Effect of Anomeric Configuration on Stereocontrolled α-Glycosylation of l -Fucose

Article abstract of DOI:10.1055/s-0037-1611311

In this letter, we report an approach to the stereoselective α-glycosylation of l -fucose that is exemplified by effect of anomeric configuration. The neighboring group participation is not compatible with α-glycosylation of l -fucose, therefore the remote participation by 4- O -Bz was employed to control the formation of 1,2- cis -glycosidic bond. Furthermore, we found the anomeric configuration of fucose donor is crucial to stereoselectivity of the glycosylated products. The α/β-mixed products were generated by using β-anomeric donor while the glycosyl donor in α configuration yielded products in high α-selectivity possibly due to the distinct pathway to forming the key intermediates. This phenomenon supplies the basis for the synthesis of complicated natural carbohydrates containing fucose α-glycoside, such as fucoidans, fucosylated N -glycans, and fucosylated chondroitin sulfates, etc.

Full text of DOI:10.1055/s-0037-1611311

SYNLETT
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© Georg Thieme Verlag Stuttgart · New York
2018, 29, A–F
letter
A
en
L. Wang et al.
Letter
Synlett
Effect of Anomeric Configuration on Stereocontrolled -Glyco-
sylation of L-Fucose
Lihao Wanga,c ◊
Fei Fana,c ◊
Haotian Wua,c
Lei Gaoa,c
Ping Zhanga,c
Tiantian Suna,c
Chendong Yanga,c
Guangli Yua,b,c
Chao Cai*a,b,c
OR
α/β mixtures
SEt
O
NIS, TMSOTf
OR
OBn
O
OBn
β donor
up to 90% de
OAc
OAc
BzO
BzO
fucosylation
anomeric
configuration
ROH
OR
SEt
O
α only
O
OBn
OBn
NIS, TMSOTf
OAc
• high stereoselectivity
• high yields
• broad acceptor scopes
OAc
BzO
BzO
α donor
a Key Laboratory of Marine Drugs, Ministry of Education, School of Medicine and Pharmacy,
Ocean University of China, Qingdao 266003, P. R. of China
caic@ouc.edu.cn
b Laboratory for Marine Drugs and Bioproducts, Qingdao National Laboratory for Marine Science
and Technology, Qingdao 266003, P. R. of China
c Shandong Provincial Key Laboratory of Glycoscience and Glycotechnology, School of Medicine
and Pharmacy, Ocean University of China, Qingdao 266003, P. R. of China
◊ These authors contributed equally to this work
Received: 25.08.2018
Accepted after revision: 08.10.2018
Published online: 23.11.2018
Glycosylation is considered as the central reaction in
carbohydrate chemistry.7 Robust glycosylation commonly
possesses the properties of high yields, and excellent regio-
and stereoselectivities, which supply fundamental building
blocks for accessing complex carbohydrates. Among these,
regioselectivity is usually achieved by the selective protec-
tion–deprotection process on acceptors. However, stereose-
lective glycosylation is more challenging because of the
flexible formation of a pair of diastereoisomers during gly-
cosylation. The neighboring group participation is the most
effective strategy to construct the 1,2-trans glycosides;8
furthermore, solvent effects9 and specific donors10 were
also employed to carry out high stereoselective glycosyla-
tion. The catalytic glycosylation with glycosyl imidate, ha-
lide, carbamate donors, and thioglycosides have been re-
cently reviewed with a focus on the development and ap-
plication of natural carbohydrates.11 Representative L-
hexose, such as L-fucose and L-iduronic acid, are mainly in
the form of -glycosides in the nature.12 The glycosylation
of -L-iduronic acid could be achieved by neighboring
group participation for assembly of heparin, heparan sul-
fate, and dermatan sulfate oligosaccharides.13 However, it is
still a challenge to form 1, 2-cis -glycosides, especially for
L-fucose.14 The fucose-containing glycans and glycoconju-
gates (Figure 1), such as fucoidans,15 fucosylated N-gly-
cans,16 as well as fucosylated chondroitin sulfates,17 mostly
exist in the form of -fucosides, which play multiple biolog-
ical functions, including anticancer, antiviral, and anticoag-
ulant activities, etc. Carbohydrate chemists have devoted
considerable efforts to the synthesis of complex fucose-
containing carbohydrates. Type I and II fucoidan oligosac-
charides were chemically synthesized from di- to hexasac-
charides. The stereoselective blockwise synthesis and acid-
promoted sulfation were developed by Nifantiev and co-
workers to prepare fucoidan fragments.18 Toshima’s group
DOI: 10.1055/s-0037-1611311; Art ID: st-2018-w0553-l
Abstract In this letter, we report an approach to the stereoselective -
glycosylation of L-fucose that is exemplified by effect of anomeric con-
figuration. The neighboring group participation is not compatible with
-glycosylation of L-fucose, therefore the remote participation by 4-O-
Bz was employed to control the formation of 1,2-cis-glycosidic bond.
