One-Pot Relay Glycosylation

Article abstract of DOI:10.1021/jacs.0c00447

A novel one-pot relay glycosylation has been established. The protocol is characterized by the construction of two glycosidic bonds with only one equivalent of triflic anhydride. This method capitalizes on the in situ generated cyclic-thiosulfonium ion as the relay activator, which directly activates the newly formed thioglycoside in one pot. A wide range of substrates are well-accommodated to furnish both linear and branched oligosaccharides. The synthetic utility and advantage of this method have been demonstrated by rapid access to naturally occurring phenylethanoid glycoside kankanoside F and resin glycoside merremoside D.

Full text of DOI:10.1021/jacs.0c00447

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Communication
One-pot Relay Glycosylation
Xiong Xiao, Jing Zeng, Jing Fang, Jiuchang Sun, Ting Li, Zejin Song, Lei Cai, and Qian Wan
J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.0c00447 • Publication Date (Web): 09 Mar 2020
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One-pot Relay Glycosylation
Xiong Xiao,† Jing Zeng,† Jing Fang,† Jiuchang Sun,† Ting Li,† Zejin Song,† Lei Cai,† Qian Wan*,†,‡
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†Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Huazhong University
of Science and Technology, 13 Hangkong Road, Wuhan, Hubei, 430030, P. R. of China
‡Institute of Brain Research, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, Hubei, 430030,
P. R. of China
Supporting Information Placeholder
consequently, required portion-wisely addition of one and even
more equivalents of activators for each glycosidic bond connection,
this strategy features the advantage that two glycosidic linkages
constructed by a single activator.
ABSTRACT:
A novel one-pot relay glycosylation has been
established. The protocol is characterized by the construction of
two glycosidic bonds with only one equivalent of triflic anhydride.
This method capitalizes on the in situ generated cyclic-
thiosulfonium ion as the relay activator, which directly activates the
newly formed thioglycoside in one-pot. A wide range of substrates
are well-accommodated to furnish both linear and branched
oligosaccharides. The synthetic utility and advantage of this
method have been demonstrated by rapid access to naturally
occurring phenylethanoid glycoside kankanoside F and resin
glycoside merremoside D.
Scheme 1. Glycosylation with glycosyl sulfoxides
a) Direct activation of glycosyl sulfoxide
SAr
Cl
O
O
Ph
Tf2O
(1.0 equiv)
DTBMP
3
Ar
S
eq 1
S
OPMB
O
O
Cl
O
+
+
O
OPMB
AcO
OPMB
(10.0 equiv)
HO
OPMB
AcO
1
2a
4
OMe
OMe
OH
1. capture
2. work up
Ar'
PhSOTf
A
eq 2
Ar'
PhS
In the odyssey of carbohydrate synthesis, great efforts have been
made to promote the efficiency of the glycosidic bond
construction.1 Among the tremendous achievements, activation of
glycosyl sulfoxides2 and thioglycosides3 presented as the most
popular glycosylation methods. It is well known that conventional
activation of glycosyl sulfoxides with triflic anhydride inevitably
generated active sulfenyl triflates (RSOTf) intermediates which are
powerful activators for sulfinyl/thioglycosides.4 To prevent these
side reactions resulted from the unbridled activity of RSOTf, large
excess of scavengers were usually introduced in these reactions
(Scheme 1a, eq 2).5 On the contrary, this chemistry shined a beam
of light on the cascade one-pot glycosylation strategy6,7 involving
sequential activation of glycosyl sulfoxides and thioglycosides by
harnessing the intermediate’s reactivity, albeit it was less
investigated.4i,8
3
high reactivity
5
(scavenger)
b) Remote activation of SPSB glycoside
SPSB
Tf2O
OTf
(1.0 equiv.)
S
S
S
O
ROH
O
O
+
OR
S
eq 3
0 o
C
B
6
low reactivity
c) One-pot relay glycosylation (this work)
Tf2O
(1.0 equiv.)
