Current Organic Chemistry, 2005, 9, 179-194
One-Pot Glycosylation
Oligosaccharides
(OPG)
for
the
179
Chemical
Synthesis
of
Biao Yu,* Zunyi Yang and Hongzhi Cao
*State Key Laboratory of Bio-organic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry,
Chinese Academy of Sciences, 354 Fenglin Road, Shanghai 200032, China.
Abstract: This review provides a comprehensive survey of the “one pot glycosylation” (OPG) strategy for the chemical
synthesis of oligosaccharides, covering literatures from the first example reported by Kahne and Raghavan in 1993
through May 2003. The essence of the OPG is to distinguish the reactivity difference of a pair of the glycosylation donors
or acceptors so as to carry out two glycosylation steps sequentially without purification of the first-step coupling product.
Accordingly, the literature reports are grouped based on the major stereoelectronic factors causing the reactivity
differences, those include the “armed-disarmed effect”, “orthogonality of leaving groups”, “distinguishable acceptors”,
and “the hybrid”. “The hybrid” OPG procedure takes advantage of a combination of the reactivity disparity of a set of the
armed-disarmed donors, orthogonal leaving groups, as well as acceptors so as to proceed three or more steps of
glycosylation sequentially in one pot. Relevant conception and exploitation of the reactivity differences of the donors and
acceptors in the synthesis of oligosaccharides, which finally evolve the OPG or advance parallelly, are briefly described at
the beginning.
1. INTRODUCTION
The need for oligosaccharides and glycoconjugates of
defined composition to serve as molecular tools for
biological and medicinal studies have driven impetuously the
field of oligosaccharide synthesis especially since 1980s.
The flourishing alternatives thus developed for glycosylation
and protection, sometimes seemingly overgrown, have in
facts laid a ground for the assembly of oligosaccharides in
unprecedented efficient fashions [1-8]. Among the most
promising ones is the “one-pot glycosylation” (OPG)
strategy. An OPG carries out two or more glycosylation
steps sequentially without the requirement of protecting
group manipulation and intermediate isolation in between,
thus removes the major burden in the conventional chemical
synthesis of oligosaccharides in contrast to the natural
enzymatic way. To realize the OPG, the reactivity difference
of the donors/acceptors involved must be well distinguished
by a set of glycosylation conditions, and these conditions
sequentially performed in one pot need to be compatible.
Such a high demanding was first fulfilled by Kahne and
Raghavan, seems occasionally, in 1993 [9]. Through May
2003, nearly 50 fine designed OPGs have been published,
those from the group of Wong have been accounted [10].
And we present here a comprehensive treatment of this topic.
According to the major factors creating the reactivity
disparity of glycosylation donors/acceptors, the OPGs are
divided into four groups in the present review, namely,
“OPG steered by armed-disarmed donors”, “OPG steered by
orthogonal leaving groups”, “OPG steered by distinguishable
acceptors”, and “the hybrid OPG”. Within each group, a
chronological order is largely followed. Before going to
*Address correspondence to this author at the State Key Laboratory of Bioorganic and Natural Products Chemistry, Shanghai Institute of Organic
Chemistry, Chinese Academy of Sciences, 354 Fenglin Road, Shanghai
200032, China; Tel:(86) 21-54925131; Fax: (86)21-64166128; Email:
[email protected]
1385-2728/05 $50.00+.00
these topics, relevant conception and exploitation of the
reactivity differences of the donors and acceptors in the
synthesis of oligosaccharides, which finally evolve the OPG
strategy or develop parallelly, are briefly described.
2. RELEVANT CONCEPTS AND PROCEDURES
2.1 Historical Perception on the Reactivity of
Glycosylation Donors/Acceptors
In the seminal review of 1982, Paulsen concluded the
observations during oligosaccharide synthesis as such: “The
reactivities at the anomeric center of the glycosyl component
and of the OH group of the reaction partner depend very
strongly on the type of blocking pattern of the two
compounds. A variation of the blocking pattern can exert a
decisive influence on the coupling step. Conformation and
steric influences, and the molecular sizes of the two partners
are also significant” [1].
2.2 “Armed-Disarmed” Concept
The previous view on the reactivity difference of
glycosyl donors resulting from the blocking pattern was
enlarged by Fraser-Reid and coworkers, in 1988, to such a
level that it could be thoroughly distinguished and put into a
chemoselective glycosylation. [11]. Thus, n-pentenyl
glycoside 1, “armed” with the electron-donating benzyl
groups, was selectively activated with IDCP (iodonium
dicollidine perchlorate) to couple with n-pentenyl glycoside
2, which is “disarmed” with the electron-withdrawing acetyl
groups, providing disaccharide 3 in 62% yield without
detection of the self coupling products of 2 (Scheme 1). The
resulting “disarmed” 3 is obviously a donor capable of
further glycosylation under stronger conditions.
Fraser-Reid et al. rationalized the armed-disarmed effect
as such: “Reaction of a glycosyl donor with an appropriate
electrophile gives a positively charged intermediate which is
less favorable when there is an adjacent electronwithdrawing group (for example OCOR, as in a disarmed
© 2005 Bentham Science Publishers Ltd.
180
Current Organic Chemistry, 2005, Vol. 9, No. 2
OBn
O
BnO
BnO
Yu and Cao
OH
O
O
AcO
AcO
+
O
OBn
OAc
2
1
IDCP
OBn
O
AcO
AcO
O
BnO
BnO
O
O
OAc
OBn
3 (62%)
Scheme 1. A prototypical “armed-disarmed” glycosylation.
donor) than when there is an adjacent alkoxy group (as in the
armed counterpart). The latter therefore reacts faster and if,
in the reaction medium, there is a disarmed species carrying
a free hydroxyl group, a pathway based on Le Chatelier’s
principle can be envisaged that leads to products of crosscoupling with (virtually) none of the self-coupled analogue”
[12]. Based on these mechanistic rationales, the armeddisarmed concept, first recognized in n-pentenyl glycosides,
was rapidly extended to other types of glycosyl donors, such
as thioglycosides [13] and glycals [14]. And the torsional
effect caused by cyclic acetal protections was also realized
[15].
2.3
“Two-Stage
Activation”
and
“Orthogonal
Glycosylation” Strategies
After successful practice with thioglycosides and
glycosyl fluorides, Nicolaou and coworkers have developed,
since 1984, the “two-stage activation” strategy for the
efficient synthesis of oligosaccharides. [7, 16]. This
reiterative procedure utilizes the differential and orthogonal
reactivities of glycosyl fluorides, phenylthioglycosides, and
silyl ethers to achieve a sequential growth of the
oligosaccharide chain (Scheme 2).
OTPS
O
TBAF
SPh
NBS/DAST
R
OH
OTPS
O
SPh
O
SnCl2/AgClO4
R
F
R
OTPS
O
R
O
O
SPh
R
reiterate
Scheme 2. “Two-stage activation”. procedure for the reiterative
oligosaccharide synthesis.
The “orthogonal glycosylation” strategy described by
Kanie, Ito, and Ogawa, in 1994, activated the glycosyl
fluorides (Cp 2HfCl2, AgClO 4, -78 oC - rt) and thioglycosides
(NIS, AgOTf, -50 oC - rt) for glycosylation in an orthogonal
fashion, so that the requirement in the “two-stage activation”
for conversion of thioglycosides into fluorides for the next
step glycosylation was joyfully removed [17].