Furthermore, we found the anomeric configuration of fucose donor is
crucial to stereoselectivity of the glycosylated products. The /-mixed
products were generated by using -anomeric donor while the glycosyl
donor in  configuration yielded products in high -selectivity possibly
due to the distinct pathway to forming the key intermediates. This phe-
nomenon supplies the basis for the synthesis of complicated natural
carbohydrates containing fucose -glycoside, such as fucoidans, fuco-
sylated N-glycans, and fucosylated chondroitin sulfates, etc.
Key words -L-fucoside, stereoglycosylation, thioglycoside donor,
anomeric configuration, remote participation
Carbohydrates widely exist in nature as oligosaccha-
rides, polysaccharides, and glycoconjugates in the form of
biomolecules such as peptides, proteins, lipids, etc.1 Natural
carbohydrates play crucial roles in versatile biological pro-
cesses from cell adhesion to chemical signaling in terms of
their structural complexity and diversity related to ano-
meric configurations, ring substituents, and conformational
variations.2 To obtain pure carbohydrate substrates, versa-
tile types of innovative approaches have been developed,
such as extraction from natural sources,3 chemical,4 enzy-
matic synthesis,5 and automated synthesis6 of oligosaccha-
rides from fundamental building blocks. Currently, increas-
ingly complex carbohydrates are being successfully ob-
tained through chemical approaches dedicated to the
applications in pharmaceutics, biomaterials, and food addi-
tives, as well as cosmetics and other fields.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2018, 29, A–F

B
L. Wang et al.
Letter
Synlett
reported that both natural fucoidan and 3,4-O-sulfated
tetrafucoside exhibited apoptosis-inducing activities
through activation of caspase-8 on MCF-7 cells.19 Synthesis
of fucoidan-mimetic glycopolymers with well-defined sul-
fation patterns via emulsion ring-opening metathesis po-
lymerization was recently developed by Cai and co-work-
ers.20 However, the stereocontrolled fucosylation of versa-
tile acceptors with different nucleophilicities have not yet
been well studied.
acetylation afforded thioglycoside donors 4 and 4 in one-
pot with high yields (82% for 4 from compound 3, 88% for
4 from compound 3).
SEt
OH
1. Ac2O, Py
1. MeONa, MeOH
O
O
OAc
OH
2. BF3•OEt2,
EtSH, DCM
OAc
OH
2. CSA, MeCN,
PhC(OEt)3, reflux
AcO
3a/3b, 2:3
3a: 37%; 3b: 56%
HO
1
SEt
SEt
1. NaH, BrBn, DMF
2. 1N HCl
O
O
OH
OBn
–OOC
OR
OR
O
O
OAc
O
O
3. Ac2O, Py
4a or 4b
BzO
O
O
O
RO
O
O
ORn
AcHN
O
OEt
4a: 82% from 3a
4b: 88% from 3b
HO n
O
Ph
RO
O
OR
OR
R = SO3– or H
R = SO3– or H
Scheme 1 Synthetic route of fucoside donor 4/4
OR
OR
fucoidan
fucosylated chondroitin sulfate
OH
O
To study the diastereoselectivity of the coupling reac-
tion between thiofucoside donor and acceptors, a common
acceptor 5 was synthesized from 2-chloroethanol.23 Com-
pound 4 was first chosen as a donor attributed to its high
isolate yield from the anomer mixture. The coupling reac-
tion that participated with thioglycoside was generally con-
ducted through an iodonium-assisted pathway. Thus, the
glycosylation system was handled with the promotion of
NIS/TMSOTf in CH2Cl2 to afford 6. However, /-mixed
products obtained subsequently were difficult to separate
by silica gel column, and only a very small amount of 6
was isolated. To analyze the ratio of 6 to 6 directly, a high
throughput reverse-phase high-performance liquid chro-
matograph (RP-HPLC) assay was applied for each coupling
reaction (Figure S1). Owing to the obstacles to the separa-
tion of 6, we synthesized 6 (74% from compound 7) by
Fisher glycosylation between compounds 2 and 5 (Scheme
S1) as a standard for RP-HPLC assay.
