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A convenient synthesis of both the anomers of ethyl (2,3,4,6-tetra-O-benzyl-D-glucopyranosyl)acetate
Tetrahedron Printed in
Letters,Vo1.28,No.42,pp Great Britain
5047-5048,1987
oo40-4039/87 $3.00 f .OO Pergamon Journals Ltd.
Aa)NVESIIENTSYNIHJZXSOFl30IHlHEANOMERS (2,3,4,6-TEE&+O-FEKZYL-D-GLU
Diego Monti*
, Paola Gramatica, Giovanna Speranza, and Paolo Manitto
Centro di Studio per le Sostanze Organica
e Industriale,
AHSTHACT. by reaction Horner
Naturali
di Milano,
of ethyl
for the synthesis
of tetra-O-benzylglucose
de1 CNH and Dipartimento
via Venezian
di Chimica
21, 20133-Milano,
ITALY
(2,3,4,6-tetra+benzyl-D-glucopyranosyl)acetate,
of alkyl C-glucosides,
can be obtained
with triethyl phosphonoacetate
in good yields
according
to the Wittig-
procedure.
There
is an increasing
merit positions
interest
of carbohydrates.
pyran rings with two oxygenated potential
enzyme
(including
inhibitors
biologically
derivatives
Unfortunately,
alkyl substituents
reactions
at the ano-
polyhydroxylated
tetrahydro-
at the 2- and B-positions
(2) for the synthesis
C-glycosides)
(3). In particular,
to be convenient
the use of 2 and?
reaction
routes
intermediates
for synthetic
for their preparation
(see A and z) are
of complex
natural
products
the C-glucopyranosyl
to prepare
a wide range of alkyl limited
by the
(3a). In fact, they cannot be obtained
purposes
by the
of 2,3,4,6-tetra-Dbenzyl-D-glucopyranose
phenylphosphorane
followed
by Michael
use of the Homer
through
reagent
the nitrile
method
instead of the Wittig
with
(carbethoxymethylene)tri-
to obtain a mixtures
column chromatography)
derivative
has been greatly
i.e. using the Moffat
cyclisation,
(5). We report here an efficient
the single compounds preparing
bond-forming
the resulting
(4).
need of multistep
procedure
in the carbon-carbon
This is because
(1) and chirons
active
J and 3 appear
Cglucosides
Wittig
Organiche
Universita'
Z%eo(- andp- anomers
useful intermediates
OF ElHYL
copyRANosyL)AcFpATE
in good yields.
C-glycosidation
ofJ
and2
(as well as
This method,
based on the
one, was also shown to be successful
in
3.
CH,CO,Et
RoRqoR RO-q;
‘:q:‘““”“qy”” 1
Tvpically, cooled
2
R I CH,Ph
3
triethyl phosphonoacetate
(OOC) suspension
of NaH (100 mmol)
(18.5 ml, 92.4 mnol) was put dropwise under i$ into a in TFIF (40 ml) and the resulting mixture stirred for
5 h at r.t.; 2,3,4,6-tetra-O-benzylglucopyranose reaction
progress
was followed
with HCl and extracted graphed
using
by t.l.c.(6).
with ether.
