L. F. Bornaghi, S.-A. Poulsen / Tetrahedron Letters 46 (2005) 3485–3488
3487
Table 3. Microwave-accelerated Fischer glycosylations of N-acetyl-D-glucosamine, N-acetyl-D-galactosamine, D-glucose, D-galactose and
D-mannose in various alcohols
Entry
Solvent
Starting material
Temperature (°C)
a/b Ratioa
1
Methanol
Methanol
Ethanol
N-Acetyl-D-glucosamine
90
120
120
120
5.0/1
13.0/1
10.6/1
8.9/1
2
3
4
5Benzyl alcohol
Benzyl alcohol
0
15
10.3/1
6
7
8
Benzyl alcohol
Allyl alcohol
Allyl alcohol
200
120
150
Decomposition
12.7/1
Decomposition
9
Methanol
Methanol
N-Acetyl-D-galactosamine
90
120
120
150
120
Only a
Only a
Only a
Only a
Only a
10
11
12
13
Benzyl alcohol
Benzyl alcohol
Allyl alcohol
14
15Methanol
Methanol
D-Glucose
120
90
10.0/1
b
.1/1
15
16
17
18
Benzyl alcohol
Benzyl alcohol
Allyl alcohol
120
150
120
7.6/1
9.0/1
8.3/1
19
20
21
22
23
Methanol
Methanol
D-Galactose
90
120
120
150
120
9.3/1
12.0/1
7.0/1
Benzyl alcohol
Benzyl alcohol
Allyl alcohol
10.6/1
9.7/1
24
25Methanol
Methanol
D-Mannose
120
90
6.1/1
9.8/1
26
27
28
Benzyl alcohol
Benzyl alcohol
Allyl alcohol
120
150
120
6.9/1
10.2/1
7.7/1
a Anomeric composition of reaction mixture was monitored by 1H NMR spectroscopy, following microwave irradiation for 10 min.
b Reaction performed on 0.5g (0.0027 mol) scale to provide 0.39 g of purified product after recrystallisation (74%). 10
We have applied microwave irradiation to conventional
Fischer glycosylation resulting in an impressive acceler-
ation of reaction time (minutes compared to hours)
with good a-glycoside product selectivity. The synthesis
is both practical and efficient for each substrate
(N-acetyl-D-glucosamine, N-acetyl-D-galactosamine, D-
glucose, D-galactose and D-mannose). This study dem-
onstrates that microwave irradiation has potential as
one of the easiest and quickest routes to prepare simple
glycosides using Fischer glycosylation. Microwave
equipment with scale-up capabilities (automated reac-
tion handling modules or continuous flow through sys-
tems) is commercially available to support the transfer
from feasibility studies to large-scale synthesis with
either minimal or no need for further optimisation. This
equipment will allow synthesis on a multigram or even
kilogram scale. A larger investigation of various glyco-
sylation reactions and sugar protecting group manipul-
ations using microwave irradiation is underway.
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We thank Professor I. Jenkins and Dr J. Ripper for their
helpful discussions and for the opportunity to use their
microwave oven. We thank the Australian Research
Council for financial assistance.