In complementary to the “orthogonal” effect, leaving
groups of a similar type but with different steric or electronic
nature were also found possible for chemoselective
glycosylations, such as glycosylations between phenylselenoglycosides and thioglycoside [18] and between
thioglycosides with different substituents on the anomeric
sulfur, termed “active-latent” donors [19]. In a broad sense,
“orthogonal effect” covers any distinguishable effects caused
by the leaving groups of the glycosyl donors on the
glycosylation selectivity.
2.4 “Two-Directional Glycosylation” Strategy
The reactivity difference between hydroxyl groups of the
acceptors, caused by steroelectronic effects, has enabled the
regioselective glycosylation to be a quite common practice
[20]. Furthermore, several protected forms, such as trityl [21]
and silyl ethers [22], which are normally inert toward
glycosylation, have been found to be capable of direct
glycosidation under some conditions. Thus an additional
level for reactivity manipulation in the oligosaccharide
synthesis is provided. Utilizing the reactivity disparity of
both the donors and acceptors, Boons and Zhu developed a
“two directional glycosylation” strategy [22-24]. A
remarkable example is shown in Scheme 3 [24]. The
protected hexasaccharide derivative of the tumor-associated
antigen Globo-H (14) was assembled from six well-designed
building blocks (4-9) via five successive steps of
glycosylation. Not a single step for protecting group
transformation was needed. Whereupon, the reactivity
disparity between the coupling pair of donors (ethyl
thioglycoside 4/phenyl thioglycoside 5, thioglycoside
10/fluoride 8) and acceptors (primary alcohol 6/secondary
alcohol 7, alcohol 11/TES ether 9) were fully distinguished.
3. OPG For the Chemical Synthesis of Oligosaccharides
The above mentioned “armed-disarmed”, “two-stage
activation”, “orthogonal glycosylation”, as well as the hybrid
“two-directional glycosylation” strategies are, in essence, a
matter of reactivity tuning, so as to perform two or more
steps of glycosylation successively without the need of
protecting group manipulation in between. OPG strategy
advances one step further where a set of compatible
conditions are used for the sequential glycosylation so that
the purification of the coupling intermediates is no long
required.
3.1 OPG Steered by Armed-Disarmed Donors
Application of the armed-disarmed concept for an OPG
was first established by Ley and coworkers in 1994 (Scheme
4) [25]. Coupling of the armed thioglycoside 15 with
disarmed 16 (NIS/TfOH) provided disaccharide 17 as the
sole coupling product (as monitored by TLC), without
detection of the self-coupling products of 16. Upon addition
of 18 and an additional portion of the promoters, the nascent
One-Pot Glycosylation (OPG) for the Chemical Synthesis of Oligosaccharides
Ph
SEt
OBn
O
Ph
BnO OBn
O
O
O
SPh
TrocHN
OBn
OH
TrocHN
F
OBn
12
BnO OBn
10
5
+
OBn
OBn
BnO
BnO
NIS/TMSOTf
67%, β
6
OBn
O
+
O
BnO
OBn
OTES
OBn
OH
HO(CH2)3NHZ
HO
O
O
O
O
O
F
NIS/TMSOTf
63%, β/α=1.5
BnO OBn
O
O
BnO
8
O
SPh
OBn
BnO
HO
O
70%, α
O
O
BnO
IDCP
OBn
BnO
OBn
BnO
4
+
BnO
Current Organic Chemistry, 2005, Vol. 9, No. 2 181
O
TESO
BnO
OBn
BnO
OBn
SEt
O
BnO
O
9
O
OBn
OBn
BnO
O
O
O
BnO
BnO
OBn
IDCP
71%, α
BnO
SEt
O
OBn
13
BnO
O(CH2)3NHZ
7
BnO
O
11
O(CH2)3NHZ
Ph
OBn
BnO
Cp2ZrCl2, AgOTf
89%, β
O
BnO
O
BnO
BnO
O
BnO
O
O
OBn
O
O
BnO O
TrocHN
O
O
O
OBn
O
BnO
OBn
OBn
OBn
14
BnO
O
BnO
O
O(CH2)3NHZ
OBn
Scheme 3. A “two-directional glycosylation” strategy toward the synthesis of a hexasaccharide derivative of the tumor-associated antigen
Globo-H.
disarmed 17 was activated and coupled with 18 to give
trisaccharide 19 in a satisfactory 62% yield, equal to a per
glycosylation yield of 79%.
In 1997, the OPG of armed-disarmed thioglycosides was
successfully employed in our total synthesis of the complex
resin glycoside, tricolorin A (Scheme 5) [26]. The armed
thioglycoside 21 was selectively activated at –15 oC
(NIS/TfOH) to glycosylate the disarmed 20, the resulting 22
was then activated in the presence of an additional portion of
NIS/TfOH at room temperature to couple with the newly
added acceptor 23, affording 24 in 43% isolated yield.
Similar protocol was also applied by Kondo et al., in
1998, in the synthesis of Le x oligosaccharide derivatives (28)
(Scheme 6) [27].
In 1999, Wong and coworkers contributed a general
procedure for the quantitative measurement of the relative
reactivities of the p-methylphenyl thioglycoside (STol)
donors which are either fully protected or have one hydroxyl
group exposed [28]. Thus, the structural effects of different
monosaccharide cores and different protecting groups on the
reactivity of each thioglycoside donors, which are previously
obscure or simply classified as armed-disarmed, were
accurately characterized and quantified. Furthermore, they
compiled the relative reactivity values (RRVs) into a
computer program, OptimerTM, which can suggest optimal
combinations of glycosyl building blocks for an OPG
synthesis of the target oligosacchrides.
A concept-prove assembly of 33 linear or branched
oligosaccharides based on RRVs was then provided. [29]. A
representative synthesis is shown in Scheme 7. The
thioglycoside donor 29 (RRV = 7.2 x 104), thioglycoside
donor/acceptor 30 (RRV = 142.9), and acceptor 32 (RRV =
0) were confidently chosen for the OPG synthesis of
trisaccharide 33.
Wong and coworkers have been expending the RRV
database while achieving programmable OPG synthesis of
biologically significant oligosaccharides [10]. An OPG
strategy for a rapid assembly of the Globo H hexasaccharide
182
Current Organic Chemistry, 2005, Vol. 9, No. 2
OMe
O
BnO
SEt
SEt
SEt
BnO
Yu and Cao
H
O
O
+
O
O
O
Et
O Me
HO
Me
OH
OBn
NIS/TfOH
SEt
H
O
O
O
Et
O Me
O
Me
O
O
OMe
BnO
BnO
22
OBn
OMe
17
O
NIS/TfOH
O
O
O
O
OH
OMe
O
O
NIS/TfOH
rt
Ph
O
O
O
OMe
18
O
OH
O
O
23
O
O
O
O
O
O
MeO
Et
H
OMe
OBn
OMe
O
O
BnO
O
BnO
OBn
21
NIS/TfOH, -15oC
O
O
BnO
Et
H
16
SEt
OMe
O
BnO
+
O
20
OMe
15
SEt
O
OMe
Ph
O
O
O
19 (62%)
H
OMe
BnO
O
O
O
O
O
O
Et
O
O
O
O
O
O
BnO
O
O
O Me
O
Me
O
Et
OBn
O
BnO
Scheme 4. OPG synthesis using armed-disarmed thioglycosides (15
vs. 16).
is shown in Scheme 8 [30]. The flow of the OPG synthesis
toward hexasaccharide 41 by thio-monosaccharides 34-36
and 39 and acceptor 40 was only interrupted at 37, where a
selective deprotection of the Lev group (37 → 38) was
required for the following glycosylation.
