Regio- and stereoselective β-mannosylation using a boronic acid catalyst and its application in the synthesis of a tetrasaccharide repeating unit of lipopolysaccharide derived from E. coli O75

Article abstract of DOI:10.1039/c7cc00269f

Regio- and stereoselective β-mannosylations using 1,2-anhydromannose and diol sugar acceptors in the presence of a boronic acid catalyst proceeded smoothly to give the corresponding β-mannosides with high regio- and β-stereoselectivities in high yields without further additives under mild conditions. In addition, this glycosylation method was applied successfully to the synthesis of a tetrasaccharide repeating unit of lipopolysaccharide (LPS) derived from E. coli O75.

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Regioꢀ and stereoselective βꢀmannosylation using a boronic acid catalyst
and its application to the synthesis of a tetrasaccharide repeating unit of
lipopolysaccharide derived from E. coli O75
Nobuya Nishi, Junki Nashida, Eisuke Kaji, Daisuke Takahashi* and Kazunobu Toshima*
5
Received (in XXX, XXX) Xth XXXXXXXXX 20XX, Accepted Xth XXXXXXXXX 20XX
DOI: 10.1039/b000000x
Regioꢀ and stereoselective βꢀmannosylations using 1,2ꢀ
anhydromannose and diol sugar acceptors in the presence of
a boronic acid catalyst proceeded smoothly to give the
10 corresponding βꢀmannosides with high regioꢀ and
β−stereoselectivities in high yields without further additives
under mild conditions. In addition, this glycosylation method
was applied successfully to the synthesis of a tetrasaccharide
repeating unit of lipopolysaccharide (LPS) derived from E.
15 coli O75.
45
50
One of the most challenging aspects of oligosaccharide
synthesis is establishing the regioꢀ and α/βꢀstereoselectivity of
the glycosidic linkages. For α/βꢀstereoselectivity, a method based
on neighboringꢀgroup participation from a 2ꢀOꢀacyl functionality
20 in the glycosyl donor is most promising for providing 1,2ꢀtransꢀ
glycosides. However, the stereoselective synthesis of 1,2ꢀcisꢀ
glycosides, especially βꢀmannosides, remains difficult due to the
nonꢀavailability of neighboringꢀgroup participation and both
anomeric and steric effects of the axial substituent at the C2
25 position.1 To overcome these obstacles, efforts have been made to
develop efficient methods, including direct βꢀmannosylation
using silver salts with mannosyl halides as glycosyl donors,2
inversion of the C2 configuration of βꢀglucosides,3 intramolecular
aglycon delivery (IAD),4 anomeric Oꢀalkylations,5 use of 4,6ꢀOꢀ
30 benzylideneꢀ,6 4,6ꢀOꢀarylboronateꢀ7 or 4,6ꢀOꢀsilyleneꢀ8 protected
mannosyl donors, hydrogenꢀmediated aglycon delivery (HAD)
with 3ꢀ and/or 6ꢀOꢀpicoloyl mannosyl donors,9 use of a glycosylꢀ
acceptorꢀderived borinic ester catalyst with 1,2ꢀanhydromannose
donor,10 and use of 2,6ꢀ11 or 3,6ꢀlactone mannosyl donors.12 For
35 regioselectivity, efficient approaches using organotin13 or
organoboron reagents14ꢀ16 have been developed; however, most of
the glycosylations were regioꢀ and 1,2ꢀtransꢀselective, and few
were regioꢀ and 1,2ꢀcisꢀselective.
Scheme 1 Regioꢀ and stereoselective (A) αꢀglucosylation and (B) βꢀ
mannosylation using a glycosylꢀacceptorꢀderived boronic ester.