4
(5 g, 9.2 mnol) was then added and the After ca. 44 h the reaction mixture was acidified
The residue
frcm solvent
the same eluent as for t.l.c.(6),
evaporation,
gave a mixture
when flash chromate
(4.5 g) of comIwund~
and_2
(see
Table I). Each of these could be isolated silica gel column
(hexaneethyl
1 (3a,7) and theo(-anomer Lcovered
acetate
in pure form by repeated flash chromatographies on gave thep-anomer 3~1). In fact, the first semation
2 (8) in 18% and L% yield respectively
from the column Zmost
quantitatively). 5047
(the residual
mixture
being
5048 TABLE l.- Reaction of 2,3,4,6-tetra-&benzylglucopyranosewith triethyl phosphonoacetatein different solvents (a). benzene
n-hexane
74 1.4
12 0.75 47
% Yield of (JtZJ (c) Ratio (L:?) (c) % Yield of 3 (c)
DMSO
DMF
'IXF 92(80)(d) 3.1
TPA (b)
5 1.1 84
40 2.0 58
67 only 2
(a) Reaction conditions as described in the text for TN?; (b) Triethyl phosphonoacetate; (c) determined by t.l.c.(6) using a CAMAG TLC SCANNER (calibrationcurves recorded at 254 nm); (d) isolated yield (in parentheses). Results from experiments performed in different solvents are reported in Table 1. It must be pointed out that the ethyl octenoate 3 (9) is formed as the predominant product in certain solvents, but is absent in benzene, THF, and TPA. Inspection of the data of Table 1 reveals that the best yields of the anomeric mixture (lt2) are obtained in THF, whereas TPA and benzene __ represent the most convenient solvents to prepare the @-and thea-isomer, respectively (the latter after a chromatographic separation). By a procedure analogous to that described above, but using diethyl phosphonoacetonitrileas the alkylating reagent, an anomeric mixture of 1 (11) (=. 2:l in favour of the p-anomer ) was obtained in 55% yield. Acknowledgments: We thank Dr. G. De Dellis for technical assistance. We gratefully acknowledge the Minister0 Rubblica Istruzione of Italy for financial support.
1) M.CXMIELEWSKI, 2) S.HANESSIAN, Oxford.
J.N.BeMIl,LER, and D.P.CmI, Total Synthesis
of Natural
1983; T.D.INCH.,Tetrahedron,
3) See for example:(a) Y.1113, S.MASAMVNE,
M.D.LEWIS,
Carbohydr.Res., 97,Cl (1981). The Chiron Approach, Pergamon
Press,
Products:
40,3161(1984). J.K.CH4,
Y.KISHI, J.Am.Chem.S0~.,104,4976(1982);(b)
K.B.SH4RPLES.S, J.Am.Chem.S0~.,104,6468(1982)
and references
L.A.REED,
cited therein;
(c) B.GIESE, J.DEPUIS, Angew. C&em., Int. Ed. Ezlgl.,22,622(1983). 4) Results to be published. 5) (a) H.CXtRUI, G.H.JONES, J.G.,XXFAT, Soc.,97,4602(19~); F.NICQTR4,
M.L..&WlXX,
(b) B.&'R4SER-REID, R.D.DAWE,
F.RONCXETl'I, G.RUSSO,
L.l?XA,
A.T.CHRISTE7VSm,
and S.K.BYRAM,
J.Am.Chem.
(c)
D. B.TULSHIAN, Can.J. Chem, 5?,1746(1979);
Tetrahedron
Letters,
25,5697
(1984).
6) Silica
(Kieselgel 60 F:;i; Merck) eluent: hexne-ethyl acetate 4~1. 7) Ethyl 3,7-anhydro-2-deoxy-4,5,6,8-tetra-~benzyl-D-glycer~D-~l~octonate: Rf (6) 0.26
'&n.m.r.
(Py-ds,
Z%S),
(J in Hz): 1.08 (3H, t, J=7.5,
and 3.02 (lH, dd, J=3, J'=15) due to -CHzCOIEt; H- 7) ; 3.7-4.2 (2H, q, J=7.5
"C n.m.r H,6.93.
TXS) : 37.70 (C-2); 170.78 C, 74.56; H, 7.04.
(CLXX:,
Found:
H-4);
3.70 (lH, m,
4.10 (lH, ddd, J=3, J'=9, J"=9.5,
4.5-5.1 (BH, m, cH2-Ar); (CO).