Disaccharides and oligosaccharides could be viewed as
monosaccharides with sugar substitutents, therefore, have
their own RRVs and can be used as components in the OPG.
In a synthetic route toward Lewis Y oligosaccharide hapten,
a colon-rectal cancer antigen determinant, Wong et al.,
realized a OPG synthesis of the hexasaccharide 45
employing monosaccharide donor 42, disaccharide
donor/acceptor 43, and disaccharide acceptor 44 (Scheme 9).
[31]. The RRV of 42 is only six times larger than the RRV of
43, nevertheless, a selective activation of 42 was achieved at
–70 oC to bis-glycosylate 43, the thio-function of which was
kept latent until the next glycosylation with 44.
Recently, Wong and coworkers added thioglycoside
building blocks for the sialylated oligosaccharides [32] and
the N-acetyllactosamine oligomers [33] to the Optimer
BnO
H
OBn
24
Scheme 5. OPG synthesis toward the resin glycoside tricolorin A
using armed-disarmed thioglycosides (21 vs. 20).
database. Shown in Scheme 10 is an OPG synthesis of the
acetyllactosamine trimer (49).
Adding stronger or more equivalents of the promoters or
raising the reaction temperature after the completion of the
first glycosylation is the usual way to force the second
glycosylation to take place in the reactivity-based OPG.
Oscarson and coworkers demonstrated that changing a
reaction medium could also have the OPG done (Scheme 11)
[34]. Thus, the reactivity-based selective coupling of the
thioglycosides 50 and 51 was achieved in Et2O
(NIS/AgOTf), but not in CH2Cl2, where a complex mixture
was produced due to the activation of both components.
Adding acceptor 52 and additional promoters in CH2Cl2, but
not in Et2O, realized the second glycosylation, affording 53
in high yield. Such a technique was later successfully used in
the OPG syntheses of the glucosamine oligosaccharides by
Baasov et al. (Scheme 12) [35]. In combination with the
armed-disarmed glycosylation with Troc and Phth protected
One-Pot Glycosylation (OPG) for the Chemical Synthesis of Oligosaccharides
O
OBz
O
OBz
O
OBz
OTBDPS
SPh
OBn
O
O
O
HO
Current Organic Chemistry, 2005, Vol. 9, No. 2 183
SPh +
BnO
O
OBn
OBn
OBz
26
25
29 (7.2x104)
OBz
O
O
O
OBz
SPh
OTBDPS
OBz
OBn
LevO
OBn
OBn
27
ROH, R = Gal/Lac derivatives
O
SPhMe
O
O
OBz
NIS/TfOH, -20 oC
OBz
BnO
OBz
O
O
O
OBz
O
31
OBn
OR
O
O
NIS/TfOH
OBn
p-MeOC6H4
28 (53-83%)
O
O
thioglycosides, they were able to realize a three-step OPG
synthesis of the glucosamine tetrasaccharide 58.
A new promoter system for the OPG of armed-disarmed
thioglycosides was reported by Mukaiyama et al. in 2000
(Scheme 13) [36]. The selective activation of the armed
thioglycoside 59 was achieved by TrB(C6F5)4/PhthNSEt.
Subsequent addition of NIS and acceptor 61 forced the
second glycosylation to afford the trisaccharide 62.
BzO
OBz
NBzO
O
OBn
HO
STol
O
NPhth
OBn
OBn
33 (74%)
Scheme 7. A representative RRVs-based OPG synthesis using
thioglycosides (29 vs. 30).
STol
OBnCl
36
35
OR
O
O
OBzN
HO
NHTroc
STol
O
O
OBz
BnO
BnO
OBn
O
BnO
OLev
BzO
OBz
OBzN
NBzO
O
O
O
NIS/TfOH, -20 oC, 67%
STol
O
OBnCl
NHTroc
OR
34
NPhth
32
O
LevO
Scheme 6. OPG synthesis toward Le oligosaccharides using
armed-disarmed thioglycosides (26 vs. 25).
OR
HO
O
TBDPSO
x
O
O
OBn
BnO
BnO
C6H4OMe-p
OBn
OBz
O
30 (142.9)
NIS/TfOH
O
O
O
BnO
SPhMe
HO
OBn
OBz
OBz
O
O
+
SPhMe
BnO
NIS/HOTf, -20 oC
O
LevO
37 R = Lev
38 R = H
STol
OBn
O
OBn
BnO
O
BnO
BnO
NBzO
O
O
TrocHN
O
O
BzO
OBz
OBzN
BnO
O
NIS/TfOH, -40 oC - rt, 62%
O
ClBnO O
OBn
O
OBn
OBn
41
HO
BnO
O
BnO
BnO
OBn
OBn
O
OBn
OPMP
39
OBn
BnO
O
O
BnO
BnO
OBn
40
Scheme 8. Programmable reactivity-based OPG toward the Globo H hexasaccharide using thioglycosides.
O
OBn
OPMP
184
Current Organic Chemistry, 2005, Vol. 9, No. 2
BnO
OBn
O
BnO
STol
OBn
O
Yu and Cao
OBn
O
O
OH
OBn
STol
HO
NHTroc
43 (RRV = 1.2 x 104)
BnO
42
-25 0C
NIS/TfOH, -70 oC
(RRV = 7.2 x 104)
BnO
OBn
O
OBn
HO
OLev
BnO
OBn
O
BnO
O
O
O
O
OBn
O
AcO
O
O(CH2)5CO2Me
NHTroc
OBn
OBn
OBn
OBn
OBn
OBn
OLev
NHTroc
O(CH2)5CO2Me
NHTroc
44 (RRV = 0)
OBn
O
O
O
O
BnO
OBn
O
O
AcO
45 (44%)
Scheme 9. Programmable reactivity-based OPG synthesis toward the Ley hapten using thioglycosides.
BnO
HO
AcO
OAc
O
OLev
OBn
AcO
OLev
OBn
O
AcO
O
STol
OBn
OLev
NHTroc
O
O
AcO
OR
NHTroc
48 (RRV = 0)
STol
NIS
NIS/TfOH, -35 oC
NHTroc
OBn
O
HO
47 (RRV = 246)
O
O
BnO
BnO
OBn
O
4
46 (RRV = 1.3 X 10 )
AcO
OAc
O
BnO
OBn
AcO
O
O
BnO
OLev
OBn
O
O
O
AcO
OLev
NHTroc
BnO
OBn
O
O
NHTroc
OBn
O
OBn
O
AcO
OLev
O
OR
NHTroc
49 (55%)
Scheme 10. Reactivity-based OPG synthesis of N-acetyllactosamine oligomers using thioglycosides.