55 glycosyl acceptors in the presence of the corresponding glycosylꢀ
acceptorꢀderived boronic ester catalyst 2 have been recently
reported.17
In the present study, the reactions proceeded smoothly to
provide the corresponding αꢀglucoside 4 with high regioꢀ and
60 stereoselectivities in high yield under mild conditions (Scheme
1A). Based on previous work, the boronic ester 2 was expected to
act as an activator of 1,2ꢀanhydromannose 518 to generate βꢀ
mannoside 7 with high regioꢀ and stereoselectivities (Scheme 1B).
This report describes a novel regioꢀ and stereoselective βꢀ
65 mannosylation of 5 and a diol glycosyl acceptor utilizing a
boronic acid catalyst and its application to the synthesis of a
tetrasaccharide repeating unit of LPS derived from E. coli O75.
Initial investigation led to the selection of 1,2ꢀanhydromannose
5 and 4ꢀmethoxyphenylboronic acid (8a), phenylboronic acid
70 (8b), 4ꢀfluorophenylboronic acid (8c), and 4ꢀnitrophenylboronic
acid (8d) as the glycosyl donor and arylboronic acids,
respectively. First, glycosylation of 5 and the 1,3ꢀdiol sugar
acceptor, glucoside 9, was attempted using catalytic amounts of
the glycosylꢀacceptorꢀderived boronic esters 10a−d, which were
75 prepared by mixing 9 and catalytic amounts of 8a−d in refluxing
toluene, followed by concentration in vacuo, respectively, under
different reaction conditions. The results indicated that
glycosylation of 5 and 9 using 8a, which possesses an electronꢀ
donating methoxy group, in MeCN at 25 °C for 6 h proceeded to
80 give (1,6) mannoside 11 in 43% yield with a 51:49 β/α ratio as a
single regioisomer (Table 1, entry 1).19 To improve the βꢀ
In this context, regioꢀ and 1,2ꢀcisꢀαꢀstereoselective
40 glycosylations using 1,2ꢀanhydroglucose donor 1 and diol
Department of Applied Chemistry, Faculty of Science and Technology,
Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama 223-8522
(Japan). E-mail: dtak@applc.keio.ac.jp, toshima@applc.keio.ac.jp;
Fax: (+81) 45-566-1576.
† Electronic supplementary information (ESI) available: See
DOI: 10.1039/b000000x/
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Table 1 Glycosylations of 5 and 9 using glycosylꢀacceptorꢀderived
boronic ester catalysts 10a−d under different reaction conditions.
45
5
50
Fig. 1 Electrostatic effect of the substituents on the benzene ring in 10a
55 and 10d during glycosylation of 5 and 9.
10
yield of 12 (Table 1, entries 5 and 6). The solvent effect was also
examined using THF, CH2Cl2, and toluene. The results indicated
that only MeCN gave complete βꢀstereoselectivity for the
glycosylation reaction (Table 1, entries 6–9). Thus, glycosylaton
60 of 5 and 9 using 10d in MeCN at −20 oC for 6 h provided the best
outcome, producing 11β in 90% yield as a single isomer (Table 1,
entry 6). In addition, when the glycosylation of 5 and 9 using 8d
without preꢀformation of 10d was examined, almost the same
result was obtained (85% yield as a single isomer). This result
65 indicated that preꢀformation of 10d was not necessary for this
glycosylation reaction.
