Degradations and Rearrangement Reactions
2.7
377
2 Hydrolysis of Glycosides and Polysaccharides
Among all the degradation patterns for glycosides and polysaccharides, hydrolysis is the most
important process in carbohydrate chemistry, either in nature or in biological systems. Before
long, it became a process important in the food industry for production of free sugars and is
now gaining more and more attention because of the present energy crisis. This is because
petroleum is not an ideal chemical feedstock for industry, due to its intractability, while glycosides and polysaccharides—which are abundant and recyclable—can be utilized in the production of fuel and chiral synthons to be used instead of traditional petroleum [6].
2.1 Chemical Hydrolysis
Chemical hydrolysis is a very familiar reaction for the sugar industry. However, it may generate
an array of possible degradation products. For example, very low rate constants for the spontaneous hydrolysis of nonactivated methyl β-D-glucopyranoside 1 have been determined at
220 °C [7], ( > Fig. 1). At pH > 7, the rate constants approach a constant value. On hydrolysis
at pH 10 in the presence of H 2
18 O, the results show that the reaction occurs almost exclusively by cleavage of the C1/O1 bond. The β-anomer 1 is roughly twice as reactive as the
α-anomer 2, as are also the anomeric pair of methyl D-ribofuranosides 3 and 4. Unlike the
hydrolysis at pH < 7, the hydrolysis of 1 without catalysts proceeds with a negative entropy of
activation. This is consistent with bimolecular attack of water on 1.
Acid hydrolysis of isopropenyl α-D-glucopyranoside 5 at pH 3.0 and 25 °C occurs by C-protonation followed by cleavage of the alkenyl ether C/O bond. The α-anomer 5 is hydrolyzed
4.5-times faster that its β-anomer 6. Spectroscopic evidence indicates greater conjugation of
O1 with the double bond, and hence a greater basicity of the β-carbon of the double bond, in 5
compared to 6 [8].
An accelerating effect by the intramolecular nucleophilic catalysis of a phosphate anion upon
hydrolysis of the phosphate 7 at 80TT °C and pH 6–9, in comparison with the unsubstituted 8
and its 2-O-methyl derivatives 9, has been observed [9]. The reaction of 8 is base-catalyzed
down almost to pH 7, while that of 9 is pH-independent up to pH 9–10 The hydrolysis of 7
proceeds about 100-times faster than that of 9 at pH ∼9 and 80 °C. In comparison, the hydrolysis of 10 is pH-independent down to pH 7 and ∼20-times slower than that of 7 at pH 9 and
80 °C [10].
A kinetic study of the acyl migration reaction of the 1-O-acyl β-D-glucopyranuronic acid 11,
a model drug ester glucuronide, employing a directly coupled stop-flow HPLC/600 MHz
1 H-NMR system at pH 7.4 and 25 °C, has been carried out [11]. The acyl migration rate of the
β-1-O-acyl group of 11 is greater than any other regio-isomers. The simulating mutarotation
rates for the 4-O-acyl isomers 12 are in good accord with the experimental values.
The fructofuranosyl cation 13 is the first formed product of the acid-catalyzed melt thermolyses of sucrose 14 ( > Scheme 1). This reacts with hydroxy nucleophiles co-existing in the melt
to give fructose-grafted products. Rigorous thermolysis of 14 itself at 170 °C furnishes a fructosylglucan with an average dp ∼25 together with the known sucrose thermal oligosaccharides
from 14, such as 15 (3.9%) and 16 (4.1%) [12].
Mechanistic studies on acid hydrolysis of glycosides often encounter the endo/exo-cyclic
cleavage problem [13]. For instance, the sulfuric acid (1%)-catalyzed acetolysis of the
2.7
377
2 Hydrolysis of Glycosides and Polysaccharides
Among all the degradation patterns for glycosides and polysaccharides, hydrolysis is the most
important process in carbohydrate chemistry, either in nature or in biological systems. Before
long, it became a process important in the food industry for production of free sugars and is
now gaining more and more attention because of the present energy crisis. This is because
petroleum is not an ideal chemical feedstock for industry, due to its intractability, while glycosides and polysaccharides—which are abundant and recyclable—can be utilized in the production of fuel and chiral synthons to be used instead of traditional petroleum [6].
2.1 Chemical Hydrolysis
Chemical hydrolysis is a very familiar reaction for the sugar industry. However, it may generate
an array of possible degradation products. For example, very low rate constants for the spontaneous hydrolysis of nonactivated methyl β-D-glucopyranoside 1 have been determined at
220 °C [7], ( > Fig. 1). At pH > 7, the rate constants approach a constant value. On hydrolysis
at pH 10 in the presence of H 2
18 O, the results show that the reaction occurs almost exclusively by cleavage of the C1/O1 bond. The β-anomer 1 is roughly twice as reactive as the
α-anomer 2, as are also the anomeric pair of methyl D-ribofuranosides 3 and 4. Unlike the
hydrolysis at pH < 7, the hydrolysis of 1 without catalysts proceeds with a negative entropy of
activation. This is consistent with bimolecular attack of water on 1.
Acid hydrolysis of isopropenyl α-D-glucopyranoside 5 at pH 3.0 and 25 °C occurs by C-protonation followed by cleavage of the alkenyl ether C/O bond. The α-anomer 5 is hydrolyzed
4.5-times faster that its β-anomer 6. Spectroscopic evidence indicates greater conjugation of
O1 with the double bond, and hence a greater basicity of the β-carbon of the double bond, in 5
compared to 6 [8].
An accelerating effect by the intramolecular nucleophilic catalysis of a phosphate anion upon
hydrolysis of the phosphate 7 at 80TT °C and pH 6–9, in comparison with the unsubstituted 8
and its 2-O-methyl derivatives 9, has been observed [9]. The reaction of 8 is base-catalyzed
down almost to pH 7, while that of 9 is pH-independent up to pH 9–10 The hydrolysis of 7
proceeds about 100-times faster than that of 9 at pH ∼9 and 80 °C. In comparison, the hydrolysis of 10 is pH-independent down to pH 7 and ∼20-times slower than that of 7 at pH 9 and
80 °C [10].
A kinetic study of the acyl migration reaction of the 1-O-acyl β-D-glucopyranuronic acid 11,
a model drug ester glucuronide, employing a directly coupled stop-flow HPLC/600 MHz
1 H-NMR system at pH 7.4 and 25 °C, has been carried out [11]. The acyl migration rate of the
β-1-O-acyl group of 11 is greater than any other regio-isomers. The simulating mutarotation
rates for the 4-O-acyl isomers 12 are in good accord with the experimental values.
The fructofuranosyl cation 13 is the first formed product of the acid-catalyzed melt thermolyses of sucrose 14 ( > Scheme 1). This reacts with hydroxy nucleophiles co-existing in the melt
to give fructose-grafted products. Rigorous thermolysis of 14 itself at 170 °C furnishes a fructosylglucan with an average dp ∼25 together with the known sucrose thermal oligosaccharides
from 14, such as 15 (3.9%) and 16 (4.1%) [12].
Mechanistic studies on acid hydrolysis of glycosides often encounter the endo/exo-cyclic
cleavage problem [13]. For instance, the sulfuric acid (1%)-catalyzed acetolysis of the