OTf
O
S
O
O
O
SR
SR
SPSB
+
HO
O
+
S
0 o
step 1
C
6
2
7
B
new glycosyl donor
new promotor
O
HO
S
O
O
O
8
O
O
RS
S
+
eq 4
30 o
C
step 2
9
10
We have recently reported an interrupted Pummerer reaction
mediated (IPRm) glycosylation strategy with S-2-[(propan-2-
yl)sulfinyl]benzyl (SPSB) glycosides as novel glycosyl donors
(Scheme 1b).9 It was observed that a cyclic thiosulfonium ion (B)
was generated upon activation of the SPSB glycosides with Tf2O.9c
Compared with sulfenyl triflates, the cyclic thiosulfonium ion (B)
was inactive under cryogenic conditions but reactive at ambient
temperature as a thioglycoside activator (see the ESI). Galvanized
on this observation, we hypothesized that one equivalent of Tf2O
can be used as an initial activator and the in situ generated
thiosulfonium ion can serve as the relay activator, which would
enables cascade activation of a SPSB glycoside and a thioglycoside
to form two glycosidic bonds in one-pot. This hypothesis would
supply a novel relay one-pot oligosaccharide assembly strategy
(Scheme 1c). Compared to the classical one-pot glycosylation
strategies, in which, each glycosylation step was independent,
Obviously, the thioglycoside (2) played a crucial role in the one-
pot relay glycosylation. It not only acted as the acceptor to couple
with the SPSB donor 6 but also served as part of newly generated
glycosyl donor 7 for the second glycosidic bond formation. Initially,
p-methylbenzyl thioglycoside 2ba was chose as first acceptor. The
reaction was first carried out at – 40 °C with 1.4 equiv of Tf2O as
activator, after 2ba was consumed completely (about 30 min), then
the terminal sugar 8a was added dropwise and the reaction
temperature was warmed up to 30 °C. To our delight, this one-pot
reaction proceeded smoothly. After 14 hours, the desired
trisaccharide 9a was isolated in 72% yield accompanied by 16%
yield of tetrasaccharide by-product 9a’. Occurrence of this by-
product indicated that the thioglycoside 2ba was still partially
activated by the thiosulfonium ion intermediate B even at – 40 °C.
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Further decreased the activation temperature of the first step led to
an inefficient coupling.
Consequently, we considered to tune the activity and stability of
the thioglycoside 2b by modification of the thiophenyl groups. It
was found that steric effect of thiophenyl group had greater impact
on the coupling efficiency compared to electronic effect.
Introducing ortho-methyl group on the phenyl ring (2bd) increased
the yield of 9a to 80% while slightly inhibited the occurrence of the
tetrasaccharide 9a’. Interestingly, warmed up the activation
temperature of the first step to 0 °C further increase the efficiency
of the one-pot reaction in this case. Among the test steric hindered
thiophenyl groups, ortho-ethyl thiophenyl (2be) performed as the
best. More hindered groups or halogen atoms located on ortho
position although sufficiently prevented the side reaction but also
stymied the coupling.
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Table 1. Tune the activity and stability of the thioglycoside 2b.a
OBn
O
HO
BnO
BnO
Tf2O (1.4 equiv)
4Å MS, DCM
OMe
(1.2 equiv)
OBn
O
S
8a
O
S
AcO
AcO
AcO
HO
BnO
SR
O
+
0 °C
step 1
30 °C
step 2
OBz
OAc
2b
(1.0 equiv)
6a
(1.2 equiv)
9
OAc
O
OBn
OBn
O
OBn
AcO
AcO
AcO
OBn
O
10
11
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O
O
BnO
O
O
AcO
AcO
O
BnO
O
BnO
O
BnO
+
AcO
AcO
BzO
9a
BzO
BnO
BnO
OMe
2
OMe
9a'
Having approved the concept, we then commenced to investigate
the substrate scope (Table 2).10 Various SPSB donors (6b-i),
thioglycoside (2b-g) and sugar or aglycon termini (8a-h) were then
examined. Among the tested SPSB donors, the peracylated
pyranoses, furanoses, deoxysugars and 2-aminosugars were all
performed very well. With respect to the thioglycoside 2, it was
found that o-ethylphenylsulfanyl (SoEP) group presented as better
leaving group for active thioglycosides (2be, 2c and 2d) while i-
propylsulfanyl (Si-Pr) is more suitable for inactive (disarmed)
thioglycosides (2e and 2f). Combination of these components with
the one-pot
Me
S
S
S
S
S
OMe
Cl
Me
2be
, 9a'
2ba
2bb
2bc
2bd
9a
(85%)
S
(7%)
b
b
b
b
9a
9a'
9a
9a'
9a
9a'
9a
9a'
(80%),
(72%),
(16%)
(70%),
(15%)
(75%),
(16%)
(11%)
9a
9a'
(83%),
(9%)
Me
F
Cl
OMe
S
S
S
S
Me
2bf
9a'
2bg
9a'
2bh
9a'
2bi
9a'
2bj
9a
9a
9a
9a
9a
9a'
(68%), (15%)
(81%),
(8%)
(72%),
(4%)
(70%),
(2%)
(78%),
(3%)
a
General procedure: Tf2O was added to the mixture of the SPSB
glycoside donor 6a and the thioglycoside 2b at 0 oC and stirred for
30 min., followed by the addition of acceptor 8a, then stirred at 30
oC for an appropriate time. b Tf2O was added at -40 oC.