SEt
OBn
O
HO
+
BnO
OBn
50
Ph
BnO
BnO
O
BnO
O
O
HO
51
SPh
NIS/AgOTf
Et2O
O
BnO OMe
52
Ph
NIS/AgOTf
CH2Cl2/Et2O
O
O
O
O
BnO
BnO
BnO
O
O
BnO
BnO
OMe
O
OBn
53 (84%)
OBn
Scheme 11. Reactivity-based OPG synthesis controlled by varying
solvents.
Although the armed-disarmed steered, or more broadly
“reactivity-based” OPG has been largely relied on
thioglycosides. In 1998, Ley and co-workers have noticed
the capability of armed-disarmed glycosyl fluorides for OPG
synthesis of oligosaccharides (Scheme 14) [37].
Recently, Mukaiyama and Chiba developed armeddisarmed glycosyl p-trifluoromethylbenzylthio-p-trifluoromethylphenyl formimidates (glycosyl thioformimidates) for
OPG synthesis (Scheme 15) [38]. The first step coupling
between armed 67 and disarmed 68 was performed in the
presence of a catalytic amount of TfOH at –78 oC, and the
subsequent second glycosylation took place upon addition of
the acceptor 69 and raising the temperature gradually to 0 oC.
3.2 OPG steered by the Orthogonal Leaving Groups
In 1994, Takahashi and coworkers firstly transformed the
“orthogonal glycosylation” procedure into an OPG fashion
(Scheme 16) [39]. Thus, glycosyl bromide 71, imidate 72, or
fluoride 73 was activated in the presence of AgOTf or
BF3OEt2 to couple with thioglycoside acceptor 74, the
resulting thio-disaccharide was then activated under the
action of the existing AgOTf or BF3OEt2 in combination
One-Pot Glycosylation (OPG) for the Chemical Synthesis of Oligosaccharides
AcO
Current Organic Chemistry, 2005, Vol. 9, No. 2 185
HO
O
AcO
AcO
SEt
OBn
O
BzO
BzO
+
NHTroc
54
O
BnO
BnO
SPh
55
NIS/TfOH
Et2O, -20 oC
SEt
+
OBn
NHTroc
SEt
OBzCl-p
60
59
TrB(C6F5)4/PhthNSEt
OH
HO
NIS/TfOH,
CH2Cl2/Et2O
-40 to -20 oC
O
BzO
BzO
O
BnO
BnO
NIS
SPh
BnO OMe
NPhth
61
56
NIS/TfOH,
-40 oC to rt
O
OAc
OBn
BnO
p-ClBzO
BnO
NPhth
O
O
O
O
BzO
BzO
PhthN
58 (63% )
OMP
PhthN
Scheme 12. Reactivity-based OPG synthesis of glucosamine
oligosaccharides.
with an additional portion of NIS to couple with the newly
added acceptor 75, leading to the corresponding trisaccharide
O
OBn
OBn
O
63
BnO
BnO
(76, 77). Shortly, Takahashi et al. applied this OPG protocol
to a successful assembly of the phytoalexin hexaglucan
(Scheme 17) [40].
At the same year, Chenault and Castro reported an OPG
protocol with orthogonal isopropenyl glycoside (82) and npentenyl glycoside (83). However, the overall yields were
not satisfactory (Scheme 18) [41].
Ley and coworkers paired selenoglycosides and
thioglycosides for OPG, while the orthogonality of these
OBn
OBn
O
OTBDPS
OH
O
OMe
BnO
BnO
OMe
OBn
OBzCl-p
Scheme 13. OPG using armed-disarmed thioglycosides with
TrB(C6F5)4/PhthNSEt/NIS as the promoter system.
O
TrocHN
BzO
BzO
O
62 (76%)
57
O
O
O
BnO
OMP
O
O
BnO
HO
BzO
BzO
O
AcO
AcO
TrocHN
BzO
BzO
OH
O
BnO
p-ClBzO
BnO
BnO
TBDPSO
O
OMe
F
64
O
Cp2HfCl2/AgOTf
F
OBz
OH
O
OMe
O
O
OMe
Cp2HfCl2/AgOTf
O
O
OMe
BzO
OMe
O
O
OMe
65
F
O
O
O
OMe
F
66 (37%)
Scheme 14. OPG synthesis using armed-disarmed glycosyl fluorides (63/64).
OH
O
BnO
BnO
BnO
67
R1 = p-CF3Ph
R2 = p-CF3Bn
OH
O
BzO
BzO
OBn
BzO O
NR1
O
2
SR
68
NR1
SR2
TfOH (10 mol%)
tBuOMe, -78 oC
O
BnO
BnO
BnO
OMe
69
-78 oC to 0 oC
Scheme 15. OPG using armed-disarmed glycosyl thioformimidates (67 vs. 68).
BnO
BnO
OBn
O
BnO
O
BzO
BzO
O
O
BzO
BnO
BnO
70 (92%)
O
BnO OMe
186
Current Organic Chemistry, 2005, Vol. 9, No. 2
AcO
AcO
OBzM
O
MBzO
MBzO
OH
O
Yu and Cao
SPh
OH
O
AcO
AcO
OAc
AcO OMe
75
74
OBzM
O
MBzO
MBzO
O
AcO
OBzM
AcO
AcO
OBzM
Br
AgOTf
NIS
O
AcO
AcO
OAc
O
AcO OC(NH)CCl
3
74
75
BF3 . OEt2
NIS
AcO
AcO
OAc
O
O
AcO AcO
AcO
O
AcO
72
O
AcO
AcO
OAc
O
74
75
.
NIS
O
AcO OMe
77 (62%)
AcO
AcO
O
AcO OMe
76 (84%)
71
AcO
AcO
O
77 (76%)
F
BF3 OEt2
AcO
73
Scheme 16. Prototypical representatives of OPG using orthogonal leaving groups (glycosyl bromide 71, imidate 72, or fluoride 73 vs.
thioglycoside 74).
OBzM
O
MBzO
MBzO
HO
AcO
AcO
O
OBzM
BnO
OBzM
O
O
79
NIS/TfOH
O
OC(NH)CCl3
TMSOTf
O
MBz
OH
OBnM
OBz
MBnO
MBnO
O BnO
O
MBnO
78
80
O
MBnO OMe
O
O
zM
OB BnO
O
O
O
O
BzO
AcO
AcO
O
MBzO
SPh
OAc
OBzM
MBzO
MBzO
MBzO
MBzO
O
OBzM
MBzO
zO
MB
81 (50%)
MBnO
MBnO
MBnO
O
AcO BnO
O
O
OBnM
O
MBnO OMe
Scheme 17. OPG synthesis of phytoalexin hexaglucan using orthogonal imidate (78) vs. thioglycoside (79).
pairs might require additional enforcement by the structural
effects (e. g., the armed-disarmed effect) (Scheme 19) [42].
The OPG with orthogonal glycosyl imidates and
thioglycosides might be more attractive for a practical
synthesis due to the popularity of these two types of donors.
Thus, we were able to prepare a group of natural diosgenyl
saponins in a highly efficient parallel manner. [43, 44]. A
representative is shown in Scheme 20. The first step
coupling between imidate donor 90 and thioglycoside
acceptor 91 required only 0.1 equivalent of TMSOTf at –70
o
C, while addition of 1.0 equivalent of NIS and the acceptor
92 promoted the second glycosylation.