entry boronic temp
solvent
yield of 11
β/α ratio
of 11
yield of 12
acid
(°C)
(%)
(%)
1
2
3
4
5
6
7
8
9
8a
8b
8c
25
25
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
THF
43
69
72
79
87
90
81
46
56
51/49
83/17
92/8
0
0
25
0
8d
8d
8d
8d
8d
8d
25
β only
β only
β only
94/6
10
trace
0
0
−20
−20
−20
−20
0
Next, the regioselectivity and applicability of this
glycosylation method was examined using several 1,3ꢀdiol sugar
acceptors (13ꢀ16; Scheme 2). The use of mannoside 13 and glucal
70 14 as glycosyl acceptors in the presence of 8d provided excellent
regioꢀ and βꢀstereoselectivities, and produced only the
corresponding β(1,6) mannosides 17 and 18 as single isomers in
81% and 91% yields, respectively (Schemes 2A and 2B).19 In
addition, when glucosaminide 15 was employed for glycosylation
75 using 8d, the corresponding regioisomer β(1,4) mannoside was
obtained in 4% yield, but high regioselectivity and excellent βꢀ
stereoselectivity were observed, and the β(1,6) mannoside 19 was
obtained in high yield (Scheme 2C).19 Interestingly, when
galactoside 16 was employed under the same reaction conditions,
80 excellent regioꢀ and βꢀstereoselectivities were observed, and only
glycosylation at the axial 4ꢀOH proceeded to give the β(1,4)
mannoside 20 as a single isomer in high yield (Scheme 2D).19
The high regioselectivity observed may be due to the proposed
(A)
CH2Cl2
toluene
43/57
52/48
0
0
stereoselectivity, the electrostatic effect of substituents on the
benzene ring in the boronic acids was investigated using 8bꢀd.
When 8b with no substituent or 8c with an electronꢀwithdrawing
15 fluorine group was used, both the chemical yield and βꢀ
stereoselectivity of 11 increased significantly (Table 1, entries 2
and 3). Furthermore, when 8d with a strong electronꢀwithdrawing
nitro group was used, β(1,6) mannoside 11β was obtained as a
single isomer in 79% yield, along with trisaccharide 12 in 10%
20 yield as an overreaction byproduct20 (Table 1, entry 4). The
anomeric configurations of 11α and 11β were determined from
their 1JCH coupling constants, 168 and 158 Hz, respectively.21 The
results suggest that the electronꢀdonating group in 10a reduces
the Lewis acidity of the boron atom, causing weak activation of 5
25 by 10a, and intermolecular SN2 type substitution of 9 from the αꢀ
face of 5. However, the electronꢀwithdrawing group in 10d
increases the Lewis acidity of the boron atom, which causes
activation of 5 by 10d, formation of the oxonium cation, and SN1
type intramolecular nucleophilic attack of the boronꢀbound
30 oxygen atom in the boronate ester from the same βꢀface of the
oxonium cation (Fig. 1). The high regioselectivity observed can
be explained through the following proposed transition state
models. During glycosylation of 5 and 9 using 10d, compound 5
approaches from the equatorial face of the boron atom in 10d to
35 minimize steric hindrance, and generates the oxonium cation
involving the boronate ester. At this stage, since significant steric
hindrance between the anomeric proton of the oxonium cation
and the benzene ring of the boronate ester destabilizes the TSꢀ1
transition state, glycosylation by the oxygen atom at the 6ꢀ
40 position occurs through the favored TSꢀ2 to give 11β (Fig. 2A).
Next, the reaction temperature and solvent were optimized for
glycosylation of 5 and 9. When the glycosylations were
conducted at 0 °C and −20 °C, the chemical yields of 11β
increased to 87% and 90%, respectively, because of the decreased
BnO
BnO
BnO
HO
HO
BzO
8d
OH
OBz
O
O
(0.2 equiv.)
85
O
OBz
5
+
O
MeCN, 0 o
8 h
C
HO
(3.0 equiv.)
BzO
OMe
17: 81%
(1,6) only
13(1.0 equiv.)
OMe
(B)
BnO
8d
OH
OH
O
(0.2 equiv.)
BnO
BnO
O
5
+
+
O
HO
BzO
90
MeCN, -20 o
6 h
C
(3.0 equiv.)
O
HO
BzO
18: 91%
(1,6) only
14(1.0 equiv.)
BnO
BnO
BnO
(C)
8d
OH
HO
HO
O
(0.2 equiv.)
O
O
5
OMe
BzO
MeCN, 0 o
12 h
C
(3.0 equiv.)
O
HO
BzO
OMe
AcHN
95
19: 78%
(1,4) isomer: 4%
AcHN
15(1.0 equiv.)
