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Scheme 2 Iron(
III
) chloride debenzylations. Phth
=
Phthaloyl.
OH
OH
H
2
SO
4
O
O
H
HO
H
HO
MeOH
OH
OH
OH
OMe
8
9
8
10
D
-glucose
D
-galactose
FeCl
3
(1 equiv)
MeOH
rt
60 °C
HO
HO
O
HO
OH
O
OMe
OMe
HO
OH
OH
HO
11
12
, 75%
, 75%
Scheme 3 Fischer glycosylation and Lubineau-Fischer ferric chloride version.
quite challenging for the one-step chemical synthesis of glycosides when
the amount of the nucleophile is limited.
17
A century later, Andr´
Lubineau and Jean-Claude Fischer replaced the protic acid by a Lewis acid.
18
Strikingly, treatment of
D
-glucose and
D
-galactose with ferric chloride
(1 equiv) in methanol at room temperature (
D
-glucose) or 60 1C(
D
-galac-
tose) gave the corresponding methyl
D
-furanosides 11 and 12 in 75% yield,
instead of the thermodynamically more stable pyranosides (Scheme 3).
Iron(
III
)-sugar complexes apparently prevent ring expansion to the
more stable anomers. This one-step preparation of furanosides from the
unprotected hexoses was instrumental in the development of synthetic
routes leading to important bio-relevant targets. Some representative
reports that rely on the use of this unique transformation are presented
below. First, Plusquellec and co-workers modified this version to a
practical glycosylation using only 1.5 equiv of simple alcohols in THF or
1,4-dioxane as solvents with
D
-glucose,
D
-galactose,
D
-mannose and
D
-galacturonic acid (Scheme 4).
19
Currently this reaction is often the starting point in the multi-
step synthesis of hexofuranoside-containing bioactive targets. Thus,
galactose was converted to anomeric methyl furanosides 12 via this ferric
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