Moreover, the results of the coupling reaction between
4 and 5 under various conditions are summarized in Table
1. The glycosylation reactions were performed at –20 °C in
various solvents (Table 1, entries 1–3). We found that the
reaction in Et2O showed remarkable  selectivity of 86% de,
while CH3CN as a solvent showed relatively good  selectiv-
ity of –38% de. In addition, CH2Cl2 showed low anomeric se-
lectivity that was mainly affected by the intrinsic proper-
ties of donor and acceptor. The primary solvent effects were
obviously observed in that ether solvent facilitated  selec-
tivity compared with  selectivity in CH3CN. The observed
solvent-induced diastereoselectivity could account for the
molecular motion of dissociation and association in differ-
ent solvents.24 To improve the  selectivity of the coupling
reaction, we raised the temperature to 0 °C (Table 1, entries
4–6). The ratios of 6/6 in different types of solvents were
all advanced due to the increase of reaction temperature.
This phenomenon could be attributed to the improved for-
mation of remote participation and anomeric effect under
thermodynamic control. These results demonstrate that re-
action in Et2O at high reaction temperature could promote
O
H
HO
O
N
O
HO
HO
O
O
OH
O
H2N CO2H
OH
O
OH
O
HO
O
HO
OH
OH
HO
HO
N-glycan from chlorovirus
Figure 1 The representative structures of natural carbohydrates con-
taining -fucosides
The influence of anomeric configuration on the stereo-
selective formation of -fucosides is reported here. The
leaving group on  face of the fucoside donor preferred to
form oxocarbenium ions, leading to - and -mixed prod-
ucts upon attack by strong nucleophiles. On the contrary,
the high -selective fucosidic bonds were promoted by the
fucoside donor in  configuration and prior remote partici-
pation during the fucosylation for a wide range of acceptors.
The remote participation of 4-O-benzyl group on fucose
donors was reported to assist the formation of -fucosidic
linkage;21 moreover, the ether groups attached at C2 could
facilitate -anomer selectivity as well. However, these mul-
tiple effects were still not powerful enough to control the
complete formation of -fucosides, especially with strong
nucleophiles as acceptors. Thioglycoside is one of the most
commonly used donors due to its concise preparation and
better stability.22 Therefore, the thioglycoside 4 with 3,4-O-
diacyl group was synthesized as a donor for fucose glyco-
sylation. As shown in Scheme 1, fucose was peracetylated
under Ac2O/Py conditions followed by treatment with EtSH
in the presence of BF3·OEt2 to realize thioglycoside 3 as an
/ mixture. Notably, the mixture of anomers could be sep-
arated completely by a silica gel column to furnish the alter-
native anomers 3 and 3 (2:3), respectively. Compound
3/3 was deacetylated and protected with cyclic 3,4-O-or-
thobenzoate subsequently followed by 2-O-benzylation.
The regioselective ring opening of the orthoester and 3-O-
© Georg Thieme Verlag Stuttgart · New York — Synlett 2018, 29, A–F

C
L. Wang et al.
Letter
Synlett
the formation of -fucosidic linkage. Upon further increas-
ing the reaction temperature to even higher, however, room
temperature resulted in increased decomposition of thio-
glycoside 4 (Table 1, entry 7). Therefore, the optimum con-
dition for the formation of -fucosidic linkage could be 0 °C
in Et2O.