OH
HO
BnO
OH
8d
(D)
OH
O
O
(0.2 equiv.)
BnO
O
O
5
+
BnO
OMe
MeCN, 0 o
12 h
C
BzO
(3.0 equiv.)
OMe
BzO
16(1.0 equiv.)
BzO
20: 86%
BzO
100
(1,4) only
Scheme 2 Glycosylation of 5 and the 1,3ꢀdiol sugar acceptors 13ꢀ16
using 8d.
2
|
Journal Name, [year], [vol], 00–00
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DOI: 10.1039/C7CC00269F
60
65
70
5
10
15 Fig. 2 Proposed rationale for the regioselectivity in the glycosylation of
(A) 5 and 9, and (B) 5 and 16.
transition state models TSꢀ3 and TSꢀ4 shown in Fig. 2B. Thus, in
the glycosylation of 5 and 16 using 8d, steric hindrance between
the anomeric proton of the oxonium cation and the benzene ring
20 of the boronate ester destabilized TSꢀ3. Therefore, 20 was
regioselectively obtained through the favored TSꢀ4. In addition,
these results interestingly indicate that the observed
regioselectivities in the glycosylations were completely opposite
to those in the previously reported glycosylations using 1,2ꢀ
25 anhydroglucose donor.17
To investigate further the generality of this present method, we
next examined the glycosylations of 5 with cisꢀ1,2ꢀdiol sugar
acceptors, that is the mannoside 21 and galactoside 22. When the
glycosylation of 5 and 21 using 8d was conducted, the β(1,3)
30 glycoside 23 was obtained in 75% yield as a single isomer with
excellent βꢀstereoselectivity (Scheme 3A).19 When the
glycosylation of 5 and 22 in the presence of 8d was conducted, it
was found that the glycosylation also proceeded smoothly to give
24 in 71% yield with high βꢀstereoselectivity (β/α = 92/8) along
35 with minor β(1,4) isomer in 21% yield (Scheme 3B).19 These
results indicate that although the regioselectivity in the
glycosylation of 5 and 22 was moderate, cisꢀ1,2ꢀdiol acceptors
also can be applied for the present glycosylation method.
75 Scheme 4 Retrosynthetic analysis of the tetrasaccharide 25.
Misra et al. reported the synthesis of the tetrasaccharide structure
as its 4ꢀmethoxyphenyl (PMP) glycoside, they used the inversion
method of the C2 configuration of the βꢀglucoside.23 The
retrosynthetic analysis of 25 is shown in Scheme 4. Compound
80 25 could be synthesized by the present regioꢀ and stereoselective
βꢀmannosylation of 5 and trisaccharide 26 using 8d as a catalyst,
followed by deprotection reactions. The trisaccharide 26 could be
prepared by regioselective glycosylation of 27 and 28 using 8a as
a transient masking group16 of the 1,3ꢀdiol in 28. αꢀGalactoside
85 28 would be prepared by 1,2ꢀcisꢀαꢀstereoselective glycosylation24
of 29 and octanol (31) using a bis(4ꢀfluorophenyl)borinic acid
(30).
