Catalytic and β-stereoselective mannosylation of several glycosyl acceptors with mannosyl 6-nitro-2-benzothiazoate

Article abstract of DOI:10.1246/cl.2003.442

Mannosylation of several glycosyl acceptors with a novel mannosyl donor having the 6-nitro-2-benzothiazoate function at an anomeric position proceeded smoothly in the presence of a catalytic amount of tetrakis(pentafluorophenyl)boric acid [HB(C₆

Full text of DOI:10.1246/cl.2003.442

442
Chemistry Letters Vol.32, No.5 (2003)
Catalytic and ꢀ-Stereoselective Mannosylation of Several Glycosyl Acceptors
with Mannosyl 6-Nitro-2-benzothiazoate
Takashi Hashihayata,y;yy Hiroki Mandai,y;yy and Teruaki MukaiyamaÃy;yy
yCenter for Basic Research, The Kitasato Institute (TCI), 6-15-5 Toshima, Kita-ku, Tokyo 114-0003
yyThe Kitasato Institute for Life Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641
(Received February 17, 2003; CL-030133)
Mannosylation of several glycosyl acceptors with a novel
Table 1. Mannosylation using various activators
mannosyl donor having the 6-nitro-2-benzothiazoate function
at an anomeric position proceeded smoothly in the presence
of a catalytic amount of tetrakis(pentafluorophenyl)boric acid
[HB(C6F5)4] to afford the corresponding disaccharides in high
yields with good to high ꢀ-stereoselectivities.
HO
BnO
O
BnO
BnO
BnO
BnO
BnO
BnO
BnO
BnO
BnO
O
O
BnO
OMe
2 (1.0 equiv.)
Activator
O
O
O
N
BnO
BnO
S
MS 5A (3 g/mmol)
2 CH2Cl2, −78 °C, 0.5 h
BnO
OMe
1 (1.2 equiv.)
3
NO
ꢀ-Mannopyranosyl units are the essential constituents of
naturally-occurring biologically active oligosaccharides and
glycoconjugates.1 Generally, formation of ꢀ-mannopyranoside
is rather difficult by chemical synthesis owing to the following
three factors: i) ꢁ-mannopyranoside formation is favored by its
anomeric effect; ii) steric repulsion of hydroxyl group at C-2
position; and iii) opposite participation of neighboring group.
Of the methods reported, the catalytic or stoichiometric direct
mannosylation2{9 was shown to be most effective for the conve-
nient construction of ꢀ-mannopyranoside, and the reactions
using mannosyl compounds such as mannosyl phos-
phinothioate,2 phosphate,3 halides,4;5 or sulfoxide5 together
with their suitable activators, and a donor having 1,2-stannylene
acetal6 were thus reported. Further, the best results were given
when donors having electron-withdrawing protecting group at
O-2 position7 or cyclic acetal protecting group at O-4,6
position8 were promoted by activators such as trifluoromethane-
sulfonates. To develop a convenient method for the stereoselec-
tive synthesis of ꢀ-mannopyranosides is still one of the most
important and challenging topics in carbohydrate chemistry.
Highly ꢀ-stereoselective glucosylations by using a novel gluco-
syl donor, ꢁ-glucosyl 6-nitro-2-benzothiazoate was recently
achieved by our research group.10 The donor reacted smoothly
with glycosyl acceptors in the presence of trifluoromethanesul-
fonic acid (TfOH) in CH2Cl2 to afford the corresponding ꢀ-glu-
cosides in high yields. It was noted that ꢀ-saccharide was ob-
tained more dominantly by the present method compared with
the similar glucosylation reactions which used other ꢁ-glucosyl
donors such as glucosyl thioform- and trichloroacet-imidates.
These results imply that the glycosyl benzothiazoate has a po-
tent and characteristic feature of forming ꢀ-saccharide. In this
communication, we would like to report on a direct ꢀ-stereose-
lective mannosylation of several glycosyl acceptors using a
newly devised donor, ꢁ-mannosyl 6-nitro-2-benzothiazoate.
2,3,4,6-Tetra-O-benzyl-ꢁ-D-mannopyranosyl 6-nitro-2-
benzothiazoate (1) was prepared easily according to the fol-
lowing procedure. The direct condensation reaction between
anomeric hydroxyl group of 2,3,4,6-tetra-O-benzyl-ꢁ,ꢀ-D-
mannopyranose and 2-chloro-6-nitrobenzothiazole pro-
ceeded smoothly to give ꢁ-isomer 1 and ꢀ-one in 66%
and 24% chemical yields, respectively, in the presence of
d
Entry
Activator (mol% based on acceptor)
Yield /% (
α
/
β
)
.
BF3 OEt2 (120)
70 (78/22)
97e (34/66)
95 (25/75)
1
2
TrB(C6F5)4 (120)
TMSOTf (120)
3
HClO4 (20)a
TfOH (20)
HNTf2 (20)b
HSbF6 (20)b
HB(C6F5)4 (20)c
89 (45/55)
99 (27/73)
92 (43/57)
4
5
6
90 (44/56)
7
8
96 (16/84)
aProtic acid was genarated from silver salt and tBuCl in toluene, and
the supernatant was used. bProtic acid was generated from silver salt
and tBuBr in toluene, and the supernatant was used. cProtic acid was
generated from silver salt and tBuBr in toluene - diethyl ether (1:1),
and the supernatant was used. dThe
α/β ratios were determined by
isolations of both stereoisomers. eThe reaction was carried out for 1 h.
potassium bis(trimethylsilyl)amide.
In the first place, the effect of various activators on the
mannosylation of methyl 2,3,4-tri-O-benzyl-a-D-glucopyrano-
side (2) with 1 in CH2Cl2 was examined (Table 1). In most
cases, the reactions smoothly proceeded at À78 ꢀC to give
the corresponding disaccharides 3 in high yields. It was in-
teresting to note that the mannosylation that used activators
having triflate or tetrakis(pentafluorophenyl)borate anion
gave disaccharides with high ꢀ-stereoselectivities (Entries
2, 3, 5, 8). The highest ꢀ-stereoselectivity was achieved
when tetrakis(pentafluorophenyl)boric acid11 [HB(C6F5)4]
was employed (Entry 8, ꢁ=ꢀ ¼ 14=86) while BF3ꢁEt2O, a
weaker Lewis acid, showed a reversed stereoselectivity
(Entry 1, ꢁ=ꢀ ¼ 78=22). These results indicate that the pre-
sent mannosylations were influenced by the kinds of activa-
tor acids. Though the reasons why these acids induced the
stereoselectivities are not yet clear, significant effects of
the acids were certainly shown.
Next, reaction conditions were examined by taking up the
reaction of 2 with 1 using 20 mol% catalyst, HB(C6F5)4
(Table 2). High ꢀ-stereoselectivity was observed when the
mannosylation was carried out in CH2Cl2, a nonpolar solvent,
at À78 ꢀC (Entry 3). On the other hand, the same mannosylation
afforded disaccharide with ꢁ-stereoselectivity in a nitrile sol-
vent (Entry 1). The nitrile solvent was known to be effective
Copyright ꢀ 2003 The Chemical Society of Japan

