Highly stereoselective synthesis of α-glycosides of neuraminic acid analogues

Article abstract of DOI:10.1016/S0040-4039(00)60807-9

ε-Hydroxy enol ether 6 was readily prepared from D-gluconolactone via ester formation and selective di-O-isopropylidenation, 2-O-alkylation with triflate 1, selective 5,6-de-O-isopropylidenation and 6-O-silylation, azide introduction, and subsequent E-spe

Full text of DOI:10.1016/S0040-4039(00)60807-9

33, No. 49. pp.
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in
Highly Stereoselective Synthesis of
of Neuraminic Acid
R. Vlahov,
I.
and Richard R. Schmidt*
Konstanz, Postfach 5560,
Chemie,
D-7750 Konstanz, Germany
6 was
with
via
and
1.
and
a-connected
7, which was
into
11, respectively.
N-Acetylneuraminic acid
found in a-connection at the nonreducing end of oligosaccharide chains. The
important function& is exhibited by interactions with the enzymes involved in its metabolism (especially
Scheme 1, A) is a constituent of many glycoconjugates, where it is
of its
lyhransferases and sialidases). For understanding the
complexes a series of analogues has been recently
relationships of such
In this paper we describe the highly
reoselective synthesis of a-glycosidically linked analogues, lacking the
chain
(A, n = 0). which is based on an electrophile initiated cyclisation of
enol ether intermediate B.
in these investigations the
obtained as E/Z-mixtures via a Wittig-Homer procedure, thus causing
of glycoside bond formation.
ted approaches have been applied in the sugar series by
e-hydroxy enol ether precursors
and by
difficulties in the
Scheme
C
B
The efficiency of our strategy is based on the convenient formation of a
of
(intermediate C), its conversion to Ecnol ether B via E-specific g-elimination, and ensuing
and
stereoselective ring closure resulting in the desired a-glycoside A.
The decisive starting material of type B could be
Dgluconolactone (Scheme 2) via
then alkylation of the
regioselective
with simultaneous methyl ester
methyl
group at C-2 with the easily
acid catalyzed selective
butyldiphenyl and
selective
with
group introduction at the C-S atom, affording intermediate 3.
7503

7504
Scheme 2
D-GLUCONOIACTONE
(99%)
1.
2.
THF.
1, r.t. (74%)
1. DOWEX
WX2,
2.
3.
Im., DMF (91%)
(94%)
1. TFA,
DBU,

7505
Treatment of3 with
acid
in
in
formation of
providing
the
which upon acetylation gave derivative 4. Treatment of 4
ene
as base led to abstraction of the proton at C-2’ and
lide derivative 5. Removal of the acetyl
ning, thus the e-hydroxy
group with
resulted
ring ope-
ether 6 in quantitative yield
Compound 6 possesses the desired
for the ensuing highly
and a-steno-
selective cyclization which could be induced by N-iodosuccinimlde
in a quantitative reaction. The of a-glycoside 7 obtained via D as
the data relatlonships between H-3’,
iodide 7 with the presence of catalytic amounts of AIBN (toluene.
8. On the other hand, conversion of N-methyl amide 7 in methyl
as
at low
was derlved
Reduction of
= 9.5
H-S).
30 min)
9 and
and acetylation gave
subsequent
with
when compound 9 was
of
resulted in lactam 10, thus proofing the assignment of the a-configu-
with at for 12 h and then with acetic
11 was isolated in high yield. The compounds were cha-
The results of a shnllar for the highly synthesis of
ration at
hydride the
racterized by their
will be
NOTES
1. This work was support& by the Deutsche Forschungsgemeinsch and the Ponds der Chemischen
dustrie. I.V. is grateful for an Alexander von Humboldt Fellowship.
R. Schauer, Adv.
E. R. Christian,
Len. 31 (1990) 2875. and
Z.
40 (1982) 131; Sialic Acids, Springer-Verlag, Wien, 1982.
2.
3.
Ann. Chem.
and E.
J .
Beau, and R Schauer,
360 (1979) 159; H.J. Gross, R Brossmer,
J. 4
(1987) 145. and
K.
Peale, W. Korytnyk,
Biochem.
(1983) 153;
S.
K.
J.
Res. 167 (1987) 77; J .H. Gross, A.
F.
ibid.
J .C.
Paulson, R
69 (1986)
168 (1987)
M. Hugener, A.
A.
A.
1 88)
R.
and
B.
Z.
R.R. Schmidt,
32 (1991) 7025.
B.
74 (1991) 343, and
T.
Res. 216 (1991) 483; L
P.
and RR Schmidt,
4. K. Suzuki, T.
1982,683; 1525.
29 (1984) 307 1.
Trav.
F.
P.
5.
6.
7.
H. Regeling, E. de Ronville,
Pays-Bus 106 (1987) 461.
(A.
1.5 h): RR
L
and P.
U.
Res. 44 (1975) 1) and
Reichrath, Ber. (1982) 39.
ring,
8. S. Hanessian, P. Lavallee, Can. J. (1975) 2975.
Also deduced from the chemical shift of the vinylic proton (5.12 ppm). see R. Ireland, R Mueller, A.
9.
Willard, J. Am.
E. White, J. Am.
For the synthesis of
259.
77 (1955) 6008.
lactams of
10.
11.
via a
see: Y.F. Li, B.P. Maliakel, E.
Zbii,
1992.561.