Table 2. Substrate scopea
O
HO
Tf2O
O
O
O
O
4Å MS, DCM
8
(1.2 equiv)
O
SPSB
SR
O
O
+
HO
30 °C
step 2
0 °C
step 1
6
(1.2 equiv)
9
2
(1.0 equiv)
Thioglycosides 2:
SPSB donors 6:
AcO
AcO
OAc
O
OBn
OBz
O
OBz
BzO
HO
BnO
BnO
HO
HO
BnO
SPSB
O
BzO
2be
OAc
O
HO
BnO
O
SoEP
O
O
AcO
AcO
BzO
BzO
SPSB
SPSB
SPSB
SPSB
SoEP
S
o
EP
BzO
NPhth
OBz
6b
OAc
OBz
OBz
OBz
OAc
2c
2d
6c
6e
OBz
6d
SPSB
AcO
BzO
BnO
OBn
O
OBz
OBz
BzO
HO
AcO
BzO
BzO
O
O
O
SPSB
BzO
O
BnO
BnO
O
O
AcO
SBn
BzO
SiPr
SiPr
SPSB
HO
BzO
6h
OAc
BzO
BnO
OBz
OAc
OBz
OBz
6f
6g
6i
2e
2f
2g
Oligosaccharides
OBz
OAc
BzO
BzO
OAc
O
AcO
AcO
OBn
O
OBn
O
O
O
OBn
O
O
AcO
AcO
O
AcO
O
O
O
O
BzO
AcO
BzO
BnO
PhthN
AcO
BzO
AcO
OAc
O
BnO
BnO
O
AcO
O
O
BzO
BnO
BnO
OBn
O
BzO
O
BnO
O
BnO
OMe
6f
2be 8c
6d 2e 8b
9c
OBz
6c 2be
8a
, 71%
OBn
OBz
BnO
6e 2e
8c
O
OAc
b
BnO
9e,
, 70%
86%
OMe
9d
, 75%
9b
BnO
BnO
OMe
BnO
OBn
O
OMe
OAc
O
AcO
AcO
OBz
O
O
BzO
BzO
BzO
O
O
O
O
BnO
O
BnO
O
BnO
BnO
OBn
O
O
BzO
O
S
BzO
BnO
BzO
OAc
O
BzO
O
BzO
BzO
BnO
BnO
OPTB
O
O
BnO
O
OBz
BnO
BzO
O
6f 2be 8d
OBz
BnO
BnO
BnO
BzO
OBz
6h 2be 8f
6h 2c 8c
b,c
OMe
b,c
9f
, 73%
6g
BnO
2be 8e
9g
, 90%
b
OMe
asiaticoside trisaccharide
9h,
79%
b,c
OBz
BzO
BnO
9i
, 82%
OBz
O
OBz
O
OBz
O
OBn
O
OBz
O
BzO
BzO
O
BzO
BzO
O
BnO
O
OPTB
BzO
O
OBn
BnO
S
BzO
BzO
BzO
BzO
S
OBz
8g
OBz
BnO
BnO
BnO
O
O
O
O
O
BnO
S
O
O
O
BnO
6i 2f
O
BnO
BzO
OBz
BnO
i-Gb3 trisaccharide
SoEP
SiPr
OPTB
AcO
BnO
OMe
2d 8a
6b
,
63%d
OMe
79%b
9k
9j,
6b 8h
71%b,e
6b
9l,
2g
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a General procedure: Tf2O (1.0 equiv. to SPSB glycosides) was added to the mixture of 6 and 2 in DCM (0.1 M), 0 oC, 15 min, followed by
the addition of 8, then stirred at 30 oC for an appropriate time. bDTBMP (1.5 equiv) and CaCO3 (1.5 equiv) was added, SPSB donor 6 was
activated at -20 C. 3.0 equiv of terminal sugar or aglycon was used. 2.2 equiv of 6b was used. 6b (1.05 equiv), 2g (1.0 equiv), 8f (1.0
equiv), SPSB glycoside was activated at 0 oC.