Chemistry Letters Vol.32, No.5 (2003)
443
Table 2. Effects of solvent and reaction temperature
Finally, in order to extend the scope of the present reaction,
ꢀ-stereoselective mannosylation of several glycosyl acceptors
such as thioglycoside 4, glycosyl fluoride 5, 4-hydroxyl methyl
glycoside 6 and glucosamine derivative 7 with 1 were tried at
À78 ꢀC (Table 3). All glycosyl acceptors having primary hy-
droxyl group reacted smoothly at À78 ꢀC to afford the desired
disaccharides in high yields with high ꢀ-stereoselectivities (En-
tries 1, 2).13 Furthermore, a good ꢀ-stereoselectivity was ob-
served in the similar mannosylation using 6 or 7 (Entries 3,
4). To the best of our knowledge, this is the highest yield of
ꢀ-11 disaccharide by direct mannosylation between 2,3,4,6-tet-
ra-O-benzyl-mannosyl donor and 7. It was also noted that the
chemoselective mannosylations using glycosyl acceptors such
as ethyl 3-O-acetyl-O-4- benzyl-2-deoxy-2-phthalimido-1-thio-
ꢀ-D-glucopyranoside (4) or 2,3,4-tri-O- benzyl-ꢀ-D-glucopyra-
nosyl fluoride (5) gave good results as well without giving any
damage to thio- or fluoro-linkage, respectively (Entries 1, 2).
The donor 1 has a potent and characteristic feature in con-
structing the ꢀ-mannoside and enabled the mannosylation to
achieve higher ꢀ-stereoselectivity at À78 ꢀC in CH2Cl2. Also,
it was found that the counter anion of acid catalysts influenced
the ꢀ-stereoselectivity, and that the highest ꢀ-stereoselectivity
was observed when HB(C6F5)4 was used. Further studies on
the effect of hydroxyl protecting group of mannosyl ben-
zothiazoate on stereoselectivity and on mechanism for ꢀ-stereo-
selectivity are now in progress.
BnO
BnO
Donor 1 (1.2 equiv.)
O
BnO
HB(C6F5)4 (20 mol%)
MS 5A (3 g/mmol)
+
BnO
HO
O
O
O
BnO
BnO
BnO
BnO
0.5 h
BnO
2 (1.0 equiv.)
OMe
BnO
OMe
3
a
Entry
Temp. /°C
Yield /% (α/β)
Solvent
49b (73/27)
89 (38/62)
96 (16/84)
1
2
3
EtCN
Et2O
−78
−78
−78
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
92 (28/72)
98 (22/78)
−94
−60
−30
0
4
5
6
7
quant. (45/55)
quant. (59/41)
aThe
α /β ratios were determined by isolations of both stereoisomers.
bThe reaction was carried out for 1 h.
for the construction of ꢁ-mannoside.3;5;12 It was further ob-
served that the present mannosylation using 1 proceeded even
at À94 ꢀC (Entry 4) and ꢀ-stereoselectivities were shown at
the temperatures ranging from À60 ꢀC to À94 ꢀC (Entries 3,
4, 5). However, ꢀ-stereoselectivties were not observed when
the temperatures were À30 ꢀC to 0 ꢀC (Entries 6, 7), and this
was probably because SN1-type process took place competi-
tively and thus ꢁ-mannoside was given at those higher tempera-
tures.
This study was supported in part by the Grant of the 21st
