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Synthesis of a linear, hexahexosyl unit of a high-mannose type of glycan chain of a glycoprotein
Carbohydrare Resrorch, 123 (1983) Cl%C15 Elsevier Science Publishers R.V.. Amsterdam
Preliminary
- Printed
in The
Netherlands
communication
Synthesis of a linear, hexahexosyl of a glycoprotein*
unit of a high-mannose
type of glycan chain
TOMOYA OGAWA**, TOM00 NUKADA, and TOORU KITAJIMA The hmimte (Received
of Physrcnl August
In
1978,
8th,
and Chemical
1983;
accepted
L.letai.*,
and,
Research,
Wake-shi.
for publication,
in
1979,
Liu
Soitnmu. 3’51 /Japan)
August
er al.’
18th.
1983)
p~upusrd
type glycan I.111 1980. Ugalde etaL4 assigned glr1copyranoayl part of 1 3s ~C,lc(1~3)aGlc(l~3)uC:lc(l-3) mannose
the
ihe
~11uctu1e
ut
the
high-
stereuchemiatry
UT the tri-
f coni
experimfnts
inliibltlon
with glueosidases. In order to provide synthetic support Cur the proposed structure I( we havestudied an approach to 3 total synthesis of I with reg~oand~ierewd~em~cnl con~roi. According to retrosynthetic considerations. structure 1 WIS divided into three parts, nanlely, 2. 3, and 4. Because synthetic routes to the structural equivalents of 2 (ICI. 5) and 3 (ref. 6) had already been established, we describe here a synthesis of the linear hexasaccharide 4. Retrosynthetic considerations mdlcatcd that the target structure 4 m&t be reconstructed from the disaccharide synthons 6, 7. and 8. As the ayntheiic equivalerrts 9 (ref. 7) and 10 (ref. 81, corresponding to 6 and 75 are already available. we first describe the synthesis of IX, which corresponds to the synthon 8.
Glycosidation of 16 (ref. 10) with 15 in the presence of AgOSO,CF,-powdered molecular sicvev 4A in CI(CHZ)ZC1 at -5” afforded a 73% yield of a I~~Y~LITCof 17 and 19 in the ratio of3:l :for 17. Sc(CDC1,): 98.7 (C-I b, ‘.& 170.9 HZ). 96.4 (C-l a, lJCH 168.5 Hz);for l!?.Sc (CDCI,): 100.5 (C-lh, ‘JCH 153.X Hz). 97.0 (C-l ia. ‘,JC~ I h:.’ Hz). In the presence of Hg(CNJz IIgBrz, howcvcr,glycosidatlm of 16 (lef. IO) with 1.5 m Cl(CHz)zCl
gave a 79% yield of the ct anomer
17. lo;],, +62.8’.
Dracetylat~on
*Synthetic Studies on Cell-surface Glycana, Part XXVI. T’or Part XXV, see ref. 1. **To whom enqulrics should be addressed. ***valucl of [a] u were measured for CIICI, solutions at 25”. unless noted otherwise. La1D recorded gaw satisfactory data for elemental analyses.
0008~6215/83/$03
00
Q 1983
Elsevier
Science Publishers
B.V
of 17 nf.
