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Stereoselective synthesis of a core glycoheptaose of bisected biantenarry complex type glycan of glycoproteins
Tetrahedron Letters,Vol.30,No.33,pp Printed in Great Britain
0040-4039/89 $3.00 Perqamon Press plc
4417-4420,1989
STEREOSELECTlVESYNTHESISOFACOREGLYCOHEPTAOSEOFBISECTEDBIANTENARRYCOMPLEX
+ .OO
TYPE
GLYCAN OF GLYCOPROTElNSl
FumitoYamaLaki, Tomoo Nukada, Yukishige Ito, Susumu Sate, and Tomoya Ogawa* RIKEN (The Institute of Physical and Chemical Research), Wako-shi, Saitama, 351-01 Japan Abstract:
A stereocontrolled
glycoprotcin
was
Complex
type
1 and
“bisected”
found
in the glycan
malignant
N-linked
of glycoproteins
glycans2
type such as 2.
complex
of glycoproteins The biological
tissues.
as well
synthesis of a core glycoheptaose of “bisected” by use of stereoselective glycosylation.
achieved
as biosynlhetic
may be classified
The “bisecting”
isolated
from
role of bisecting
GlcNAc
complex
type
into two groups,
residue
glycans
complex
type such as
at 4-O of ManP residue
tissues3
such
GlcNAc
has been discussed
as hcmatopoietic
cells,
kidney,
in terms
of a
has been oviduct
of glycan
and
conformaiton4
regulatiox?. R’\
NeuAca-
4GlcNAcf3
6GalP -
-
ZManu FP
NeuAca-
4GlcNAc$
6GalP -
NeuAcu-
6GalP-
NeuAca-
GGalP-
4GlcNAcP
6,
1986,
In
we reported
As part
here
a synthetic
close
connection
glycooligoses The
were
target
donors
6*,12,
acceptor
to a core
recently
molecule
and a disaccharide
3 Cl3CCN-DBU acceptor
DEAD
l5 in CH2Cl2
yield (I (Bur’3Sn)2016,
DBU in (CH2Cl)2). according acceptor
(CH2C1)2
according
The formation effect20
(Scheme
and
between subsequent
“bisected”
approaches
to the glycan
of glycoproteins, complex
we describe
type
glycans.
to the synthesis
In
of “biscctcd”
stepwise
as shown
2).
into
four
in Scheme
efficient
monosaccharide
1 based
preparative
Readily
available
routes
diol 1311
Two glycosyl
synthons
Conversion
deacetylaiton
of 13
Since
into
with
for the preparation
of BF3sEt20-MS-AW300
of
MeOPhOH-PhgPin 4 steps in 50%
3 PdC12-AcONa-aq.AcOH,
afforded
glgcosyl
10 and a glycosyl
of 13 into 1.5l 2 was achieved
by NaOMe-MeOH
6. 8. 10, 12
2 PdCl2-AcONa-
14 and 15 required
Treatment
2 Ac20-pyridine,
14 and 15 in the presence
donor
was converted in DMF.
donors analysis.
to a glcosyl
yield (1 Ag20-KI-BnBr
from diol 13 as follows.
glycosyl
on retrosynthetic
4 CCl3CN-
in (CH2Cl)2
the chitobiosyl
at -23”
glycosyl
yield.
with properly
to Paulsen19
of the P-glycoside
of 4-0-acetyl
3 that correspond
type glycans
in various
that different
then BnBr-Bun4NBr17,
Coupling
of 11
4GlcNAc 1
of undecasaccharide of complex
4 present
an 84% yield of 14 12.’
11 l 2 in 73% ovcrall
Glycosyiation
11
in (CH2Cl)214).
afforded
to Schmidt18
-
2 3
studies
glycoheptaose
11 were obtainable
overall
R* = GlcNAcP
4GlcNAQ
3
synthesis6
been repoted,
examined
the glycosyl
= Fuca,
4
disconnected
have
aq.AcOH13,
= R2 H
R’
bMan!3-
10 1 2 m 3 steps in 55% overall
trichloroacetimidate
R’
2
,‘J
it is to bc noted
acceptor
S9 and 12lO
i_
reportcd7*10.