7506
12.
Selected physical data for compounds 2-11 [values of
and (250
for
tions in
and
H,
1 H, H-4), 3.73 3 H,
and 2 x H-6’). 4.60 (d. 1 H, H-l),
(c 2); 1.06 9 H,
3.48-3.58 (m, 4 H, H-2, H-4, H-5’, 1 x H-6), 3.69 (s, H,
H-5, 1 x H-6, H-2’. H-3’, H-4’, 2 x H-6’). 4.53
7.23-7.70 25 H, aromatic H). 4:
3.37 3 H, 3.51 3.5
H, H-4), 3.71 (m, 2 H, H-5’ and 1 x H-6’) 3.89-4.28 (m, 5 H, H-3,
2
(c 4);
1.33, 1.35, 1.37, 1.39
9.8 H-2), 3.64 (dd,
10 H. H-3, H-5.2 x H-6, H-2’. H-3’, H-4’.
3 H
2 x
=
3.34
= 3.4 Hz,
1
9.9
3:
6 H, 3 x
1.31, 1.38 (2 3 H each
7.25-7.36
15 H, aromatic
3.32 (s, 3
3.82-4.40 (m, 8
H-3,
= 3.4 Hz, 1 H, H-l), 4.5G4.97 (m, 6 H, 3 x
9.6 Hz, 1 H, H-2). 3.57
= 9.5 Hz, 1
x H-6,2 x H-6’), 4.61-4.97
9 H, 3 x
H). 5:
Hz, 1 H-2), 3.57 (dd,
4.35 (m, 3 H, H-3,2 x H-6), 4.15-4.29 (m, 2 H, 2 x H-6’), 4.52-5.03
H-l, H-2’ and H-4’), 5.40 (dd,
7.2 Hz), 7.24-7.37
15
2.0 Hz,
aromatic
9.6
H-5). 3.96-
H-l, H-4’),
2.2); 2.11 (s, 3 H, A ), 3.37 (s, 3
C
3.53 (dd,
9.6 Hz, 1 H, H-4), 3.76 (m, 1
H-f), 3.89
8 H, 3 x
6:
1
5.91
= 2.0
(c 2);
=
H-3’), 7.25-7.34 (m, 15 aromatic
5.1 Hz, 3 3.36 (m. 1
9.5 Hz, H-4), 3.54 9.6 Hz, H-2), 3.77-4.09
3 x 5.12 (d,
-11.5 (c 3);
= 9.5 Hz, 1
2.78
J
H-4’). 3.38 (s, 3 H,
3.48 (dd,
= 3.6
7
H-3,
2.5
H-5, 2 x H-6, H-S, 2 x H-6’). 4.60
H-3’), 6.58 1 H, 7.22-7.38
). 2.72 (d, J 5.0 Hz, 3 H,
1 H, H-l), 4.55-5.03
15 H, aromatic
3.32 (s, 3 H, 3.86
6
2.07 (s, 3 H,
H-3’), 3.51-
AC
4.30 (m.
H-2, H-3, H-4, H-5,2 x H-6, H-T, 2 x H-6’), 4.56 (d,
3.2 Hz, 1 H, H-l),
(m, 6 H, 3 x
matic H).
5.94
(c 2);
= 9.5 Hz, 1 H, H-4), 6.75 (d, 1
and 2.07 (2 3 H each, 2 x A
NH), X18-7.30 (m, 15 aro-
C
). 1.97-2.09 (2 H more,
3.48-3.62 4 H, H-2, H-4, H-5,
H-5, 1 x H-6 and 4.60
H-4’), 6.90 and 6.98 (2 1 H each, 2 x NH), 7.18-
-21.0 (c 3); 2.13 3 H, A ), 3.40
3.78 H, 3.79-3.97 (m, 6 H,
= 3.2 Hz, 1 H-l),
15 H, aromatic H).
2.08 ), 2.46 (dd,
9.7 Hz, 1 H, H-2), 3.64-3.81 (m, 4 H, H-4,2 x
3.8 Hz, 10.6 1 H,
7 H, H-4’,
and
2.75 (d, J = 4.9 Hz, 3 H,
3.37 (s, 3 H,
3.71-3.79 (m, 2
3.5 Hz, 1
7.30 (m, 15 aromatic H). MP
(s, 3 H, 3.42-3.60 4 H, H-2, H-4, H-S,
H-3, H-5.2 x H-6, H-3’,
H-3, 1 x H-6), 3.92-4.12
4.63-5.02 (m, 7 3 x
3
=
C
4.61 (d,
(m, 6 3 x
-32.2 (c 2.5);
5.66
1.99
(dd,
(dd,
=
8.8
= 4.0 Hz,
3
1 H, H-4’), 7.25-7.35
=
14.3 Hz, 1 H,
3.55 = 3.5 Hz,
9.7 Hz, 1 H, H-3). 4.16
2.1 Hz, 1 H,
aromatic H), 7.61
(2 3 H each, 2 x A ), 2.12
3
AC
= 11 Hz, 1 H,
3.37
H-6, H-S), 3.99
4.27
3 x
1 H, H-5). 4.36
7.25-7.36
=
4.66
J = 5.8
14.9 Hz,
3.42-3.55
1 H,
1 I-I, H-l), 4.63-5.01
1 Ii, NH). 11:
5.1 Hz, 1 H,
15
(c 2.9);
2.24 (dd,
C
= 4.1 Hz, 1 H,
3.74-3.83
4.22 (dd,
3.38 (s, 3 H,
2 H, H-5,
2.9 Hz,
4 H, H-2, H-4.2 x H-6). 3.71 (s, 3 H,
4.04 (dd, 9.3
4.58-5.03 (m, 8 H, H-l, H-4’, 3 x
3.95
1
= 12.1 Hz, 1 H,
6.06 J = 6.8 Hz, 1
7.21-7.33 (m, 15 H, aromatic
13.
Vlahov, P.I. Vlahova, R.R. Schmidt publication in preparation.
(Received in Germany 24 July 1992)