The synthetic scheme for 25 is summarized in Scheme 5. First,
the αꢀgalactoside 32 was synthesized through αꢀstereoselective
90 glycosylation of 1,2ꢀanhydrogalactose 29 and octanol (31) using
a catalytic amount of 30 in THF at 0 °C for 24 h, producing the
desired αꢀgalactoside 32 in 74% yield with excellent αꢀ
stereoselectivity. The anomeric configuration of 32 was
determined by a coupling constant, J1,2 = 4.0 Hz. Compound 32
95 was converted into the triol acceptor 28 by benzoylation and
debenzylation. Next, glycosylation of 27 and 28 was examined
using a stochiometric amount of 8a as a transient masking group
of the 1,3ꢀdiol. After mixing 28 and 8a in acetone at reflux for 2 h,
followed by concentration in vacuo to form boronic ester 33,
100 glycosylation of 27 (synthetic scheme is shown in the ESI) in the
presence of MS 4 Å in DCE/toluene at −30 °C for 3 h was
conducted. The glycosylation proceeded smoothly to give β(1,3)
glycoside 26 (J1,2 = 8.5 Hz) in 96% yield with complete
regioselectivity.19 Next, glycosylation of 26 and 5 was conducted
105 using a catalytic amount of 8d in MeCN at 0 °C for 24 h, which
40
45
resulted in 91% yield of the desired β(1,4) mannoside 34 (1JCH
=
Scheme 3 Glycosylation of 5 and the cisꢀ1,2ꢀdiol sugar acceptors 21 and
50 22 using 8d.
161 Hz)21 with complete regioꢀ and βꢀstereoselectivity.19 These
results demonstrate the high efficiency and generality of the
present glycosylation method. In addition, removal of benzoyl
110 and phthaloyl groups, followed by acetylation gave 35. Finally,
deprotection of the benzyl and acetyl groups in 35 furnished the
desired tetrasaccharide 25.
Finally, the present glycosylation method was applied to the
synthesis of the octyl tetrasaccharide glycoside 25. The
tetrasaccharide structure in 25 was reported by Erbing and coꢀ
workers22 as a repeating unit of Oꢀspecific sideꢀchains of LPS
55 derived from E. coli O75. Structurally, the main difficulty in the
synthesis of the tetrasaccharide is direct and stereoselective
construction of β(1,4) mannosidic linkage. In 2012, although
In conclusion, the first regioꢀ and stereoselective βꢀ
mannosylation were developed utilizing a boronic acid catalyst
115 without any further additives under mild reaction conditions. The
This journal is © The Royal Society of Chemistry [year]
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DOI: 10.1039/C7CC00269F
Stork and G. Kim, J. Am. Chem. Soc., 1992, 114, 1087; (d) Y. Ito and
T. Ogawa, Angew. Chem., Int. Ed. Engl., 1994, 33, 1765.
(a) R. R. Schmidt, U. Moering and M. Reichrath, Chem. Ber., 1982,
115, 39; (b) J. Tamura and R. R. Schmidt, J. Carbohydr. Chem., 1995,
14, 895; (c) G. Hodosi and P. Kováč, J. Am. Chem. Soc., 1997, 119,
2335; (d) H. Nguyen, D. Zhu, X. Li and J. Zhu, Angew. Chem., Int.
Ed., 2016, 55, 4767.
(a) D. Crich and S. Sun, J. Am. Chem. Soc., 1998, 120, 435; (b) R.
Weingart and R. R. Schmidt, Tetrahedron Lett., 2000, 41, 8753; (c)
K. S. Kim, J. H. Kim, Y. J. Lee, Y. J. Lee and J. Park, J. Am. Chem.
Soc., 2001, 123, 8477; (d) D. Crich and M. Smith, J. Am. Chem. Soc.,
2001, 123, 9015; (e) T. Tsuda, S. Sato, S. Nakamura and S.
Hashimoto, Heterocycles, 2003, 59, 509; (f) S. Tanaka, M. Takashina,
H. Tokimoto, Y. Fujimoto, K. Tanaka and K. Fukase, Synlett, 2005,
2325; (g) K. S. Kim, D. B. Fulse, J. Y. Baek, B.ꢀY. Lee and H. B.
Jeon, J. Am. Chem. Soc., 2008, 130, 8537; (h) P. Sun, P. Wang, Y.
Zhang, X. Zhang, C. Wang, S. Liu, J. Lu and M. Li, J. Org. Chem.,
2015, 80, 4164.
F
B OH
BnO
BnO
2
1. BzCl (3.0 equiv.)
py, rt, 18 h, 90%
OBn
O
BnO
BnO
5
6
OBn
O
30 (0.2 eq.)