4 was
glycosyl
11 were first
4’
on synthetic
our results,
4GlcNAcP/
\
-2Mana
a stereocontrolled
approach with
-2Mana
5
of our project
:Manp--
ZMenu
5’ 4GlcNAcb
6
part of 1.
-
;GICNAC~--ASIJ
.6 7
protected
mannosyl
gave P-glycoside
1612
16 as a major product
in the donor
12,
since
an
donor
12 in the presence
and a-isomer
in a ratio of 2S:l
analogous 4417
glycosyl
of Ag silicate-MS4A
in 48 and
1812
19% yield.
may be explained
donor,
in
respectively.
as a substituent
3,6-di-O-allyl-2,4-di-o-benzyl-a-
4418
D-mannopyranosyl
Design
Synthesis
reaction
F 4’
Fuca
Mana 9
’ ‘cs
~
acceptor
,GlcNAcP
GlcNAcP-
iMa+
Mana’
4GlcNAcD
3
’
bromide a similar
gave21
ratio of 1:l.
1
2
4
with
p- and a-glycoside
Deacetylation
LiOH-H202
in THF gave a 98% yield of
171 2 which
upon
glycosylation
(BF3*Et20-MS-AW300) I Mana
+ -
H\
hmKa”r
A
4GlcNAcP
with the imidate
10 gave a 94% yield of 1912.
~GICNAC
: Manp-
Conversion
of 19
into
tetrasaccharide
S”0
=
I
glycosyl
acceptor
corresponds
2212,
that
to 7 in Scheme
1, was done
in 3 steps via 20 l2 and 21 l2 overall
CH2Cl2 BnOH 4ManP
+4GlcNAcp
-
L ‘2
glycosylation
(All
I allyl,
MP E MeOPh)
suitably
protected
in order
chain
further
of such
gave
mono-
2312
and 2412
and
2512
dcprotcclion
corresponding
prcscnce
to 5 in Scheme
of 26 via 2712
Ac20-pyridine-DMAP, rhose25
complex
type
glycan
glycans
a versatile
Highly
stereosclective
into 4’ 2 was achieved
3 NaOMc-MeOH,
of related
In conclusion,
1.
by (NH4)2Ce(N03)6
m (CH2C1)2-DMF
of C~BQ-B~“~NB~~~
Dcprotcction
with
of 24 was achieved23
isolated and
from
has
natural
been
the desired
in MeOH).
glycans
as 2,
product
with
23 was
8 to give a 36%
of 24.
of 25
to give a 74% yield of
with
thioglycosidc 2612
6 in the
in 77% yield.
yield (1 NH2NH2sH20-EtOH
80”, 2
lH N.m.r. data of 4 was in good agreement
sources.
synthetic established
route
to a core
by employing
22.
PhlhN Scheme
at O-2 for the
extended
in 34 and 37% yield,
again
glycohcptaoside
in 4 steps in 90% overall
4 10% Pd/C-H2
stereocontrolled
2 of glycoproteins
afforded
to elongate
diglycosylated
in 8:l CH3CN-H20
glycosylation
89 which is
Pentasaccharide
glycosylated yield
Sclcct~ve
of 22 with large donor
respectively. 1
Silver triflate
of mannosyl
synthesis
Scheme
in
at -55”. 3 BF3*Et20-MS-AW300-
excess
glycan
I
2 C13CCN-DBU
in (CH2Cl)2).
promoted
4GlcNAc
in 64%
yield (1 (Ph3P)3RhCl-DABCO,
then HgC12-Hg022.
H-
in a
of 16 by
Q
A
GlcNAcb
upon
glycosyl
2 ‘3
glycoheptaose a key
4 of “bisected”
gfycotetraosyl
intermediate
10
-/
12
R = AC
17
R=H
‘L-9
-
19
Scheme
3
22
R’,
2L
R’,R’=H,Ac
We thank Dr. J. Uzawa and Mrs. T. Chijimatsu
and Ms. M. Yoshida
and her staff for the &mental
Moriwaki
for
technical
Refcrcnce
and Notes
1) 2)
3)
4)
5)
their
R=MP R-H
R2 = Phth
Acknowledgment.
analyses.