Compounds wllh
PRELIMINARY
COMMUNICATION
M-24
‘6
M-2M’
Cl3
3M
3
G-
A
2G-3G--3Pl--X
HZM-ZM-OBn
G-,_OBn 7
8
10
9
Bn = PhCH2
forded 18, [aID +56.8”, RF 0.73 in 3: 1 toluene-THF, which was glycosylated with the kojibiosyl donor’ 10, [a],, +219.5”, m.p. 136~-138’ (EtlO), in the presence of AgOSOzCF3-powdered tected tetrasaccharide (C-lb,
molecular sieves 4A in Cl(CH,)&!l, 20, [aID +104.4’,
‘JCH 167.2 Hz), 96.2 (C-la,
to give a 59% yield of the pro-
RF 0.50 in 3: 1 toluene-THF;
‘JCH 169.7 Hz), 95.1 (C-Id,
‘JCa
6~ (CDC13): 98.6 174.6 Hz), and 94.8
Cl4
I’RCLI’LIINARY
COIlblLlNICATION
PRELIMINARY
COMMUNICATION
Cl5
(C-lc. ‘J,, 175.8 Hz). Debenzylation of 20 by catalytic, hydrogen transfer” with 10% P&C, HCO,H, and MeOH for 1 h at Xl0 gave 21, and acetylation of 21 afforded a 79% yield uf tlrc: peracetylated tetrasaccharide 22, [aID +I 11 S”. Deacetylatlon of 21 with NaOMc-MeOH gave the free tetrasaccharidc 23: [IX],, +37.5O (H,O), RF 0.88 in 1:8:1 AcOH--MeOHpH,O;SH (400 Hz, D,O): 5.169 (H-laa, J 1.71Hz), 4.928 (H-lap, singlet), 5.199 (II-ld, J 3.7 Hz), 5.270 (H-lt$,J4.4 Hz), 5.281 (H-lba, J 4.6 Hz), and 5.547 (H-lc, J 3.4 Hz). Treatment of 22 with HBI AcOH in Cl12C12 gave tetrasaccharide donor 24, RF 0.40 in 3:2 toluenc-THF. 6, 6.31 (H-la, singlet), which corresponds to the synthon 5. The reaction of 24 with the mannohiosyl acceptor 9 in the presence of AgOS02CF3powdered molecular sieves 4A in CI(CH2)2Cl for S h at 20” afforded a 56% yield of the prg>tpcted hexasaccharide 25, [aID +7S.0°,R, 0.30 in 5: 1 toluene_THF, which was subJetted to debenzylation (10% Pd X, HC02H, MeOIl’) and deacetylation (NaOMe-MeOH), lo give the target, linear hexasaccharide 4: [[Y]~ +104.8’ (H,O). RF 0.46 in 1:s: 1 AcOHMeOH-H,O;SH (400 MHz, D,O): 5.543 (H-le, d,J 3.7 Ilz), 5.385 (H-la, s), 5.311 (H-lb, s), 5.283 (H-ld, d, J3.9 Hz), 5.197(H-lf, d, J3.7 IL), and 5.049 (H-lc, d,J 1.6 Hz). In conclusion, a stereoselective synthesis of the linear hexasaccharide 4 was achieved by using the three disaccharide synthons 9, 10, and 18. ACKNOWLEDGMENTS
We thank Dr. J. Uzawa and Mrs. T. Chijimai.su for recording and measuring the n.m.r. spectra, and Dr. H. Homma and his staff for the elemental analyses. We also thank Mrs. A. Takahashi for her technical assistance. REFERENCES
1 2 3
T. Opawa, T. Kitajima. and T. Nukada, Carbohydr. Res., 123 (1983) CE-Cll. E. Li, I. Tabas, and S. Kornfeld, J. Biol. Chcm., 253 (1978) 7762-7770. T. Liu, B. Stetson, S. J. Turco. S. C. Hubbard, and P. W. Robbins, J. Bhl. Chem.,
254
(1979)
4554-4559. 4 5 6
R. A.
7 8 9
T. Owwa and H. Yamamoto, Carbohydr. Res., 104 (1982) 271-283. W. E. Dick, I. E. Ilodge, and G. E. In&t, Corbohydr. Rev.. 36 (lY74) 319-329. T. Ogawa, S. Nakabayashl, and T. Kitajima, Carhohydr. Res., I14 (1983) 225-236.
10 11
Ugalde, R. J. Staneloni, and L. F. Leloir, Eur. J Btochem., 113 (1980) 97-103. T. Ocwva. T. Kitaiima. and T. Nukada. Cnrbohvdr. REI.. 123 (19X3) CSLC7. T. O&LX+;K. K&o, K. Sasajima, md M. Mat&i, Terrah~dr&,~37 ;1981) 2779-2786.
T. Ogawa and H. Yamamoto, unpublished results. B. El Amin, G. M. Anantharamaiah. G. P. Royer, and G. E. Means, J 34423444; V. S. Rao and A. S. Perlin, Carbohydr T. .I. Nestrick, C?wn. Rev., 74 (1974) 567.-580.