Glycosyl phenylcarbonates have also been paired with
thioglycosides by Mukaiyama et al to achieve the OPG
synthesis of oligosaccharides (Scheme 21) [45, 46].
However, the overall yields (62%-85%) were lower
compared to those obtained by OPG using glycosyl imidates
in the first step. In addition, only 1→6 linkages were made
by this protocol. Mukaiyama and coworkers then also
modified the OPG with glycosyl fluorides and
thioglycosides. The first step glycosylation with the fluoride
donors was promoted by 20 mol% TfOH in the coexistence
of 5 Å MS in Et2O, generating the corresponding α anomers
predominantly in the absence of a neighboring control
(Scheme 22) [47]. These two OPG protocols were proved
One-Pot Glycosylation (OPG) for the Chemical Synthesis of Oligosaccharides
OPiv
OBn
OBn
O
OBn
O
PivO
PivO
Current Organic Chemistry, 2005, Vol. 9, No. 2 187
O
O
HO
BnO
+
OPiv
O
BnO
BnO
OBn
83
82
TMSOTf
O
SePh
86
O
NIS/TfOH
O
84
OBz
NIS/TfOH
OPiv
O
PivO
PivO
OBn
O
O
BnO
PivO
O
BnO
O
O
BnO
BnO
O
O
OMe
O
Scheme 18. OPG with orthogonal isopropenyl (82) vs. n-pentenyl
glycoside (83).
88
O
O
O
O
3.3 OPG Steered by Distinguishable Acceptors
In 1997, Boons and Zhu published an excellent OPG
protocol basing on the reactivity disparity between hydroxyl
groups of a glycosyl donor (109) and an acceptor (110)
(Scheme 24) [49]. In the right flask, the “disarmed” primary
OH of the thioglycoside donor 109 is less active than the
“armed” primary OH of the acceptor 110, therefore coupling
was managed to provide 112, leaving the “disarmed” OH
free. Meanwhile in the left flask, an “armed-disarmed”
coupling of thioglycosides 107 and 108 was carried out to
OTPS
O
O
O
OBz
OBn
O
BnO
O
OMe
OR
89 (50%)
Scheme 19. OPG with orthogonal selenoglycoside (86) vs.
thioglycoside (87).
give 111. Mixing the mixtures in the two flasks followed by
addition of another portion of the promoters (NIS/TfOH)
afforded hexasaccharide 113 in a remarkable 53% isolated
yield.
O
SEt
O
OBz
O
O
O
HO
AcO
CCl3
TMSOTf, -70 oC
AcO
O
OAc
91
O
AcO
O
O
HO
92
NIS, -10 0C
O
OAc
90
O
OBz
O
O
O
AcO
AcO
OAc
O
AcO
O
OAc
O
O
OR
OTPS
OMe
OMe
successful in the synthesis of the F1 α antigen (Scheme 23)
[48].
OBn
O
BnO
HO
OBn
OBn
O
O
85 (25%)
NH
SEt
87
OMe
O
O
OMe
O
OH
O
O
+
O
O
O
NIS/TESOTf
OTPS
OMe
OTPS
OH
O
OMe
O
93 (91%)
Scheme 20. OPG synthesis of a diosgenyl saponin with orthogonal imidate (90) vs. thioglycoside (91).
188
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Yu and Cao
OH
O
(PO)n
O
OPh
(PO)n
SR
O
94
O
BnO
BnO
F
+
TfOH (20 mol%)
Et2O, 0 0C
(PO)n
O
(PO)n
96
O
O
OH
NIS (2.0eq)
OMe
O
(PO)n
O
O
BnO
BnO
BnO
OBn
O
α/β = 5.7
BnO
OMe
O
BzO
BzO
Scheme 21. OPG synthesis of 1→6 linked trisaccharides with
orthogonal phenylcarbonates (94) vs. thioglycosides (95).
Valverde et al. employed the kinetic effect of an
intramolecular vs. intermolecular coupling to achieve the
OPG synthesis of the trisaccharide 117 (Scheme 25) [50].
Thus the intramolecular glycosidation of 114 took place
regioselectively on the 6-OH, then the second glycosidation
of the 3-OH with the newly added donor 116 provided 117.
Recently, Ning and Wang reported a facile OPG in the
synthesis of the unique trisaccharide fragment of the Motif E
of the Mycobacterium tuberculosis Cell Wall (Scheme 26)
[51]. The primary 6-OH of acceptor 118 was much active
than the secondary 5-OH, therefore steering the OPG via a
sequential addition of the two imidate donors (119 and 120)
of a similar type.
3.4 The Hybrid OPG
The first ever OPG protocol was reported by Kahne and
Raghavan in 1993, which utilized the reactivity disparity of
both the donors (sulfoxide 123 > sulfoxide 122) and the
acceptors (124 with OH > 123 with TMS ether) (Scheme 27)
[9]. Thus, the sequential two-step OPG needs not to be
controlled by a sequential addition of the coupling partner.
Instead, three reactants (122-124) were mixed, upon addition
of the promoter (TfOH), coupling between 123 and 124 took
place faster, generating 125, then a slow coupling between
122 and 125 produced 126. A molar ratio of 3 : 2 : 1 for 122
: 123 : 124 was thus arranged that the decomposed donors
122 and 123 during the coupling were compensated.
Ley and coworkers combined the orthogonality and the
armed-disarmed effect of donors for achieving the multi-step
linear OPG synthesis of mannose tpye oligosacchrides [5255]. A three-step OPG synthesis of the tetrasaccharide 133
was achieved in an unoptimized 10% yield, employing the
orthogonal pairs of the fluoride 127/selenoglycoside 128 and
the intermediate selenoglycoside 131/thioglycoside 132 and
the armed-disarmed pair of the intermediate selenoside
129/selenoside 130 for the successive glycosylation (Scheme
28) [52]. Utilizing the similar strategy, a four-step OPG
synthesis was also realized for the synthesis of the
pentasaccharide 140 from five monosaccharide building
blocks (fluorides 63, 64, selenosides 135, 137, and acceptor
139) (Scheme 29) [55].
OMe
100
O
BnO
BnO
(PO)n
97
SEt
OBz
99
98
OH
TrB(C6F5)4/NaIO4
O
BzO
BzO
OBn
95
TrB(C6F5)4 (cat.)
OH
OBn
O
O
O
BzO
BnO
BnO
101 (93%)
O
BnO OMe
Scheme 22. OPG syntheses with orthogonal glycosyl fluoride (98)
vs. thioglycoside (99).
BnO
OBn
OBn
O
BnO
X
+
O
HO
BnO
SEt
DCPhthN
MBzO
102 X = OCO2Ph
103 X = F
TrB(C6F5)4
or TfOH
BnO
NIS
OH
O
BnO
NHZ
N3
BnO
CO2Bn
OBn
O
O
MBzO
O
105
OBn
BnO
104
O
BnO
O
DCPhthN OBn
O
NHZ
BnO
106 (80% or 89%)
N3 O
CO2Bn
Scheme 23. OPG synthesis toward F1 α trisaccharide using
orthogonal glycosyl carbonate (102) or fluoride (103) vs.
thioglycoside (104).