Table 2 Synthetic Scope Between -Fucosidic Donor with Different
Types of Acceptors
R
O
SEt
TMSOTf, NIS
R
OH
+
O
O
OBn
OBn
Et2O, 0 °C
OAc
11, 12,
14–17
OAc
BzO
18–23
4a
BzO
O
Table 1 Glycosylations of Fucose Donor with Alkyl Alcohol under Vary-
ing Conditions
N
HO
CF3
HO 6 N3
HO
N3
16
15
11
O
N3
N3
O
O
SEt
O
O
TMSOTf, NIS
slovent
O
N3
O
O
OH
O
+
HO
OBn
OBn
O
O
OBn
OAc
OAc
OAc
BzO
BzO
5
4a or 4b
6a or 6b
OH
O
OH
BzO
O
BzO
14
12
17
Entry
Donor
Solvent
T (°C)
/a
3.2:1
de (%)b
1
2
3
4
5
6
7
8
4
4
4
4
4
4
4
4
DCM
Et2O
–20
–20
–20
0
52
Entry Donor Acceptor /
Yield Product
(%)a
13.2:1
1:2.2
86
1
2
3
4
4
4
15
16
11
 only
 only
 only
98
CH3CN
DCM
Et2O
–38
64
O
O
6 N3
4.5:1
O
O
OBn
0
18.2:1
1:1.4
90
OAc
BzO
18
CH3CN
Et2O
0
–17
–
96
98
r.t.
0
decomposed
1:0
CF3
Et2O
100
OBn
a Anomeric ratio determined by RP-HPLC analysis.
OAc
BzO
b Diastereomeric excess (% de) = [ratio of  anomer (%)] – [ratio of  ano-
19
mer (%)]
O
With the thioglycoside 4 in hand as well, we further
investigated the glycosylation reaction under optimum con-
ditions, and interesting results were observed (Table 1, en-
try 8). An impressive  selectivity of nearly 100% de was ob-
tained and no -fucosidic products were isolated. Thus, we
speculated that the anomeric configuration of thioglycoside
could also be a critical factor influencing stereoselectivity
during formation of -L-fucosides.
Next, we investigated the efficiency and stereoselectivi-
ty of donor 4 by using a series of coupling reactions with
six acceptors from simple alcohols as strong nucleophiles to
versatile carbohydrate acceptors for the potential synthesis
of natural products.25 Among these acceptors, compounds
16 and 17 were commercially available, while the other
substrates 11, 12, 14, and 15 were synthesized as depicted
in Scheme S2. Acceptor 11 containing norbornene was pre-
pared by heating 10 and 2-aminoethanol in toluene. Termi-
nal azide containing alcohol 15 was furnished from 6-chlo-
rohexanol by treatment with sodium azide under alkaline
conditions. Compound 12 was procured through selective
removal of acetyl groups on 6 with 4% acetyl chloride in
methanol. Furthermore, 6 was successfully debenzylated
under mild oxidative conditions (NaBrO3/Na2S2O4) and
deacylated to afford compound 13. Subsequent transforma-
tion into the cyclic 3,4-O-orthobenzoate, acetylation, and
regioselective ring opening of orthoester gave acceptor 14.
N
O
O
O
OBn
OAc
BzO
20
4
4
12
 only
94
N3
O
O
OBn
O
BzO
O
OBn
OAc
BzO
21
5
4
14
 only
95
N3
O
O
OAc
O
BzO
O
OBn
OAc
BzO
22
6
4
17
 only
96
O
O
O
O
O
O
O
OBn
OAc
BzO
23
a Isolated yield.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2018, 29, A–F

D
L. Wang et al.
Letter
Synlett
α face
OR
Et
NIS
TMSOTf
ROH
SEt
S
O
O
O
OR
OBn
O
OBn
OBn
I
OBn
β face
OAc
OAc
OAc
×
BzO
BzO
OAc
donor 4b
BzO
BzO
TS1
α or β
sterically hindered
α face
Et
S
I
OBn
O
OR
SEt
O
NIS
TMSOTf
O
ROH
fast
O
OBn
OBn
α only
OBn
OAc
O
O
OAc
OAc
OAc
donor 4a
BzO
BzO
BzO
intramolecular SN2
Ph
TS2
Scheme 2 Proposed mechanism for the stereoglycosylation controlled by effect of anomeric configuration.