;
2,73 (lH, dd, J=9, J'=15)
3.58 (lH, dd, J=J'=9.5,
(4H, 2m, ff-5, H-6, H-8', l&8");
, e?-cH;);
ZH?-%);
7.1-7.7 (2OH, m, aromatic
Anal. Calcd. for C38Hq24:
83);
4.10
protons). C,74.73;
8) Ethyl 3,7-anhydro-2-deoxy-4,5,6,8-tetra-0-benzyl-D-glycer~D-id~octo~te:Rf (6) 0.18; 'Nn.m.r.
(I+-ds,
'I?&),
3.02 (lH, dd, J=8, J'=16) H-8', fi8");
(J in Hz): 1.11 (3H, t, J=7.5, XXfz@); due to -Clf~-m~Et; 3.74 (lH, m, H-7);
4.15 (ZK, q, J=7.5,
z?C&);
2.85 (lH, dd, J=6, J'=l6) and
3.8-4.4 (5H, m, ff4, H-5, H-6, 4.19 (lH, ddd, J=6, S=8, J"=4.8, H-3); 4.5-5.3
(CLXX~, ?Fts) , :32.58 (C-2); (81% m, c?+-Ar); 7.1-7. 7 (2OH, m, aromatic protons). "Gn.m.r. 170.96 (C=O). Anal. Calcd. for c;sE&c2Q: C,74.73; H,6.93. Found: C,74.71; H,7.01. 9) Isolated identical
by column
chromstography
in all respects
-0-bensyl-&glucose
as compound1
with the product
a&,2.
Rf (6); 0.1. It was shown
of the Wittig reaction
and (carbetho~thylene)triphenylphosphorane
been reported
to be stable
10) F.NICWTRA,
F.RQUX?ZTI,
to the intramolecular G.RUSSO,
J.Org.
Michael
between in Q&CN
to be
2,3,4,6tetra-
(10). Cbmpound
addition.
Chem. ,47,5381(1982).
11) K.C.NIOOLALI,R.E.DOLLE, A.CHUCHOL4X&SKI, J.L. RANDALL, J.C.S. Chem.Corms.,( 1984),1253. (Received
in UK 4 August
1987)
3 has
Letters,Vo1.28,No.42,pp Great Britain
5047-5048,1987
oo40-4039/87 $3.00 f .OO Pergamon Journals Ltd.
Aa)NVESIIENTSYNIHJZXSOFl30IHlHEANOMERS (2,3,4,6-TEE&+O-FEKZYL-D-GLU
Diego Monti*
, Paola Gramatica, Giovanna Speranza, and Paolo Manitto
Centro di Studio per le Sostanze Organica
e Industriale,
AHSTHACT. by reaction Horner
Naturali
di Milano,
of ethyl
for the synthesis
of tetra-O-benzylglucose
de1 CNH and Dipartimento
via Venezian
di Chimica
21, 20133-Milano,
ITALY
(2,3,4,6-tetra+benzyl-D-glucopyranosyl)acetate,
of alkyl C-glucosides,
can be obtained
with triethyl phosphonoacetate
in good yields
according
to the Wittig-
procedure.
There
is an increasing
merit positions
interest
of carbohydrates.
pyran rings with two oxygenated potential
enzyme
(including
inhibitors
biologically
derivatives
Unfortunately,
alkyl substituents
reactions
at the ano-
polyhydroxylated
tetrahydro-
at the 2- and B-positions
(2) for the synthesis
C-glycosides)
(3). In particular,
to be convenient
the use of 2 and?
reaction
routes
intermediates
for synthetic
for their preparation
(see A and z) are
of complex
natural
products
the C-glucopyranosyl
to prepare
a wide range of alkyl limited
by the
(3a). In fact, they cannot be obtained
purposes
by the
of 2,3,4,6-tetra-Dbenzyl-D-glucopyranose
phenylphosphorane
followed
by Michael
use of the Homer
through
reagent
the nitrile
method
instead of the Wittig
with
(carbethoxymethylene)tri-
to obtain a mixtures
column chromatography)
derivative
has been greatly
i.e. using the Moffat
cyclisation,
(5). We report here an efficient
the single compounds preparing
bond-forming
the resulting
(4).
need of multistep
procedure
in the carbon-carbon
This is because
(1) and chirons
active
J and 3 appear
Cglucosides
Wittig
Organiche
Universita'
Z%eo(- andp- anomers
useful intermediates
OF ElHYL
copyRANosyL)AcFpATE
in good yields.