In 1999, Takahashi and coworkers reported an OPG
protocol for branched synthesis of oligosacchaides
employing the combination of a pair of orthogonal bromide
and thioglycoside donors and an acceptor with a pair of
distinguishable OHs [56]. A representative example is
depicted in Scheme 30. To the mixture of bromide 71 (1.05
eq), thioglycoside 142 (2.0 eq), and acceptor 141 (1.0 eq),
AgOTf was added first to promote the coupling of 71 with
One-Pot Glycosylation (OPG) for the Chemical Synthesis of Oligosaccharides
BzO
OBn
O
BnO
BnO
BzO
OH
O
O
BzO
BzO
+
OH
O
BzO
O
SEt
BnO
Current Organic Chemistry, 2005, Vol. 9, No. 2 189
BzO
BzO
SEt
BzO
BzO
BzO
NIS/TMSOTf
NIS/TMSOTf
OBn
O
BnO
BnO
OBz
OH
BzO
O
OBz
BnO O
BzO
BzO
BzO
O
O
BzO
O
O
BzO
BzO
O
OMe
110
109
108
107
O
O
BzO
OBn
O
HO
BnO
SEt +
BnO
BzO
SEt
OBn
O
OMe
112
BzO
111
O
BnO
BzO
BnO
OBn
BnO
BnO
NIS/TMSOTf
O
BnO O
OBz
BzO
O
BzO
OBz
O
O
BzO
BzO
O
BzO
BzO
O
O
O
BzO
BzO
BzO
O
OBn
O
BzO BnO
BnO
113 (53%)
OMe
Scheme 24. OPG utilizing the reactivity difference between the OHs of donor (109) and acceptor (110).
OAc
O
TBDPSO
AcO
AcO
O
O
O
O
HO
HO
HO
O
AcO
AcO
AcO
AcO
OAc
O
SPh
114
116
SPh
O
OAc
O
115
OAc
O
AcO
AcO
O
O
HO
HO
NIS/AgOTf
O
OMe
O
O
O
O
OMe
O
OAc
O
TBDPSO
AcO
AcO
NIS/AgOTf
O
O
O
HO
117 (39%)
O
OMe
Scheme 25. OPG utilizing the reactivity difference of the OHs for an intramolecular vs. intermolecular coupling..
the active 6-OH, following addition of NIS/TfOH then
activated 142 to couple with the remaining 3-OH.
Employing this strategy, together with the previous linear
OPG with orthogonal donors, Takahashi et al. were able to
build a library of 72 trisaccharides on a Quest 210TM manual
synthesizer [57]. The branched and linear type OPG were
then combined in one pot for the synthesis of the
heptaglucan of the phytoalexin elicitor [58]. A remarkable
six-step OPG synthesis of this interesting glucan was
achieved on the manual synthesizer (Scheme 31) [59]. This
is so far the OPG assembly coupling the highest number of
saccharide building blocks. A little earlier, Muaiyama et al.
employed four blocks for an OPG synthesis of this
heptaglucan [60].
In 1999, we managed the synthesis of a bidesmosidic
triterpene saponin using a novel hybrid OPG protocol
(Scheme 32) [61]. Where the trityl ester (on 151) remained
latent during the glycosylation of the 3-OH with imidate 152
at –60 oC, but conducted ready cleavage upon raising the
temperature to rt. The resulting carboxylic acid 154 was then
glycosylated with imidate 155 at 0 oC without additional
O
OBz
HO
O
HO
OC(NH)CCl3
O
OBz
+
BzO
O
BzO
118
OBz
119
TMSOTf
-45 oC to rt
BzO
O
BzO
rt
OC(NH)CCl3
BzO
OBz
O
BzO
OBz
O
OBz
BzO
BzO
120
O
OBz
O
O
O
OBz
O
121 (71%)
Scheme 26. OPG synthesis of the Motif E trisaccharide based on
the reactivity difference of the two OHs of the acceptor (118).
190
Current Organic Chemistry, 2005, Vol. 9, No. 2
Yu and Cao
O
O
S
S
O
S
OCH3
O
+
TMSO
122 (3.0 eq)
TfOH (0.05 eq), -78 oC
fast
OBn
OBn
O
CH2Cl2/Et2O,
CHCCO2CH3
O
+
HO
123 (2.0 eq)
124 (1.0 eq)
S
SPh
O
O
O
OBn
O OBn
-70 0C
slow
O
OBn
O
125
HO
O
+
OBn
O
122
126 (25%)
O
Scheme 27. OPG synthesis of the ciclamycin trisaccharide based on the reactivity disparity of both donors (122/123) and acceptors (123/24).
FBnO
FBnO
OBnF
OAc
O
FBnO
FBnO
AgOTf
Cp2HfCl2
F
127
BnO
BnO
OBn
O
BnO
BnO
OMe
O
128
FBnO
FBnO
FBnO
FBnO
BnO
BnO
BzO
OMe
O
OH
OMe
O
O
OMe
O
O
SEt
133 (10%)
131
O
O
O
OMe
132
SePh
O OBn
O
BzO
OMe
OBz
O
OMe
O
O
OBnF
OAc
O
BnO
BnO
NIS/TfOH
O OBn
O
SePh
NIS/TfOH
SePh
OBnF
OAc
O
O
130
SePh
129
OH
O
OMe
O OBn
O
+
HO
OBz
OBnF
OAc
O
O
OMe
O
OBz
O
O
OMe
SEt
Scheme 28. A three-step OPG synthesis utilizing both orthogonal and armed-disarmed donors.
promoter. The trityl ether (on 155) remained intact during
the coupling, was directly glycosylated by thioglycoside 159,
prepared in another flask, to give the target molecule 160 in
a satisfactory 62% yield. The use of two (or more) flasks
provides another manual choice for controlling the OPG
sequence.
Nearly 15 years, since the discovery of the armeddisarmed effect of donors, brings Fraser-Reid and
One-Pot Glycosylation (OPG) for the Chemical Synthesis of Oligosaccharides
OBn
OBn
O
BnO
BnO
BnO
BnO
O
BnO
BnO
O
BnO
BnO
SePh
135
MeO
TPSO
O
O
AgOTf/Cp2HfCl2
O
O
O
OBn
O
F
O
BnO
BnO
134
F
O
OMe
OMe
O
OMe
OH
O
TPSO
OTPS
OH
O
OMe
O
AgOTf
Cp2HfCl2
OBn
OBn
O
OMe
+
OBn
OBn
O
OBn
F
63
Current Organic Chemistry, 2005, Vol. 9, No. 2 191
64
SePh
136
OBn
OBn
O
BnO
BnO
MeO
TPSO
O
O
OMe
OMe
BnO
O
O
O
BnO
BnO
MeO
OH
O
O
MeO
O
SEt
NIS/TfOH
O
O
BnO
O
SePh
137
NIS/TfOH
O
O
BzO
O
O
OH
O
OMe
O
MeO
OBz
OMe
OMe
O
BnO
BnO
O
O
OBz
OMe
O
OMe
139
O
TPSO
O
OMe
BzO
O
O
O
O
O
SePh
OMe
138
SEt
OMe
140 (8%)
BnO
BnO
OBz
O
O
OBn
OBn
O
Scheme 29. A four-step OPG synthesis utilizing both orthogonal and armed-disarmed donors.