22 3
ior recording
and measuring
We also thank Ms. A. Takahashi
the NMR spectra and Ms. K.
assistance
Part 63 in the series “Synthetic Studies on Cell-Surafce Glycans”. For Pat 62, M. Mori, Y Ito , and T. Ogawa, Carbohydr. Res. in press. R. Kornfeld and S. Kornfcld. Ann. Rev. Biochem., 45 217 (1976); J. Montrcuil. Pure and Appl. Chem.. 42 43 (1975); Adv. Carbohydr. Chem. Biochem., 37 158 (1980); E. G. Berger, E. Buddecke, J. P. Kamerling. A. Kobata, J. C. Paulson, and J. F. G. Vliegcnthart, Experienfia, 38 1129 (1982). G. Strecker, M.-C. Herlant-Peers, B. Fournet, and J. Montreuil. Eur. J. Biochem., 81 165 (1977); T. Ohkura, T. Isobc, K. Yamashita, and A. Kobata, Biochemiswy, 24 503 (1984); A. Pierce-Crete], H. Debray, J. Montreuil, G. Spik, H. van Halhcck, J. H. G. M. Mutsaers, and J. F. G. Vliegenthart, Eur. J. Biochem., 139 337 (1984); A. G. C. Renwick, T. Mizuochi, and A. Kobata, J. Bioch~m., (Tokyo). 101 1209 (1987). K. Bock, J. Amarp, J. LBm~gren, Eur. J. Biochem., 129 171 (1982); J.-R. Brisson and J. P. Carver, Oiochemislry, 22 3671 (1983): G. Savvidou, M. Klein, A. A. Grcy, K. J. Dorrington, and J. P. Carver, ibid., 23 3736 (1984); H. Paulsen, T. Pctcrs, V. Sinnwclf, R. Lebuhn, and B. Meyer, Liebigs Ann. C/rem.. 951 (1954). 489 (1985); S. W. Homans, R. A. Dwck, J. Boyd, M. Mahmoudian, W. G. Richard, and T. W. Radcmachcr. i3rochemislry. 25 6342 (1986). H. Schachtcr. S. Narasimhan, P. Glceson, and G. Vella, Can. J. Biochem., 61 1049 (1983); J.-R. Brisson and J. P. Carver, Can. J. Biochem., 61 1067 (1983); S. Narasimhan, H. Schachter, and S. Rajalakshmi, J. &of. Chem., 263 1273 (1988).
0040-4039/89 $3.00 Perqamon Press plc
4417-4420,1989
STEREOSELECTlVESYNTHESISOFACOREGLYCOHEPTAOSEOFBISECTEDBIANTENARRYCOMPLEX
+ .OO
TYPE
GLYCAN OF GLYCOPROTElNSl
FumitoYamaLaki, Tomoo Nukada, Yukishige Ito, Susumu Sate, and Tomoya Ogawa* RIKEN (The Institute of Physical and Chemical Research), Wako-shi, Saitama, 351-01 Japan Abstract:
A stereocontrolled
glycoprotcin
was
Complex
type
1 and
“bisected”
found
in the glycan
malignant
N-linked
of glycoproteins
glycans2
type such as 2.
complex
of glycoproteins The biological
tissues.
as well
synthesis of a core glycoheptaose of “bisected” by use of stereoselective glycosylation.
achieved
as biosynlhetic
may be classified
The “bisecting”
isolated
from
role of bisecting
GlcNAc
complex
type
into two groups,
residue
glycans
complex
type such as
at 4-O of ManP residue
tissues3
such
GlcNAc
has been discussed
as hcmatopoietic
cells,
kidney,
in terms
of a
has been oviduct
of glycan
and
conformaiton4
regulatiox?. R’\
NeuAca-
4GlcNAcf3
6GalP -
-
ZManu FP
NeuAca-
4GlcNAc$
6GalP -
NeuAcu-
6GalP-
NeuAca-
GGalP-
4GlcNAcP
6,
1986,
In
we reported
As part
here
a synthetic
close
connection
glycooligoses The
were
target
donors
6*,12,
acceptor
to a core
recently
molecule
and a disaccharide
3 Cl3CCN-DBU acceptor
DEAD
l5 in CH2Cl2
yield (I (Bur’3Sn)2016,
DBU in (CH2Cl)2). according acceptor
(CH2C1)2
according
The formation effect20
(Scheme
and
between subsequent
“bisected”
approaches
to the glycan
of glycoproteins, complex
we describe
type
glycans.