1
2
3
o
c
d
e
relay glycosylation protocol auspiciously provided various
trisaccharides. It is worth noting that in certain cases, small amount
of tetrasaccharidal side-products composed of two repeated
tethering sugars (glycosyl part of thioglycoside 2) were still
observed. Lowering the activation temperature of the first step and
addition of 1.5 equiv of DTBMP as well as 1.5 equiv of CaCO3 was
able to suppress this type of side products and provided 9e-j in good
to excellent yield. The combination of these organic base and
inorganic base is essential to suppress the side reaction as which was
presumed to be resulted from the strong acid conditions.
Considering that the first step of the one-pot protocol was a fast
reaction and the second step is a slow reaction, the organic base was
used to speedily neutralize the acidity of the first step while the
inorganic base was used to buffer the acidity of the second step.
Undoubtedly, these conditions should augur well for acid-labile
substrates. Simply increasing the amount of DTBMP to 3.0 equiv
although was amenable to reduce the side reaction but at the
expense of attenuated overall yield because of the formation of the
orthoester by-products. In addition, 1,6-anhydro by-products were
observed when C6-benzyl substituted thioglycosides employed as
tethering sugars (see the ESI). It could be avoided by rising the
amount of the terminal sugar to 3.0 equiv (9f, 9g and 9i). Extended
this protocol to synthesize sugar moieties of natural occurring
third glycosidic bond. With this idea in mind, SPSB glycoside 6i,
thioglycoside 2f and OPSB glycoside 11a was then coupled
sequentially under the one-pot relay glycosylation conditions.
Subsequently, additional Tf2O as well as 8a was introduced into the
reaction system. Unfortunately, although the first three sugars
linked smoothly, the desired tetrasaccharide 12 was only isolated in
20% yield, along with 48% yield of 9j, in which, the terminal OPSB
group of 11a was reduced to OPTB group. This unexpected side
product was possibly raised form a competitive reduction reaction
of the sulfoxide group by a disulfide compound (10) released from
the SPSB group (see the ESI), because of the slow cyclization rate
in the OPSB activation step. A lot of efforts have been made to
suppress this side reaction. Finally, it was found that installing an
ethyl group on the ortho position of the OPSB (11b) auspiciously
increased the yield of tetrasaccharide 12 to 62%.
Having established the general applicability of the relay one-pot
glycosylation protocol in the efficient assembly of oligosaccharides,
we turned our attention to the synthesis of natural carbohydrates.
Kankanoside F (15) which showed vasorelaxant activity was
isolated from the Orobanchaceae parasitic plant (Cistanche
tubulosa).13 Kankanoside F bears a branched trisaccharide moiety
and a phenylethanoid aglycon. A regioselective glycosylation and
relay glycosylation approach was incorporated into the synthesis of
this molecular. Initially, two SPSB glycosides 6b and 6j was
regioselectivity coupled with 3,6-diol acceptor2h successively, then
phenylethanoid aglycon 13 was introduced. This procedure
afforded trisacchridal glycoconjugate 14 in 63% yield in one-pot.
The global deprotection of 14 eventually furnished kankanoside F
efficiently.
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7
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12
13
14
15
16
17
18
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12
glycoconjugates successfully offered asiaticoside11 and i-Gb3
trisaccharides (9i, 9j). Most importantly, the latent 2-[(propan-2-
yl)sulfanyl]benzyl (OPTB) group located at the reducing terminus
would allow the downstream installation of the aglycons by means
of IPRm glycosylation. By employing 2d possessing two free
hydroxy groups as tethering sugar, the assembling of a desired
tetrasaccharide 9k with three newly formed glycosidic bonds was
achieved in 63% yield. This success stimulated us to take chances
to assembly a branched sugar, that is activation of disarmed 6b with
Tf2O to couple at O-6 position of 8h followed by subsequent
activation of armed 2g to link at O-4 position of newly formed
disaccharide. To our delight, this protocol effectively furnished the
branched trisaccharide 9l in 71% yield.