OBzM
OBzM
MBzO
MBzO
MBzO
MBzO
O
HO
MBzO Br
71 (1.05 eq)
AcO
AcO
AcO
BnO
HO
O
BzO OMe
O
OAc
SPh
141 (1 eq)
1) AgOTf
2) NIS/TfOH
AcO
AcO
AcO
O
O
MBzO
O BnO
O
OAc
O
BzO OMe
143 (76%)
142 (2.0 eq)
Scheme 30. A branched OPG employing the combination of orthogonal donors (71/142) and distinguishable acceptors (6- vs. 3-OH on 141).
collaborators, in 2002, to a novel concept of reciprocal
donor-acceptor selectivity (RDAS) [62]. In a RDAS-based
OPG shown in Scheme 33, a 1 : 1.3 : 1.3 mixture of diol 163,
n-pentenyl donor 162, and n-pentenyl orthoester donor 161
was treated with NIS (2.5 eq)/BF3OEt2 (cat.), trisaccharide
164 and disaccharide 165 was obtained as the only products
in 37% and 37% yields, respectively. The results indicate a
reciprocal choice of donor 161 for the 3-OH and donor 162
for the 2-OH. However, a rational of these selectivities
awaits further insight.
CONCLUSION
The last decade has witnessed the advent to fully
development of the OPG procedures for the chemical
synthesis of oligosaccharides. The influence of the armeddisarmed protecting groups, together with other structural
192
Current Organic Chemistry, 2005, Vol. 9, No. 2
Yu and Cao
OBzM
HO
O
BnO
HO
OH
O
MBzO
MBzO
O
MBzO
MBzO
MBzO Br
SEt
AgOTf
O
BnO
BnO
AcO OMe
O
O
O BnO
O
O
O
MBzO
MBzO
BzO
PivO
O
MBzO
SPh
PivO
149 (6 eq)
148 (1.25 eq)
AgOTf/HfCp2Cl2
MBzO
BnO
BnO
BnO
OBn
O
SPh
147 (1.0 eq)
OBzM
O
MBzO
MBzO
HO
O
BzO
146 (1.8 eq)
MeOTf
DMTST
HO
BnO
HO
SEt
PivO
145 (1.1 eq)
144 (1.1 eq)
AcO
AcO
F
MBzO
71 (1.16 eq)
BzO
OBn
O
BnO
BnO
BnO
BnO
BnO
150 (24%)
O
O
BnO
O
O
BzO
AcO
AcO
PivO
O
AcO OMe
Scheme 31. A six-step OPG synthesis of the heptaglucan of the phytoalexin elicitor on a manual synthesizer.
TrO
BzO
BzO
O
O
OTr
TMSOTf
HO
O
BzO
BzO
CCl3
0 oC
O
-60 oC
+
NH
BzO O
155
OR
BzO
151
O
OBz
O
NH
BzO
BzO O
152
153 R = Tr
154 R = H
rt
O
CCl3
O
BzO
O
O
O
O
BzO
O
BzO
O
O
O
BzO
OBz
BzO
OBz
O AcO
TMSOTf/NIS
OBz
TrO
156
AcO
O
OBz
OBz
OAc
O
AcO
OBz
OBz
O
OBz
OAc
160 (62%)
NH
BzO
O
CCl3
O
TMSOTf
O
O
AcO
AcO
OAc
157
BzO
HO
AcO
SPh
158
OAc
O
AcO
O
AcO
OAc
SPh
AcO
OAc
159
Scheme 32. A two-flask hybrid OPG for the first synthesis of a bidesmosidic triterpene saponin.
factors, on the reactivity of glycosyl donors, are able to be
quantified, thus a reactivity-based OPG could be
programmable. The exploration of orthogonal leaving groups
and the distinguishable acceptors has brought additional
levels for sequential control of the OPG synthesis, thus
multi-step OPGs become common practice. Addition
sequence, temperature, solvent, as well as using separate
flasks then mixing, provide external control for the OPG
sequence. While the reciprocal donor-acceptor selectivity
(RDAS) awaits further insight. The six-step OPG synthesis
of the heptaglucan of phytoalexin elicitor on a manual
synthesizer represents a height has been reached, and
foresees the future trend, that the OPG procedure, which is
performed in solution phase, might be an alternative for
automation of the oligosaccharide synthesis, comparable to
the solid phase methods for peptide and nucleotide synthesis.
One-Pot Glycosylation (OPG) for the Chemical Synthesis of Oligosaccharides
Ph
[16]
O
O
BzO
BzO
BzO
Ph
O
O
HO
O
HO
OBn
[17]
[18]
[19]
O
O
161 (1.3 eq)
BnO
BnO
BnO
OMe
163 (1 eq)
O
NIS/BF3OEt2
[26]
OBn
BnO
BnO
BnO
O
Ph
O
O
[27]
OH
O
O
O
Ph
O
[28]
OMe
O
O
[29]
[30]
O
BzO
O
[32]
BzO
BzO
OBz
OBz
[31]
OM
e
O
BzO
[20]
[21]
[22]
[23]
[24]
[25]
O
162 (1.3 eq)
Current Organic Chemistry, 2005, Vol. 9, No. 2 193
164 (37%)
OBz
OBz
165 (37%)
[33]
[34]
[35]
[36]
Scheme 33. OPG using donors/acceptors with reciprocal
selectivity.
[37]
ACKKOWLEDGEMENT
B. Y. thanks the National Natural Science Foundation of
China (29925203) and the Chinese Academy of Sciences for
supporting his independent earlier career.
[38]
[39]
REFERENCES
[1]
[2]
[3]
[4]
[5]
[6]
[7]
[8]
[9]
[10]
[11]
[12]
[13]
[14]
[15]
Paulsen, H. Angew. Chem. Int. Ed. Engl. 1982, 21, 155.
Schmidt, R. R. Angew. Chem. Int. Ed. Engl. 1986, 25, 212.
Toshima, K.; Tatsuta, K. Chem. Rev. 1993, 93, 1503.
Boons, G.-J. Comtemp. Org. Synth. 1996, 173.
Seeberger, P. H.; Bilodeau, M. T.; Danishefsky, S. J. Aldrichimica
Acta, 1997, 30, 75.
Davis, B. G. J. Chem. Soc.; Perkin Trans 1 2000, 2137.
Nicolaou, K. C.; Mitchell, H. Angew. Chem. Int. Ed. 2001, 40,
1576.
Sears, P.; Wong, C. -H. Science, 2001, 291, 2344.
Raghavan, S.; Kahne, D. J. Am. Chem. Soc., 1993, 115, 1580.
Simanek, E. E.; Wong, C. -H. in Solid Support Oligosaccharide
Synthesis and Combinatorial Carbohydrate Libraries, Eds. by
Seeberger, P. H. John Wiley & Sons: New York, 2001, pp. 213.
Mootoo, D. R.; Konradsson, P.; Udodong, U.; Fraser-Reid, B. J.
Am. Chem. Soc. 1988, 110, 5583.
Fraser-Reid, B.; Wu, Z.; Udodong, U. E.; Ottosson, H. J. Org.
Chem. 1990, 55, 6068.