to the synthesis
In
of “biscctcd”
stepwise
as shown
2).
into
four
in Scheme
efficient
monosaccharide
1 based
preparative
Readily
available
routes
diol 1311
Two glycosyl
synthons
Conversion
deacetylaiton
of 13
Since
into
with
for the preparation
of BF3sEt20-MS-AW300
of
MeOPhOH-PhgPin 4 steps in 50%
3 PdC12-AcONa-aq.AcOH,
afforded
glgcosyl
10 and a glycosyl
of 13 into 1.5l 2 was achieved
by NaOMe-MeOH
6. 8. 10, 12
2 PdCl2-AcONa-
14 and 15 required
Treatment
2 Ac20-pyridine,
14 and 15 in the presence
donor
was converted in DMF.
donors analysis.
to a glcosyl
yield (1 Ag20-KI-BnBr
from diol 13 as follows.
glycosyl
on retrosynthetic
4 CCl3CN-
in (CH2Cl)2
the chitobiosyl
at -23”
glycosyl
yield.
with properly
to Paulsen19
of the P-glycoside
of 4-0-acetyl
3 that correspond
type glycans
in various
that different
then BnBr-Bun4NBr17,
Coupling
of 11
4GlcNAc 1
of undecasaccharide of complex
4 present
an 84% yield of 14 12.’
11 l 2 in 73% ovcrall
Glycosyiation
11
in (CH2Cl)214).
afforded
to Schmidt18
-
2 3
studies
glycoheptaose
11 were obtainable
overall
R* = GlcNAcP
4GlcNAQ
3
synthesis6
been repoted,
examined
the glycosyl
= Fuca,
4
disconnected
have
aq.AcOH13,
= R2 H
R’
bMan!3-
10 1 2 m 3 steps in 55% overall
trichloroacetimidate
R’
2
,‘J
it is to bc noted
acceptor
S9 and 12lO
i_
reportcd7*10.
4 was
glycosyl
11 were first
4’
on synthetic
our results,
4GlcNAcP/
\
-2Mana
a stereocontrolled
approach with
-2Mana
5
of our project
:Manp--
ZMenu
5’ 4GlcNAcb
6
part of 1.
-
;GICNAC~--ASIJ
.6 7
protected
mannosyl
gave P-glycoside
1612
16 as a major product
in the donor
12,
since
an
donor
12 in the presence
and a-isomer
in a ratio of 2S:l
analogous 4417
glycosyl
of Ag silicate-MS4A
in 48 and
1812
19% yield.
may be explained
donor,
in
respectively.
as a substituent
3,6-di-O-allyl-2,4-di-o-benzyl-a-
4418
D-mannopyranosyl
Design
Synthesis
reaction
F 4’
Fuca
Mana 9
’ ‘cs
~
acceptor
,GlcNAcP
GlcNAcP-
iMa+
Mana’
4GlcNAcD
3
’
bromide a similar
gave21
ratio of 1:l.
1
2
4
with
p- and a-glycoside
Deacetylation
LiOH-H202
in THF gave a 98% yield of
171 2 which
upon
glycosylation
(BF3*Et20-MS-AW300) I Mana
+ -
H\
hmKa”r
A
4GlcNAcP
with the imidate
10 gave a 94% yield of 1912.
~GICNAC
: Manp-
Conversion
of 19
into
tetrasaccharide
S”0
=
I
glycosyl
acceptor
corresponds
2212,
that
to 7 in Scheme
1, was done
in 3 steps via 20 l2 and 21 l2 overall
CH2Cl2 BnOH 4ManP
+4GlcNAcp
-
L ‘2
glycosylation
(All
I allyl,
MP E MeOPh)
suitably
protected
in order
chain
further
of such
gave
mono-
2312
and 2412
and
2512
dcprotcclion
corresponding
prcscnce
to 5 in Scheme
of 26 via 2712
Ac20-pyridine-DMAP, rhose25
complex
type
glycan
glycans
a versatile
Highly
stereosclective
into 4’ 2 was achieved
3 NaOMc-MeOH,
of related
In conclusion,
1.
by (NH4)2Ce(N03)6
m (CH2C1)2-DMF
of C~BQ-B~“~NB~~~
Dcprotcction
with
of 24 was achieved23
isolated and
from
has
natural
been
the desired
in MeOH).
glycans
as 2,
product
with
23 was
8 to give a 36%
of 24.
of 25
to give a 74% yield of
with
thioglycosidc 2612
6 in the
in 77% yield.
yield (1 NH2NH2sH20-EtOH
80”, 2
lH N.m.r. data of 4 was in good agreement
sources.
synthetic established
route
to a core
by employing
22.