C-glycosidation
ofJ
and2
(as well as
This method,
based on the
one, was also shown to be successful
in
3.
CH,CO,Et
RoRqoR RO-q;
‘:q:‘““”“qy”” 1
Tvpically, cooled
2
R I CH,Ph
3
triethyl phosphonoacetate
(OOC) suspension
of NaH (100 mmol)
(18.5 ml, 92.4 mnol) was put dropwise under i$ into a in TFIF (40 ml) and the resulting mixture stirred for
5 h at r.t.; 2,3,4,6-tetra-O-benzylglucopyranose reaction
progress
was followed
with HCl and extracted graphed
using
by t.l.c.(6).
with ether.
4
(5 g, 9.2 mnol) was then added and the After ca. 44 h the reaction mixture was acidified
The residue
frcm solvent
the same eluent as for t.l.c.(6),
evaporation,
gave a mixture
when flash chromate
(4.5 g) of comIwund~
and_2
(see
Table I). Each of these could be isolated silica gel column
(hexaneethyl
1 (3a,7) and theo(-anomer Lcovered
acetate
in pure form by repeated flash chromatographies on gave thep-anomer 3~1). In fact, the first semation
2 (8) in 18% and L% yield respectively
from the column Zmost
quantitatively). 5047
(the residual
mixture
being
5048 TABLE l.- Reaction of 2,3,4,6-tetra-&benzylglucopyranosewith triethyl phosphonoacetatein different solvents (a). benzene
n-hexane
74 1.4
12 0.75 47
% Yield of (JtZJ (c) Ratio (L:?) (c) % Yield of 3 (c)
DMSO
DMF
'IXF 92(80)(d) 3.1
TPA (b)
5 1.1 84
40 2.0 58
67 only 2
(a) Reaction conditions as described in the text for TN?; (b) Triethyl phosphonoacetate; (c) determined by t.l.c.(6) using a CAMAG TLC SCANNER (calibrationcurves recorded at 254 nm); (d) isolated yield (in parentheses). Results from experiments performed in different solvents are reported in Table 1. It must be pointed out that the ethyl octenoate 3 (9) is formed as the predominant product in certain solvents, but is absent in benzene, THF, and TPA. Inspection of the data of Table 1 reveals that the best yields of the anomeric mixture (lt2) are obtained in THF, whereas TPA and benzene __ represent the most convenient solvents to prepare the @-and thea-isomer, respectively (the latter after a chromatographic separation). By a procedure analogous to that described above, but using diethyl phosphonoacetonitrileas the alkylating reagent, an anomeric mixture of 1 (11) (=. 2:l in favour of the p-anomer ) was obtained in 55% yield. Acknowledgments: We thank Dr. G. De Dellis for technical assistance. We gratefully acknowledge the Minister0 Rubblica Istruzione of Italy for financial support.
1) M.CXMIELEWSKI, 2) S.HANESSIAN, Oxford.