Res.,
83 (1980)
org.
C&m.,
175-177;
44 (1979) G. Brie&r
and
Preliminary
- Printed
in The
Netherlands
communication
Synthesis of a linear, hexahexosyl of a glycoprotein*
unit of a high-mannose
type of glycan chain
TOMOYA OGAWA**, TOM00 NUKADA, and TOORU KITAJIMA The hmimte (Received
of Physrcnl August
In
1978,
8th,
and Chemical
1983;
accepted
L.letai.*,
and,
Research,
Wake-shi.
for publication,
in
1979,
Liu
Soitnmu. 3’51 /Japan)
August
er al.’
18th.
1983)
p~upusrd
type glycan I.111 1980. Ugalde etaL4 assigned glr1copyranoayl part of 1 3s ~C,lc(1~3)aGlc(l~3)uC:lc(l-3) mannose
the
ihe
~11uctu1e
ut
the
high-
stereuchemiatry
UT the tri-
f coni
experimfnts
inliibltlon
with glueosidases. In order to provide synthetic support Cur the proposed structure I( we havestudied an approach to 3 total synthesis of I with reg~oand~ierewd~em~cnl con~roi. According to retrosynthetic considerations. structure 1 WIS divided into three parts, nanlely, 2. 3, and 4. Because synthetic routes to the structural equivalents of 2 (ICI. 5) and 3 (ref. 6) had already been established, we describe here a synthesis of the linear hexasaccharide 4. Retrosynthetic considerations mdlcatcd that the target structure 4 m&t be reconstructed from the disaccharide synthons 6, 7. and 8. As the ayntheiic equivalerrts 9 (ref. 7) and 10 (ref. 81, corresponding to 6 and 75 are already available. we first describe the synthesis of IX, which corresponds to the synthon 8.
Glycosidation of 16 (ref. 10) with 15 in the presence of AgOSO,CF,-powdered molecular sicvev 4A in CI(CHZ)ZC1 at -5” afforded a 73% yield of a I~~Y~LITCof 17 and 19 in the ratio of3:l :for 17. Sc(CDC1,): 98.7 (C-I b, ‘.& 170.9 HZ). 96.4 (C-l a, lJCH 168.5 Hz);for l!?.Sc (CDCI,): 100.5 (C-lh, ‘JCH 153.X Hz). 97.0 (C-l ia. ‘,JC~ I h:.’ Hz). In the presence of Hg(CNJz IIgBrz, howcvcr,glycosidatlm of 16 (lef. IO) with 1.5 m Cl(CHz)zCl
gave a 79% yield of the ct anomer
17. lo;],, +62.8’.
Dracetylat~on
*Synthetic Studies on Cell-surface Glycana, Part XXVI. T’or Part XXV, see ref. 1. **To whom enqulrics should be addressed. ***valucl of [a] u were measured for CIICI, solutions at 25”. unless noted otherwise. La1D recorded gaw satisfactory data for elemental analyses.
0008~6215/83/$03
00
Q 1983
Elsevier
Science Publishers
B.V
of 17 nf.