PhlhN Scheme
at O-2 for the
extended
in 34 and 37% yield,
again
glycohcptaoside
in 4 steps in 90% overall
4 10% Pd/C-H2
stereocontrolled
2 of glycoproteins
afforded
to elongate
diglycosylated
in 8:l CH3CN-H20
glycosylation
89 which is
Pentasaccharide
glycosylated yield
Sclcct~ve
of 22 with large donor
respectively. 1
Silver triflate
of mannosyl
synthesis
Scheme
in
at -55”. 3 BF3*Et20-MS-AW300-
excess
glycan
I
2 C13CCN-DBU
in (CH2Cl)2).
promoted
4GlcNAc
in 64%
yield (1 (Ph3P)3RhCl-DABCO,
then HgC12-Hg022.
H-
in a
of 16 by
Q
A
GlcNAcb
upon
glycosyl
2 ‘3
glycoheptaose a key
4 of “bisected”
gfycotetraosyl
intermediate
10
-/
12
R = AC
17
R=H
‘L-9
-
19
Scheme
3
22
R’,
2L
R’,R’=H,Ac
We thank Dr. J. Uzawa and Mrs. T. Chijimatsu
and Ms. M. Yoshida
and her staff for the &mental
Moriwaki
for
technical
Refcrcnce
and Notes
1) 2)
3)
4)
5)
their
R=MP R-H
R2 = Phth
Acknowledgment.
analyses.
22 3
ior recording
and measuring
We also thank Ms. A. Takahashi
the NMR spectra and Ms. K.
assistance
Part 63 in the series “Synthetic Studies on Cell-Surafce Glycans”. For Pat 62, M. Mori, Y Ito , and T. Ogawa, Carbohydr. Res. in press. R. Kornfeld and S. Kornfcld. Ann. Rev. Biochem., 45 217 (1976); J. Montrcuil. Pure and Appl. Chem.. 42 43 (1975); Adv. Carbohydr. Chem. Biochem., 37 158 (1980); E. G. Berger, E. Buddecke, J. P. Kamerling. A. Kobata, J. C. Paulson, and J. F. G. Vliegcnthart, Experienfia, 38 1129 (1982). G. Strecker, M.-C. Herlant-Peers, B. Fournet, and J. Montreuil. Eur. J. Biochem., 81 165 (1977); T. Ohkura, T. Isobc, K. Yamashita, and A. Kobata, Biochemiswy, 24 503 (1984); A. Pierce-Crete], H. Debray, J. Montreuil, G. Spik, H. van Halhcck, J. H. G. M. Mutsaers, and J. F. G. Vliegenthart, Eur. J. Biochem., 139 337 (1984); A. G. C. Renwick, T. Mizuochi, and A. Kobata, J. Bioch~m., (Tokyo). 101 1209 (1987). K. Bock, J. Amarp, J. LBm~gren, Eur. J. Biochem., 129 171 (1982); J.-R. Brisson and J. P. Carver, Oiochemislry, 22 3671 (1983): G. Savvidou, M. Klein, A. A. Grcy, K. J. Dorrington, and J. P. Carver, ibid., 23 3736 (1984); H. Paulsen, T. Pctcrs, V. Sinnwclf, R. Lebuhn, and B. Meyer, Liebigs Ann. C/rem.. 951 (1954). 489 (1985); S. W. Homans, R. A. Dwck, J. Boyd, M. Mahmoudian, W. G. Richard, and T. W. Radcmachcr. i3rochemislry. 25 6342 (1986). H. Schachtcr. S. Narasimhan, P. Glceson, and G. Vella, Can. J. Biochem., 61 1049 (1983); J.-R. Brisson and J. P. Carver, Can. J. Biochem., 61 1067 (1983); S. Narasimhan, H. Schachter, and S. Rajalakshmi, J. &of. Chem., 263 1273 (1988).