As shown in Table 2, the coupling reactions between do-
nor 4 and six acceptors demonstrate excellent stereoselec-
tivity, in which only -fucosidic products were isolated
with high yields. The straight-chain alkane acceptor 15 pos-
sesses strong nucleophilicity as similar as possible to accep-
tor 5, and high anomeric selectivities were found for both
coupling reactions. The decrease of nucleophilicity on an
acceptor by introducing fluorine atoms (Table 2, entry 2)
did not change the stereoselectivity obviously. Therefore,
the anomeric configuration of 4 was supposed to be the
crucial factor for the stereocontrolled fucosylation. Further-
more, acceptor 11 showed a similar  selectivity compared
with the above-mentioned substrates,26 which could be ap-
plied for the ring-opening metathesis polymerization
(ROMP) to access multivalent glycopolymers.27 Condensa-
tion with secondary hydroxyl groups on carbohydrate ac-
ceptors also exhibited excellent  selectivity. For example,
although the presence of 2-O-acetyl group on 14 decreased
nucleophilicity compared to 2-O-benzyl group on 12, the
high  selectivity during the coupling reactions was still
consistent. These representative acceptors (12 and 14) were
more favorable for the synthesis of oligofucosides with de-
fined sulfation patterns. Thus, it would be very helpful to
reveal their structure–activity relationship.18 Furthermore,
disaccharide 2328 was a fragment related to the distinct N-
glycans of chloroviruses, and the protocol presented here
promoted the access to chemical synthesis of the N-glycans
recently observed.16 Overall, the coupling reactions of do-
nor 4 with simple and complicated acceptors could all give
the products in  configuration. We speculated that the 
anomer of the thioglycoside donor facilitates the formation
of remote participation, leading to the desired products
with  configuration only.
among reaction intermediates, while the strong nucleophil-
ic acceptor was bound to oxocarbenium ions immediately
which showed lower stereoselectivity.
Based on the obtained results, the proposed mechanism
for the stereoselective glycosylation of donor 4/4 is de-
picted in Scheme 2. The ethylthio and 4-O-benzoyl group
on donor 4 located at the same orientation which hin-
dered the remote participation initially through the forma-
tion of oxocarbenium cation TS1. Thus, the acceptors could
attack the anomeric position from  and  faces, respective-
ly. The acceptors with strong nucleophilicity rapidly react
with TS1 to achieve lower  selectivity. However, TS1 is
mainly transformed into TS2, while the acceptors with
weak nucleophilicity are employed to afford moderate  se-
lectivity. Furthermore, the ethylthio and 4-O-benzoyl
groups on donor 4 are present at the opposite orientation,
thus possessing low steric hindrance. Remote participation
with the cleavage of the ethylthio group under an intramo-
lecular SN2 pathway forms TS2 quickly, which avoids the
formation of TS1. Therefore, the acceptors attack the ano-
meric position only from the  face which gives pure prod-
uct in  configuration for both strong and weak nucleo-
philes. Increasing the reaction temperature could improve
the formation of TS2 along with the higher  selectivity of
the anomeric effect.
In conclusion, facial-selective nucleophilic attack of a
glycosyl acceptor is attributed to steric and electronic prop-
erties of the oxocarbenium intermediate as well as stabili-
zation of the intermediate formed by remote participation.
The cleavage of the ethylthio group on  face followed by
successive 4-remote participation affords fucosides in a
high  configuration through the intramolecular SN2 path-
way. The present study is of great significance for the as-
sembly of complex natural carbohydrates and glycoconju-
gates containing -L-fucosides.