J.N.BeMIl,LER, and D.P.CmI, Total Synthesis
of Natural
1983; T.D.INCH.,Tetrahedron,
3) See for example:(a) Y.1113, S.MASAMVNE,
M.D.LEWIS,
Carbohydr.Res., 97,Cl (1981). The Chiron Approach, Pergamon
Press,
Products:
40,3161(1984). J.K.CH4,
Y.KISHI, J.Am.Chem.S0~.,104,4976(1982);(b)
K.B.SH4RPLES.S, J.Am.Chem.S0~.,104,6468(1982)
and references
L.A.REED,
cited therein;
(c) B.GIESE, J.DEPUIS, Angew. C&em., Int. Ed. Ezlgl.,22,622(1983). 4) Results to be published. 5) (a) H.CXtRUI, G.H.JONES, J.G.,XXFAT, Soc.,97,4602(19~); F.NICQTR4,
M.L..&WlXX,
(b) B.&'R4SER-REID, R.D.DAWE,
F.RONCXETl'I, G.RUSSO,
L.l?XA,
A.T.CHRISTE7VSm,
and S.K.BYRAM,
J.Am.Chem.
(c)
D. B.TULSHIAN, Can.J. Chem, 5?,1746(1979);
Tetrahedron
Letters,
25,5697
(1984).
6) Silica
(Kieselgel 60 F:;i; Merck) eluent: hexne-ethyl acetate 4~1. 7) Ethyl 3,7-anhydro-2-deoxy-4,5,6,8-tetra-~benzyl-D-glycer~D-~l~octonate: Rf (6) 0.26
'&n.m.r.
(Py-ds,
Z%S),
(J in Hz): 1.08 (3H, t, J=7.5,
and 3.02 (lH, dd, J=3, J'=15) due to -CHzCOIEt; H- 7) ; 3.7-4.2 (2H, q, J=7.5
"C n.m.r H,6.93.
TXS) : 37.70 (C-2); 170.78 C, 74.56; H, 7.04.
(CLXX:,
Found:
H-4);
3.70 (lH, m,
4.10 (lH, ddd, J=3, J'=9, J"=9.5,
4.5-5.1 (BH, m, cH2-Ar); (CO).
;
2,73 (lH, dd, J=9, J'=15)
3.58 (lH, dd, J=J'=9.5,
(4H, 2m, ff-5, H-6, H-8', l&8");
, e?-cH;);
ZH?-%);
7.1-7.7 (2OH, m, aromatic
Anal. Calcd. for C38Hq24:
83);
4.10
protons). C,74.73;
8) Ethyl 3,7-anhydro-2-deoxy-4,5,6,8-tetra-0-benzyl-D-glycer~D-id~octo~te:Rf (6) 0.18; 'Nn.m.r.
(I+-ds,
'I?&),
3.02 (lH, dd, J=8, J'=16) H-8', fi8");
(J in Hz): 1.11 (3H, t, J=7.5, XXfz@); due to -Clf~-m~Et; 3.74 (lH, m, H-7);
4.15 (ZK, q, J=7.5,
z?C&);
2.85 (lH, dd, J=6, J'=l6) and
3.8-4.4 (5H, m, ff4, H-5, H-6, 4.19 (lH, ddd, J=6, S=8, J"=4.8, H-3); 4.5-5.3
(CLXX~, ?Fts) , :32.58 (C-2); (81% m, c?+-Ar); 7.1-7. 7 (2OH, m, aromatic protons). "Gn.m.r. 170.96 (C=O). Anal. Calcd. for c;sE&c2Q: C,74.73; H,6.93. Found: C,74.71; H,7.01. 9) Isolated identical
by column
chromstography
in all respects
-0-bensyl-&glucose
as compound1
with the product
a&,2.
Rf (6); 0.1. It was shown
of the Wittig reaction
and (carbetho~thylene)triphenylphosphorane
been reported
to be stable
10) F.NICWTRA,
F.RQUX?ZTI,
to the intramolecular G.RUSSO,
J.Org.
Michael
between in Q&CN
to be
2,3,4,6tetra-
(10). Cbmpound
addition.
Chem. ,47,5381(1982).
11) K.C.NIOOLALI,R.E.DOLLE, A.CHUCHOL4X&SKI, J.L. RANDALL, J.C.S. Chem.Corms.,( 1984),1253. (Received
in UK 4 August
1987)
3 has