Compounds wllh
PRELIMINARY
COMMUNICATION
M-24
‘6
M-2M’
Cl3
3M
3
G-
A
2G-3G--3Pl--X
HZM-ZM-OBn
G-,_OBn 7
8
10
9
Bn = PhCH2
forded 18, [aID +56.8”, RF 0.73 in 3: 1 toluene-THF, which was glycosylated with the kojibiosyl donor’ 10, [a],, +219.5”, m.p. 136~-138’ (EtlO), in the presence of AgOSOzCF3-powdered tected tetrasaccharide (C-lb,
molecular sieves 4A in Cl(CH,)&!l, 20, [aID +104.4’,
‘JCH 167.2 Hz), 96.2 (C-la,
to give a 59% yield of the pro-
RF 0.50 in 3: 1 toluene-THF;
‘JCH 169.7 Hz), 95.1 (C-Id,
‘JCa
6~ (CDC13): 98.6 174.6 Hz), and 94.8
Cl4
I’RCLI’LIINARY
COIlblLlNICATION
PRELIMINARY
COMMUNICATION
Cl5
(C-lc. ‘J,, 175.8 Hz). Debenzylation of 20 by catalytic, hydrogen transfer” with 10% P&C, HCO,H, and MeOH for 1 h at Xl0 gave 21, and acetylation of 21 afforded a 79% yield uf tlrc: peracetylated tetrasaccharide 22, [aID +I 11 S”. Deacetylatlon of 21 with NaOMc-MeOH gave the free tetrasaccharidc 23: [IX],, +37.5O (H,O), RF 0.88 in 1:8:1 AcOH--MeOHpH,O;SH (400 Hz, D,O): 5.169 (H-laa, J 1.71Hz), 4.928 (H-lap, singlet), 5.199 (II-ld, J 3.7 Hz), 5.270 (H-lt$,J4.4 Hz), 5.281 (H-lba, J 4.6 Hz), and 5.547 (H-lc, J 3.4 Hz). Treatment of 22 with HBI AcOH in Cl12C12 gave tetrasaccharide donor 24, RF 0.40 in 3:2 toluenc-THF. 6, 6.31 (H-la, singlet), which corresponds to the synthon 5. The reaction of 24 with the mannohiosyl acceptor 9 in the presence of AgOS02CF3powdered molecular sieves 4A in CI(CH2)2Cl for S h at 20” afforded a 56% yield of the prg>tpcted hexasaccharide 25, [aID +7S.0°,R, 0.30 in 5: 1 toluene_THF, which was subJetted to debenzylation (10% Pd X, HC02H, MeOIl’) and deacetylation (NaOMe-MeOH), lo give the target, linear hexasaccharide 4: [[Y]~ +104.8’ (H,O). RF 0.46 in 1:s: 1 AcOHMeOH-H,O;SH (400 MHz, D,O): 5.543 (H-le, d,J 3.7 Ilz), 5.385 (H-la, s), 5.311 (H-lb, s), 5.283 (H-ld, d, J3.9 Hz), 5.197(H-lf, d, J3.7 IL), and 5.049 (H-lc, d,J 1.6 Hz). In conclusion, a stereoselective synthesis of the linear hexasaccharide 4 was achieved by using the three disaccharide synthons 9, 10, and 18. ACKNOWLEDGMENTS
We thank Dr. J. Uzawa and Mrs. T. Chijimai.su for recording and measuring the n.m.r. spectra, and Dr. H. Homma and his staff for the elemental analyses. We also thank Mrs. A. Takahashi for her technical assistance. REFERENCES
1 2 3
T. Opawa, T. Kitajima. and T. Nukada, Carbohydr. Res., 123 (1983) CE-Cll. E. Li, I. Tabas, and S. Kornfeld, J. Biol. Chcm., 253 (1978) 7762-7770. T. Liu, B. Stetson, S. J. Turco. S. C. Hubbard, and P. W. Robbins, J. Bhl. Chem.,
254
(1979)
4554-4559. 4 5 6
R. A.
7 8 9
T. Owwa and H. Yamamoto, Carbohydr. Res., 104 (1982) 271-283. W. E. Dick, I. E. Ilodge, and G. E. In&t, Corbohydr. Rev.. 36 (lY74) 319-329. T. Ogawa, S. Nakabayashl, and T. Kitajima, Carhohydr. Res., I14 (1983) 225-236.
10 11
Ugalde, R. J. Staneloni, and L. F. Leloir, Eur. J Btochem., 113 (1980) 97-103. T. Ocwva. T. Kitaiima. and T. Nukada. Cnrbohvdr. REI.. 123 (19X3) CSLC7. T. O&LX+;K. K&o, K. Sasajima, md M. Mat&i, Terrah~dr&,~37 ;1981) 2779-2786.
T. Ogawa and H. Yamamoto, unpublished results. B. El Amin, G. M. Anantharamaiah. G. P. Royer, and G. E. Means, J 34423444; V. S. Rao and A. S. Perlin, Carbohydr T. .I. Nestrick, C?wn. Rev., 74 (1974) 567.-580.
Res.,
83 (1980)
org.
C&m.,
175-177;
44 (1979) G. Brie&r
and