HO
OC8H17
2. Pd(OH)2/C (100 wt%)
H2 (1.0 atm), THF
rt, 30 min, 98%
31
octanol ( ) (1.0 equiv.)
THF, 0 °C, 24 h
74% (
115
120
O
5
29 (2.0 equiv.)
32
= >95/5)
BnO
O
HO
SEt
O
NPhth
Ar
O
BnO
B
HO
O
OH
O
BnO
27
(2.0 equiv.)
O
8a
(1.05 equiv.)
OBn
O
HO
10
HO
acetone
NIS (2.4 equiv.), TfOH (0.2 equiv.)
DCE/toluene = 1/1
BzO
BzO
reflux, 2 h
OC8H17
OC8H17
Å
MS 4 (100 wt%)
28
33
-30 °C, 3 h, 96%, (1,3) only
125
130
135
5
(3.0 equiv.)
BnO
OH
O
8d (0.2 equiv.)
MeCN, 0 °C
BnO
O
HO
OH
O
BnO
HO
O
OH
BnO
15
O
O
BnO
O
NPhth
O
O
7
8
D. Crich and M. Smith, J. Am. Chem. Soc., 2002, 124, 8867.
M. Heuckendorff, J. Bendix, C. M. Pedersen and M. Bols, Org. Lett.,
2014, 16, 1116.
S. G. Pistorio, J. P. Yasomanee and A. V. Demchenko, Org. Lett.,
2014, 16, 716.
HO
24 h, 91%
(1,4) only
BzO
O
BzO
O
OC8H17
BnO
NPhth
OC8H17
O
BnO
26
34
BnO
OBn
BnO
9
OBn
1. NaOMe, MeOH
rt. to 40 °C, 10 h
2. ethylenediamine
BnO
OAc
O
10 M. Tanaka, J. Nashida, D. Takahashi and K. Toshima, Org. Lett.,
2016, 18, 2288.
11 Y. Hashimoto, S. Tanikawa, R. Saito and K. Sasaki, J. Am. Chem.
Soc., 2016, 138, 14840.
12 H. Elferink, R. A. Mensink, P. B. White and T. J. Boltje, Angew.
Chem., Int. Ed., 2016, 55, 11217.
20
1. Pd(OH)2/C (100 wt%)
H2 (1.0 atm), THF
rt., 40 min
BnO
O
OAc
O
BnO
BnO
n-BuOH, reflux, 12 h
O
O
AcO
25
O
AcO
OC8H17
NHAc
35
2. NaOMe, MeOH
rt., 2 h
93% in 2 steps
O
BnO
3. Ac2O, DMAP, py
rt., 4 h, 95%
BnO
99% in 2 steps
OBn
140 13 (a) T. Ogawa, K. Katano and M. Matsui, Carbohydr. Res., 1978, 64,
C3; (b) C. Cruzado, M. Bernabe and M. MartinꢀLomas, Carbohydr.
Res., 1990, 203, 296; (c) P. J. Garegg, J.ꢀL. Maloisel and S.
Oscarson, Synthesis 1995, 409; (d) E. Kaji, N. Harita, Tetrahedron
Lett., 2000, 41, 53; (e) E. Kaji, K. Shibayama and K. In, Tetrahedron
25
Scheme 5 Synthetic scheme for tetrasaccharide 25.25
use of 1,2ꢀanhydromannose donor 5 and 4ꢀnitrophenylboronic
acid (8d) in MeCN was effective for the glycosylations with
several diol acceptors. Furthermore, this glycosylation method
145
150
155
160
165
170
Lett., 2003, 44, 4881; (f) W. Muramatsu and H. Yoshimatsu, Adv.
Synth. Catal., 2013, 355, 2518.