Century COE Program from the Ministry of Education, Culture,
Sports, Science and Technology (MEXT), Japan.
Table 3. Mannosylation of several acceptors
Donor 1 (1.2 equiv.)
BnO
HB(C6F5)4 (20 mol%)
BnO
BnO
BnO
References and Notes
1
O
+
Reviews: K. Toshima and K. Tatsuta, Chem. Rev., 93, 1503 (1993);
V. Pozsgay in ‘‘Carbohydrate in Chemistry and Biology, Part 1,’’ ed.
MS 5A (3 g/mmol)
CH2Cl2, −78 °C, 0.5 h
Acceptor (1.0 equiv.)
ROH
OR
disaccharide
by B. Ernst, G. W. Hart, and P. Sinay, WILEY-VCH, Weinheim etc.
¨
a
(2000), p 319; J. J. Gridley and H. M. I. Osborn, J. Chem. Soc., Per-
kin Trans. 1, 2000, 1471.
T. Yamanoi, K. Nakamura, H. Takeyama, K. Yanagihara, and T.
Inazu, Bull. Chem. Soc. Jpn., 67, 1359 (1994).
O. J. Plante, R. B. Andrade, and P. H. Seeberger, Org. Lett., 1, 211
(1999); O. J. Plante, E. R. Palmacci, and P. H. Seeberger, Org. Lett.,
2, 3841 (2000).
H. Paulsen and O. Lockhoff, Chem. Ber., 114, 3102 (1981); P.
Garegg and P. Ossowski, Acta Chem. Scand., B37, 249 (1983); C.
A. A. van Boeckel and T. Beetz, Recl. Trav. Chim. Pays-Bas, 106,
596 (1987).
Entry
Acceptor (ROH)
Yield /% (α/β)
Product
HO
2
3
O
BnO
83 (10/90)
1
8
SEt
AcO
PhthN
4
HO
O
BnO
4
5
F
BnO
BnO
5
82 (11/89)
77 (25/75)
89 (30/70)
2
3
9
BnO
K. Toshima, K. Katsumi, and S. Matsumura, Synlett, 1998, 643; H.
Nagai, K. Kawahara, S. Matsumura, and K. Toshima, Tetrahedron
Lett., 42, 4159 (2001).
O
HO
BnO
10
BnO
OMe
6
´
6
7
G. Hodosi and P. Kovac, J. Am. Chem. Soc., 119, 2335 (1997).
O
3
V. K. Srivastava and C. Schuerch, Carbohydr. Res., 79, C13 (1980);
A.-H. Adel, Abdel-Rahman, J. Simon, E. S. El Ashry, and R. R.
Schmidt, Angew. Chem., Int. Ed. Engl., 41, 2972 (2002).
D. Crich and S. Sun, J. Org. Chem., 61, 4506 (1996); D. Crich and
M. Smith, J. Am. Chem. Soc., 124, 8867 (2002).
K. Tatsuta and S. Yasuda, Tetrahedron Lett., 37, 2453 (1996);
W.-S. Kim, H. Sasai, and M. Shibasaki, Tetrahedron Lett., 37,
7797 (1996).
OBn
O
4
11
OH
N
8
9
7
aThe
α/β ratios were determined by isolations of both stereoisomers.
BnO
BnO
BnO
BnO
BnO
BnO
BnO
O
O
O
O
BnO
10 T. Mukaiyama, T. Hashihayata, and H. Mandai, Chem. Lett., in press.
11 HB(C6F5)4 and some protic acids were generated according to literal
procedures. H. Jona, H. Mandai, W. Chavasiri, K. Takeuchi, and T.
Mukaiyama, Bull. Chem. Soc. Jpn., 75, 291 (2002).
12 G. Wulff and G. Rohle, Angew. Chem., 86, 173 (1974).
13 All stereochemistries of novel mannosides were confirmed by gem-
inal 13C-1H coupling constants of anomeric positions. K. Bock and
C. Pedersen, J. Chem. Soc., Perkin Trans. 2, 1974, 293.
O
O
BnO
AcO
BnO
SEt
F
BnO
8
9
NPhth
BnO
O
OBn
BnO
O
BnO
BnO
BnO
BnO
BnO
BnO
BnO
BnO
O
O
O
BnO
O
O
N
3
BnO
OMe
10
11
Published on the web (Advance View) April 16, 2003; DOI 10.1246/cl.2003.442