Furthermore, the  thioglycosides commonly in higher
isolated yields were also used as donors for the preparation
of -fucosidic linkages. According to the recent reports, the
coupling of -thioglycoside donors with carbohydrate ac-
ceptors generally afforded -configuration products in
terms of their low nucleophilicity.29 The results in our study
show that the preference of -configuration products could
be attributed to the high portion of remote participation
Funding Information
This work was financially supported by Fundamental Research Funds
for the Central Universities (201762002), Natural Science Foundation
of Shandong Province (ZR2016BB02), Primary Research and Develop-
© Georg Thieme Verlag Stuttgart · New York — Synlett 2018, 29, A–F

E
L. Wang et al.
Letter
Synlett
ment Plan of Shandong Province (2017GSF221002), Basic Research
Funds for Application of Qingdao (17-1-1-63-jch), National Natural
Science Foundation of China and NSFC-Shandong Joint Fund for Ma-
rine Science Research Centers (21602212, 31670811, U1606403), Ma-
jor Science and Technology Projects in Shandong Province
(15) Shan, X.; Liu, X.; Hao, J.; Cai, C.; Fan, F.; Dun, Y.; Zhao, X.; Liu, X.;
Li, C.; Yu, G. Int. J. Boil. Macromol. 2016, 82, 249.
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I.; Lanzetta, R.; Sturiale, L.; Palmigiano, A.; Garozzo, D.;
Molinaro, A.; Tonetti, M.; Etten, J. L. V. Angew.Chem. Int. Ed.
2016, 55, 654.
(2015ZDJS04002),
China
Postdoctoral
Science
Foundation
(2016M590664, 2017T100519), Shandong Provincial Key Laboratory
of Glycoscience Industry Alliance, Taishan Scholar Project Special
Funds, as well as Qingdao Scientific and Technological Innovation
(17) Zhao, L.; Wu, M.; Xiao, C.; Yang, L.; Zhou, L.; Gao, N.; Li, Z.; Chen,
J.; Chen, J.; Liu, J.; Qin, H.; Zhao, J. Proc. Natl. Acad. Sci. U.S.A.
2015, 112, 8284.
Center for Marine Biomedicine Development Grant.
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N. E.; Grachev, A. A.; Gerbst, A. G.; Nifantiev, N. E. J. Carbohyd.
Chem. 2008, 27, 429.
Supporting Information
Supporting information for this article is available online at
https://doi.org/10.1055/s-0037-1611311.
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(19) (a) Arafuka, S.; Koshiba, N.; Takahashi, D.; Toshima, K. Chem.
Commun. 2014, 50, 9831. (b) Kasai, A.; Arafuka, S.; Koshiba, N.;
Takahashi, D.; Toshima, K. Org. Biomol. Chem. 2015, 13, 10556.
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Li, C.; Yu, G. ACS Macro Lett. 2018, 7, 330.
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N. Synthesis 2006, 4017.
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References and Notes
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(25) General Procedure for Fucosylation of 4 with Acceptors
To a solution of compound 4 (10 mg, 0.0225 mmol, 1 equiv)
and acceptor (0.0248–0.225 mmol, 1.1–10 equiv) in 500 L
anhyd Et2O with argon protection was added 4 Å MS. The
mixture was stirred at room temperature for 0.5 h and then
cooled to 0 °C, then NIS (10.1 mg, 0.045 mmol, 2 equiv) and
TMSOTf (0.4 L, 0.00225 mmol, 0.1 equiv) were added. The
mixture was stirred for 0.5 h after which TLC indicated full con-
version and quenched with Et3N. The mixture was filtered,
evaporated, and purified by column chromatography to afford
product.