Scheme 3. Total synthesis of kankanoside F
SPSB
O
4Å MS
AcO
OH
AcO
AcO
Tf2O (1.2 equiv)
DTBMP (1.5 equiv)
CaCO3 (1.5 equiv)
DCM
SoEP
AcO
OAc
(1.5 equiv)
OBz
OH
6j
Tf2O (1.5 equiv)
13
(2.0 equiv)
O
O
BzO
BzO
BnO
SPSB
+
HO
0 °C, 15 min
step 1
30 °C, 24 h
step 3
0 °C, 1h
step 2
OBz
(1.2 equiv)
OBz
(1.0 equiv)
2h
6b
OBz
O
OH
Scheme 2. Construction of three different glycosidic linkages in one-
pot
BzO
BzO
O
O
HO
HO
O
OBz
BnO
1. NaOMe, MeOH,
50 °C
OH
HO
O
O
O
2f
(1.0 equiv)
O
O
O
OBz
2. 30% Pd/C, MeOH
rt
OAc
Tf O
(1.3 equiv)
OH
2
O
O
OH
AcO
DTBMP (1.5 equiv)
CaCO3 (1.5 equiv)
DCM
HO
OAc
OAc
(63% three steps one-pot)
61%, two steps
14
15
Kankanoside F
AcO
OH
OBz
O
8a
(2.0 equiv)
(1.3 equiv)
BzO
BnO
6i
HO
11a 11b
or
(1.3 equiv)
OH
Tf O
2
SPSB
-20 °C, 30 min
0 °C, 30 min
30 °C, 14 h
step 2
As a final endeavor to demonstrate the utilitarian potential of the
protocol, a structurally more complex resin glycoside merremoside
D14 was chose as synthetic target. Merremoside D displayed
significant activity capable of transporting Na+, K+, and Ca2+ ions
across human erythrocyte membranes and antiserotonic activity.15
It possesses a tetra-rhamnose backbone which were connected by
1,4-α-linkages and a 21-membered macrolactone. O’Doherty and
co-workers have reported an elegant synthetic route toward the first
total synthesis and the structural refinement of Merremoside D by
virtue of the de novo synthetic strategy.16 We intended to synthesize
this molecular with two key one-pot relay glycosylations. The first
one-pot comprised the coupling of SPSB glycoside 6h,
thioglycoside 2i and a long-chained alcohol, 11(s)-jalapinolate 16.
This protocol furnished 17 in overall 83% yield albeit in an  to 
ratio of 2.8:1. Further hydrolyzation of the ester groups of 17
produced acid 18 possessing three continuous free hydroxy groups.
The ensuing site-selective macrolactonization of 18 presented as a
OBn
step 1
step 3
(1.3 equiv)
OBz
BzO
BnO
OPSB
O
OBz
OBn
OBn
O
OBz
S
OBn
O
O
O
BnO
O
O
O
BnO
O
BnO
O
HO
BnO
BzO
BzO
BnO
BzO
OMe
12
R
11a,
9j
)
with
with
20% (48% of
11b, 62%
11a,
11b
R = H
, R = Et
Encouraged by the successes on the construction of two
glycosidic linkages in one-pot by virtue of the relay-glycosylation
strategy, we then embarked on the building of three linkages in one-
pot. We conjectured that 2-[(propan-2-yl)sulfinyl]benzyl (OPSB)
glycosides would be orthogonal to the one-pot relay glycosylation
conditions. Consequently, employing OPSB glycoside (such as 11)
as the third sugar in the one-pot relay glycosylation sequence would
successfully create trisaccharide with an OPSB terminal which
could be activated by additional of Tf2O for the formation of the
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large obstacle as witnessed by the failures of known
1
2
3
4
5
6
7
8
macrolactonization conditions (see the ESI). Draw inspiration
from the cation-n interaction mediated site-selective acylation
reaction reported by Tang et al,17 utilization of 1.5 equiv of (S)-
BTM (benzotetramisole) along with 1.0 equiv of Piv2O as
esterification reagents surprisingly accomplished the site-selective
macrolactonization to afford 19 in 72% yield. The following site-
selective installing levulinoyl (Lev) group on C2’ position was
relied on the (R)-BTM mediated acylation reaction, which
produced 20 readied for the second one-pot reaction. Subsequent
second one-pot glycosylation promisingly produced the desired
tetrasccharide 21 in 72% yield. Global deprotection eventually
furnished the merremoside D (22) in 84% yield.