Veeneman, G. H.; van Boom, J. H. Tetrahedron Lett. 1990, 31,
275.
Friesen, R. W.; Danishefsky, S. J. Tetrahedron 1990, 46, 103.
Fraser-Reid, B.; Wu, Z.; Andrews, C. W.; Skowronski, E.; Bowen,
J. P. J. Am. Chem. Soc., 1991, 113, 1434. For recent example, see:
[40]
[41]
[42]
[43]
[44]
[45]
[46]
[47]
[48]
[49]
[50]
[51]
[52]
[53]
[54]
[55]
[56]
Jensen, H. H.; Nordstrøm, L. U.; Bols, M. J. Am. Chem. Soc. 2004,
126, 9205.
Nicolaou, K. C.; Dolle, R. E.; Papahatjis, D. P.; Randall, J. L. J.
Am. Chem. Soc., 1984, 106, 4189.
Kanie, O.; Ito, Y.; Ogawa, T. J. Am. Chem. Soc. 1994, 116, 12073.
Mehta, S.; Pinto, B. M. J. Org. Chem. 1993, 58, 3269.
Roy, R.; Andersson, F. O.; Letellier, M. Tetrahedron Lett. 1992,
33, 6053.
Kong, F. Curr. Org. Chem. 2003, 7, 841.
Boons, G. -J.; Bowers, S.; Coe, D. M. Tetrahedron Lett. 1997, 38,
3773.
Zhu, T.; Boons, G. -J. Tetrahedron Lett. 1998, 39, 2187.
Zhu, T.; Boons, G. -J. Angew. Chem., Int. Ed. 1998, 37, 1898.
Zhu, T.; Boons, G. -J. Angew. Chem. Int. Ed. 1999, 38, 3495.
Ley, S. V.; Priepke, H. W. M. Angew. Chem. Int. Ed. Engl. 1994,
33, 2292.
Lu, S. F.; O’yang. Q. Q.; Guo, Z. W.; Yu, B.; Hui, Y. Z. Angew.
Chem., Int. Ed. Engl. 1997, 36, 2344.
Yoshida, M.; Kiyoi, T.; Tsukida, T.; Kondo, H. J. Carbohydr.
Chem. 1998, 17, 673.
Zhang, Z.; Ollmann, I. R.; Ye, X. -S.; Wischnat, R.; Baasov, T.;
Wong, C. -H. J. Am. Chem. Soc. 1999, 121, 734.
Ye, X. -S.; Wong, C. -H. J. Org. Chem. 2000, 65, 2410.
Burkhart, F.; Zhang, Z.; Wacowich-Sgarbi, S.; Wong, C. -H.
Angew. Chem. Int. Ed. 2001, 40, 1274.
Mong, K. -K. T.; Wong, C. -H. Angew. Chem. Int. Ed. 2002, 41,
4087.
Zhang, Z.; Niikura, K.; Huang, X. -F.; Wong, C. -H. Can. J. Chem.
2002, 80, 1051.
Mong, T. K.-K.; Huang, C. -Y.; Wong, C. -H. J. Org. Chem. 2003,
68, 2135.
Lahmann, M.; Oscarson, S. Org. Lett. 2000, 2, 3881.
Fridman, M.; Solomon, D.; Yogev, S.; Baasov, T. Org. Lett. 2002,
4, 281.
Jona, H.; Takeuchi, K.; Saitoh, T.; Mukaiyama, T. Chem. Lett.
2000, 1178.
Green, L.; Hinzen, B.; Ince, S. J.; Langer, P.; Ley, S. V.; Warriner,
S. L. Synlett. 1998, 440.
Chiba, H.; Mukaiyama, T. Chem. Lett., 2003, 32, 172.
Yamada, H.; Harada, T.; Miyazaki, H.; Takahashi, T. Tetrahedron
Lett. 1994, 35, 3979.
Yamada, H.; Harada, T.; Takahashi, T. J. Am. Chem. Soc. 1994,
116, 7919.
Chenault, H. K.; Castro, A. Tetrahedron Lett. 1994, 35, 9145.
Grice, P.; Ley, S. V.; Pietruszka, J.; Priepke, H. W. M.; Walther, E.
P. E. Synlett. 1995, 781.
Yu, B.; Yu, H.; Hui, Y.; Han, X. Tetrahedron Lett. 1999, 40, 8591.
Yu, H.; Yu, B.; Wu, X.; Hui, Y.; Han, X. J. Chem. Soc., Perkin
Trans. 1, 2000, 1445.
Mukaiyama, T.; Wakiyama, Y.; Miyazaki, K.; Takeuchi, K. Chem.
Lett. 1999, 933.
Takeuchi, K.; Tamura, T.; Mukaiyama, T. Chem. Lett., 2000, 124.
Jona, H.; Takeuchi, K.; Mukaiyama, T. Chem. Lett., 2000, 1278.
Mukaiyama, T.; Ikegai, K.; Jona, H.; Hashihayata, T.; Takeuchi, K.
Chem. Lett. 2001, 840.
Boons, G. -J.; Zhu, T. Synlett 1997, 809.
Valverde, S.; Garcia, M.; Gomez, A. M.; Lopez, J. C. Chem.
Commun. 2000, 813.
Wang, H.; Ning, J. J. Org. Chem. 2003, 68, 2521.
Cheung, M. -K.; Douglas, N. L.; Hinzen, B.; Ley, S. V.;
Pannecoucke, X. Synlett 1997, 257.
Grice, P.; Ley, S. V.; Pietruszka, J.; Osborn, H. M. I.; Priepke, H.
W. M.; Warriner, S. L. Chem. Eur. J. 1997, 3, 431.
Douglas, N. L.; Ley, S. V.; Lucking, U.; Warriner, S. L. J. Chem.
Soc. Perkin Trans. 1, 1998, 51
Baeschlin, D. K.; Green, L. G.; Hahn, M. G.; Hinzen, B.; Ince, S.
J.; Ley, S. V. Tetrahedron: Asymmetry 2000, 11, 173.
Yamada, H.; Kato, T.; Takahashi, T. Tetrahedron Lett.1999, 40,
4581.
194
[57]
[58]
[59]
Current Organic Chemistry, 2005, Vol. 9, No. 2
Takahashi, T.; Adachi, M.; Matsuda, A.; Doi, T. Tetrahedron Lett.
2000, 41, 2599.
Yamada, H.; Takimoto, H.; Ikeda, T.; Tsukamoto, H.; Harada, T.;
Takahashi, T. Synlett 2001, 1751.
Tanaka, H.; Adachi, M.; Tsukamoto, H.; Ikeda, T.; Yamada, H.;
Takahashi, T. Org. Lett. 2002, 4, 4213.
Yu and Cao
[60]
[61]
[62]
Mukaiyama, T.; Ikegai, K.; Hashihayata, T.; Kiyota, K.; Jona, H.
Chem. Lett. 2002, 730.
Yu, B.; Xie, J. M.; Deng, S; Hui, Y. J. Am. Chem. Soc. 1999, 121,
12196.
Fraser-Reid, B.; Lopez, J. C.; Radhakrishnan, K. V.; Nandakumar,
M. V.; Gomez, A. M.; Uriel, C. Chem. Commun. 2002, 2104.