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(26) Analytical Data for Product 20
1H NMR (500 MHz, CDCl3):  = 8.03 (d, J = 8.1 Hz, 2 H), 7.60 (t, J =
7.4 Hz, 1 H), 7.47 (t, J = 7.7 Hz, 2 H), 7.33–7.27 (m, 5 H), 6.23 (s, 2
H), 5.50 (d, J = 3.0 Hz, 1 H), 5.35 (dd, J = 10.5, 3.2 Hz, 1 H), 4.93
(d, J = 3.4 Hz, 1 H), 4.60 (dd, J = 27.2, 12.1 Hz, 2 H), 4.26 (q, J = 6.5
Hz, 1 H), 3.91 (dd, J = 10.5, 3.5 Hz, 1 H), 3.85–3.80 (m, 1 H),
3.78–3.70 (m, 3 H), 3.26 (s, 1 H), 3.19 (s, 1 H), 2.60 (dd, J = 23.4,
7.0 Hz, 2 H), 1.91 (s, 3 H), 1.42 (d, J = 10.0 Hz, 1 H), 1.36 (d, J =
10.1 Hz, 1 H), 1.16 (d, J = 6.5 Hz, 3 H). 13C NMR (126 MHz,
CDCl3):  = 177.98, 177.95, 170.01, 165.98, 138.13, 137.82,
137.68, 133.22, 129.77, 129.67, 128.48, 128.34, 127.75, 127.69,
97.27, 73.49, 72.98, 72.15, 70.02, 65.02, 63.58, 47.83, 45.19,
42.89, 37.81, 20.83, 16.03. HRMS: m/z calcd for [C33H35NNaO9]+:
612.2204; found: 612.2201.
(7) Pellissier, H. Tetrahedron 2005, 61, 2947.
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(28) Analytical Data for Product 23
1H NMR (500 MHz, CDCl3):  = 8.08 (d, J = 7.3 Hz, 2 H), 7.64 (t,
J = 7.4 Hz, 1 H), 7.51 (t, J = 7.7 Hz, 2 H), 7.37–7.30 (m, 5 H), 5.82
(d, J = 3.6 Hz, 1 H), 5.53 (d, J = 2.6 Hz, 1 H), 5.37 (dd, J = 10.6, 3.2
Hz, 1 H), 5.01 (d, J = 3.5 Hz, 1 H), 4.75 (d, J = 12.1 Hz, 1 H), 4.60
(d, J = 5.6 Hz, 1 H), 4.56 (d, J = 12.2 Hz, 1 H), 4.41–4.36 (m, 1 H),
4.34 (d, J = 3.6 Hz, 1 H), 4.31 (d, J = 3.1 Hz, 1 H), 4.17 (dd, J = 8.6,
(14) (a) Abronina, P. I.; Zinin, A. I.; Romashin, D. A.; Malysheva, N. N.;
Chizhov, A. O.; Kononov, L. O. Synlett 2015, 26, 2267.
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© Georg Thieme Verlag Stuttgart · New York — Synlett 2018, 29, A–F

F
L. Wang et al.
Letter
Synlett
6.2 Hz, 1 H), 4.11 (dd, J = 9.1, 3.1 Hz, 1 H), 4.03–3.99 (m, 2 H),
1.96 (s, 3 H), 1.50 (s, 3 H), 1.42 (s, 3 H), 1.37 (s, 3 H), 1.29 (s, 3 H),
1.14 (d, J = 6.5 Hz, 3 H).13C NMR (126 MHz, CDCl3):  = 170.12,
166.05, 138.16, 133.28, 129.80, 129.72, 128.53, 128.49, 127.97,
127.68, 111.93, 109.22, 105.38, 96.00, 82.31, 81.08, 78.34,
73.80, 73.53, 72.20, 72.09, 70.43, 67.97, 65.27, 26.95, 26.87,
26.24, 25.36, 20.87, 15.88. HRMS: m/z calcd for [C34H42NaO12]+:
665.2568; found: 665.2565.
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C. Y.; Liu, G. J.; Du, W.; Zhang, Y.; Xing, G. W. Tetrahedron Lett.
2017, 58, 2109. (c) Zong, C.; Li, Z.; Sun, T.; Wang, P.; Ding, N.; Li,
Y. Carbohydr. Res. 2010, 345, 1522. (d) Zhang, X.; Yao, W.; Xu, X.;
Sun, H.; Zhao, J.; Meng, X.; Wu, M.; Li, Z. Chem. Eur. J. 2018, 24,
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© Georg Thieme Verlag Stuttgart · New York — Synlett 2018, 29, A–F