4
46
P. Florio et al. / Carbohydrate Research 328 (2000) 445–448
1
potentially more metabolically stable gly-
coside [7], and depending upon the aglycon,
may be more robust towards acid hydrolysis
structure 7 , fulfills this criterion. The key
intermediate is the a-glucuronyl bromide,
methyl 2,3,4-tri-O-acetyl-a- -glucopyranosy-
D
[8] than the corresponding O-glycosides. A
luronate bromide (6) [10], which can be read-
ily prepared in three steps from lactone 5
(Scheme 1).
glycosyl amine provides ready access to a
range of relatively stable acylated species at
the anomeric position. Both these alternate
forms of the sialylmimetic 1 allow for the
introduction of significant structural variation
in the moiety that replaces the C-6 glycerol
side chain of the sialic acids.
The glucuronyl bromide 6 is a convenient
starting material for either O- or S-glu-
curonide synthesis. Accordingly, 1 could be
synthesized in just three steps from the bro-
mide 6 (glycosidation, b-elimination and
saponification) in a moderate 38% yield, and
in 27% overall yield from -glucurono-6,3-lac-
D
tone (5). Glycosidation of 6 with 2-propanol,
carried out using Ag CO as catalyst in the
2
3
presence of 3 A molecular sieves, proceeded to
,
give the b anomer exclusively in excellent
85%) yield. While the overall yield for the
synthesis of 1 was comparable to that ob-
tained (30%) in nine steps from -glucose via
(
D
The previously reported syntheses [6] of the
uronic acid derivatives 1 and 2 were via selec-
tive Pt(0) oxidation of the primary hydroxyl
the previous pathway [6], the ease of conver-
sion (two steps) to the target compound 1
after glycosidation (compared with six steps in
the previous pathway) more than compensates
for the moderate yield obtained.
group of the corresponding isopropyl b- -glu-
D
copyranosides. For the development of a
4
wider range of D -uronic acid-based mimetics,
The introduction of the aglycon moiety di-
rectly into the glucuronate is particularly at-
tractive for the synthesis of 1-thiopyrano-
siduronates not readily accessible via the oxi-
dative pathway. Alkyl 1-thioglucuronides have
previously been prepared from the a-glu-
curonyl bromide 6 in moderate yields, either
by reaction with a potassium thiolate formed
in methanol at low temperature [11] or by
synthesis and subsequent thermal rearrange-
ment of O-alkyl S-glucuronyl xanthates [12].
In this work, we required a versatile entry
point into a range of thioglucuronides and for
this chose the glucuronyl b-thiolacetate
derivative 8. This compound has the potential
for the thiol functionality to be selectively
unmasked for coupling to a range of alkyl
halides, as has previously been reported for a
number of anomeric thioacetylated carbohy-
drates [13–15]. The b-thiolacetate derivative 8
could be prepared in 78% yield by reaction of
the a-glucuronyl bromide 6 with KSAc in
acetone (Scheme 2). Selective S-deacetylation
including those containing a thioglycoside that
are not readily accessible via the Pt(0) oxida-
tive pathway [9], an approach in which the
aglycon is introduced directly into the glu-
curonate was sought. This would avoid taking
the aglycon through the oxidation and esterifi-
cation steps of the previous pathway. A syn-
thetic approach starting from
D-glucurono-
6,3-lactone (5), to compounds of the general
Scheme 1. Reagents and conditions: (a) i. NaOMe, MeOH, rt,
6
5
h; ii. Ac O, HClO , 4 °C–rt, overnight; (b) HBr, AcOH,
°C, overnight.
2
4
of 8 using Et NH [13] and subsequent reaction
2
with 2-bromopropane produced a mixture of
1
the 1-thio-b- -glucuronide 9 and the corre-
D
All new compounds were fully characterized and gave
satisfactory spectral and analytical data.
sponding eliminated derivative 10 after
Florio, Pas
