, 6377-6382; e) K. Zhu, J.-S. Yang, Tetrahedron, 2016, 72, 3113-3123; f) Y. Xu,
H.-C. Bin, F. Su, J.-S. Yang, Tetrahedron Lett. 2017, 58, 1548-1552.
10. a) S. Escopy, S. A. Geringer, C. De Meo, Org. Lett. 2017, 19, 2638-2641; b) Y.-F. Wu, Y.-F. Tsai, Org. Lett.
2017, 19, 4171-4174.
11. Y. Nakahara, H. Iijima, T. Ogawa, Tetrahedron Lett. 1994, 35, 3321-3324.
12. H. Hori, T. Nakajima, Y. Nishida, H. Ohrui, H. Meguro, Tetrahedron Lett. 1988, 29, 6317-6320.
13. Nitrile solvents are known to play a significant role in enhancing the -stereoselectivity of a sialosylation
reaction. For examples, see: a) C. Auge, B. Bouxom, B. Cavaye, C. Gautheron, Tetrahedron. Lett. 1989, 30,
2217-2220; b) C.-S. Yu, K. Niikura, C.-C. Lin, C.-H. Wong, Angew. Chem. Int. Ed. 2001, 40, 2900-2903; c) R.
16
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201901587
European Journal of Organic Chemistry
Schneider, C. C. Freyhardt, R. R. Schmidt, Eur. J. Org. Chem. 2001, 9, 1655-1661; d) K.-C. Lu, S.-Y. Tseng,
C.-C. Lin, Carbohydr. Res. 2002, 337, 755-760; e) C. De Meo, U. Priyadarshani, Carbohydr. Res. 2008, 343,
1540-1552; f) A. R. Mandhapati, S. Rajender, J. Shaw, D. Crich, Angew. Chem. Int. Ed. 2015, 54, 1275-1278.
14. I. Ohtsuka, N. Hada, M. Kanemaru, T. Fujii, T. Atsumi, N. Kakiuchi, Carbohydr. Res. 2015, 404, 9-16.
15. J. C. Lee, S. Francis, D. Dutta, V. Gupta, Y. Yang, J.-Y. Zhu, J. S. Tash, E. Schꢀnbrunn, G. I. Georg, J. Org.
Chem. 2012, 77, 3082-3098.
16. C.-S. Chao, C.-Y. Lin, S. Mulani, W.-C. Hung, K. K. T. Mong, Chem. Eur. J. 2011, 17, 12193-12202.
17. F. Xue, H.-F. Lu, L.-P. He, W.-F. Li, D. Zhang, X.-Y. Liu, Y. Qin, J. Org. Chem. 2018, 83, 754-764.
18. Z.-W. Guo, S.-J. Deng, Y.-Z. Hui, J. Carbohydr. Chem. 1996, 15, 965-974.
19. a) Y. E. Tsvetkov, R. R. Schmidt, Tetrahedron Lett. 1994, 35, 8583-8586; b) R. R. Schmidt, J. C.
Castro-Palomino, O. Retz, Pure Appl. Chem. 1999, 71, 729-744; c) C. De Meo, A. V. Demchenko, G.-J. Boons,
J. Org. Chem. 2001, 66, 5490-5497; d) H. Ando, Y. Koike, S. Koizumi, H. Ishida, M. Kiso, Angew. Chem. Int.
Ed. 2005, 44, 6759-6763.
20. M. J. Cieslewicz, D. L. Kasper, Y. Wang, M. R. Wessels, J. Biol. Chem. 2001, 276, 139-146.
21. P. K. Mondal, G. Liao, M. A. Mondal, Z.-W. Guo, Org. Lett. 2015, 17, 1102-1105.
22. F.-Q. Ding, A. Ishiwata, Y. Ito, Org. Lett. 2018, 20, 4833-4837.
17
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