14 For a recent review, see: C. A. McClary and M. S. Taylor, Carbohydr.
Res., 2013, 381, 112;
30 was applied successfully to the synthesis of the tetrasaccharide
repeating unit of LPS derived from E. coli O75. Therefore, we
anticipate that this method will be widely applicable to the other
types of donors, such as the 1,2ꢀanhydromannose donors
protected with ester protecting groups, and the acceptors for the
35 synthesis of the other compounds. These applications and
detailed mechanistic studies of this method are now underway.
15 For examples of regioselective glycosylation with a coordinated
organoboron promoter, see: (a) K. Oshima and Y. Aoyama, J. Am.
Chem. Soc., 1999, 121, 2315; (b) C. Gouliaras, D. Lee, L. Chan and
M. S. Taylor, J. Am. Chem. Soc., 2011, 133, 13926; (c) S. O. Bajaj, E.
U. Sharif, N. G. Akhmedov and G. A. O’Doherty, Chem. Sci., 2014,
5, 2230; (d) T. M. Beale, P. J. Moon and M. S. Taylor, Org. Lett.,
2014, 16, 3604; (e) K. A. D’Angelo and M. S. Taylor, J. Am. Chem.
Soc., 2016, 138, 11058.
16 For examples of regioselective glycosylation with an aryboronic acid
as a transient masking group, see: (a) E. Kaji, T. Nishino, K. Ishige,
Y. Ohya and Y. Shirai, Tetrahedron Lett., 2010, 51, 1570; (b) T.
Nishino, Y. Ohya, R. Murai, T. Shirahata, D. Yamamoto, K. Makino
and E. Kaji, Heterocycles, 2012, 84, 1123; (c) M. Nakanishi, D.
Takahashi and K. Toshima, Org. Biomol. Chem., 2013, 11, 5079; (d)
T. H. Fenger and R. Madsen, Eur. J. Org. Chem., 2013, 5923; (e) E.
Kaji, D. Yamamoto, Y. Shirai, K. Ishige, Y. Arai, T. Shirahata, K.
Makino and T. Nishino, Eur. J. Org. Chem., 2014, 3536.
This research was supported in part by the MEXTꢀsupported
Program for the Strategic Research Foundation at Private
40 Universities, 2012ꢀ2016, and JSPS KAKENHI Grant Numbers
JP16H01161 in Middle Molecular Strategy and JP16K05781.
Notes and references
1
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17 A. Nakagawa, M. Tanaka, S. Hanamura, D. Takahashi and K.
Toshima, Angew. Chem., Int. Ed., 2015, 54, 10935.
45
2
(a) P. A. J. Gorin and A. S. Perlin, Can. J. Chem., 1961, 39, 2474; (b)
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3102.
18 S. Manabe, Y. Marui and Y. Ito, Chem. Eur. J., 2003, 9, 1435.
19 The glycosidic linkage of the obtained glycoside was confirmed by
1
acetylation or benzoylation, and subsequent H NMR analysis of the
corresponding acetylated or benzoylated glycoside, respectively. see
the ESI.
20 A similar type of overreaction byproduct was obtained in our
previous study, see: ref. 17.
3
(a) O. Theander, Acta Chem. Scand., 1958, 12, 1883; (b) G. Ekborg,
B. Lindberg and J. Lonngren, Acta Chem. Scand. Ser. B, 1972, 26,
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175 21 K. Bock and C. Pedersen, J. Chem. Soc., Perkin Trans. 2, 1974, 293.
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23 A. Sau and A. K. Misra, PLoS ONE, 2012, 7, e37291.
24 M. Tanaka, D. Takahashi and K. Toshima, Org. Lett., 2016, 18, 5030.
180 25 Each synthetic step was repeated at least twice to confirm the
reproducibility.
105
110
4
For a selected review, see: (a) A. Ishiwata, Y. J. Lee and Y. Ito, Org.
Biomol. Chem., 2010, 8, 3596; For selected examples, see: (b) F.
Barresi and O. Hindsgaul, J. Am. Chem. Soc., 1991, 113, 9376; (c) G.
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