The Supporting Information is available free of charge on the ACS
Publications website. Experimental procedure, optimization tables
and characterization data for all products.
AUTHOR INFORMATION
Corresponding Author
* wanqian@hust.edu.cn
ORCID
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Qian Wan: 0000-0001-9243-8939
Jing Zeng: 0000-0001-9116-9861
Scheme 4. Total synthesis of merremoside D
COOMe
COOMe
C5H11
C5H11
Notes
Tf2O (1.3 equiv)
DTBMP (1.5 equiv)
CaCO3 (1.5 equiv)
DCM, -20 °C, 30 min
OH
(1.3 equiv)
30 °C, 20 h
The authors declare no competing financial interests.
S
16
SPSB
O
O
O
O
HO
+
BzO
O
O
BzO
O
first one-pot
O
OBz
O
O
ACKNOWLEDGMENT
BzO
BzO
OBz
6h
(1.3 equiv)
2i
(1.0 equiv)
We thank the National Natural Science Foundation of China
(21877043, 21772050, 21672077, 21761132014), the State Key
Laboratory of Bio-organic and Natural Products Chemistry
(SKLBNPC13425), the Fundamental Research Funds for the
Central Universities, HUST (2019kfyXKJC080, 2019JYCXJJ046,
2017KFYXJJ150) for support. We appreciated the Analytical and
Testing Centers of Huazhong University of Science and
Technology and School of Pharmacy for NMR and HRMS tests.
We thank Professor Hao Xu (Brandeis University) for helpful
discussions.
S
17
, 17
(61%)
(22%)
N
Ph
N
COOH
(S)-BTM
C5H11
O
C5H11
KOH (10 equiv)
CH3OH/H2O (9:1)
60 °C, 12 h
(S)-BTM (1.5 equiv), Piv2O (1.0 equiv)
DIPEA (3.0 equiv), DCE, reflux, 2 d
C = 0.0005 mol/L
O
O
O
O
O
O
O
HO
17
from
91%
O
72%
O
O
O
site-selective macrolactonization
OR
O
O
HO
HO
(R)-BTM
Lev2
OH
19 R = H
18
O
DIPEA
70 °C
20 R = Lev
56% (79% brsm)
Tf2O (1.3 equiv)
DTBMP (1.5 equiv)
CaCO3 (1.5 equiv)
DCM, -20 °C, 30 min
SPSB
SiPr
20
(2.0 equiv), 30 °C, 30 h
O
O
O
O
+
HO
O
second one-pot
O
OLev
O
O
REFERENCES
6k
(1.3 equiv)
2j
(1.0 equiv)
C5H11
O
C5H11
O
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O
1) N2H4, Ac2O, pyriding, DCM
2) AcOH-H2O, 65 °C
O
O
O
O
O
O
HO
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HO
O
O
84%
O
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OLev
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OH
O
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O
OLev
21
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O
O
OH
O
O
O
O
(72%)
O
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HO
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22
OH
O
Merremoside D
In conclusion, we have developed
a
novel one-pot relay
oligosaccharide and glycoconjugate assembly strategy. This
strategy relied on the hypothesis that an in situ generated cyclic
thiosulfonium ion (B) from the activation of SPSB glycosides was a
mild activator for thioglycosides. Compared to the classical one-pot
sequential glycosylation strategies, this strategy highlighted the
advantage that only one equivalent of exogenous activator was
required for construction of two glycosidic linkages. In a typical
activation process, the exogeneous activator Tf2O activated SPSB
glycosides to construct the first glycosidic linkage accompanied by
the in situ generation of cyclic thiosulfonium ion B. The cyclic
sulfonium ion then acted as a relay activator for the subsequent
activation of thioglycoside at a warmer temperature, consequently
created the second glycosidic linkage. Wide range of SPSB
glycosides, thioglycosides and terminal sugars or aglycones were
well accommodated to the protocol to furnish various liner or
branched oligosaccharides. The comprehensively application of
this protocol and a sites-elective macrolactonization reaction
allowed the expedient synthesis of resin glycoside merremoside D,
which extensively demonstrated the potential of this protocol.
ASSOCIATED CONTENT
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OTf
S
S
O
SPSB
Tf2O
O
relay activator
HO
initial activator
O
O
O
+
O
+
O
step 1
step 2
O
O
O
SR
HO
SR
O
new glycosyl donor
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