158
2
General Synthetic Methods
⊡ Scheme 69
Oxidative deprotection of p-methoxybenzylglycoside
A remarkable rate difference in the hydrogenolysis of α- and β-benzyl D-gluco-and D-galactopyranosides has been reported, with the β-anomers being more readily cleavable [395]. Ferric chloride has been employed for anomeric debenzylation in oligosaccharides [18].
Methoxy-substituted benzyl glycosides have been used as precursors for reducing sugars [396]. As mentioned in > Sect. 2.1.3 under > “p-Methoxy Benzyl (PMB) Ethers”, their
utility lies in the fact that they are more readily cleaved oxidatively than the unsubstituted
benzyl ethers ( > Scheme 69). All these transformations have great synthetic value although
the process is not regioselective since it is operational for all the benzyloxy groups present in
the sugar.
Particularly useful in protecting the anomeric hydroxyl are those substituted benzyl groups that
are light-sensitive. Such groups are stable to a wide variety of chemical treatments and at the
same time are sensitive to irradiation under conditions that leave other functional groups in the
molecule unaffected. Thus, 2-nitro benzyl and 3,4-dimethoxy-6-nitrobenzyl (6-nitroveratryl)
glycosides are more stable to acid hydrolysis than are the corresponding benzyl glycosides but
are readily photolyzed at 320 nm to the reducing sugars in high yields ( > Scheme 70) [397].
In this context photocleavable linkers for solid-phase synthesis, based on the lability of 2-nitro
benzyl moieties under irradiation, have been applied to the liberation of the anomeric center
in oligosaccharides [398].
Other substituted-benzyl glycosides that can be selectively removed in the presence of unsubstituted benzyl ethers have been developed. For example, 2-(hydroxycarbonyl)benzyl glycosides are easily sovolyzed by treatment with Tf 2 O in the presence of di-tert-butylmethylpyridine (DBMP). The reaction implies anomeric C–O bond cleavage since it takes place
by lactonization via the mixed anhydride to generate phthalide and the oxocarbenium ion
( > Scheme 71) [399].
⊡ Scheme 70
Example of light-sensitive glycosides: 2-nitrobenzyl and 6-nitroveratryl glycosides
2
General Synthetic Methods
⊡ Scheme 69
Oxidative deprotection of p-methoxybenzylglycoside
A remarkable rate difference in the hydrogenolysis of α- and β-benzyl D-gluco-and D-galactopyranosides has been reported, with the β-anomers being more readily cleavable [395]. Ferric chloride has been employed for anomeric debenzylation in oligosaccharides [18].
Methoxy-substituted benzyl glycosides have been used as precursors for reducing sugars [396]. As mentioned in > Sect. 2.1.3 under > “p-Methoxy Benzyl (PMB) Ethers”, their
utility lies in the fact that they are more readily cleaved oxidatively than the unsubstituted
benzyl ethers ( > Scheme 69). All these transformations have great synthetic value although
the process is not regioselective since it is operational for all the benzyloxy groups present in
the sugar.
Particularly useful in protecting the anomeric hydroxyl are those substituted benzyl groups that
are light-sensitive. Such groups are stable to a wide variety of chemical treatments and at the
same time are sensitive to irradiation under conditions that leave other functional groups in the
molecule unaffected. Thus, 2-nitro benzyl and 3,4-dimethoxy-6-nitrobenzyl (6-nitroveratryl)
glycosides are more stable to acid hydrolysis than are the corresponding benzyl glycosides but
are readily photolyzed at 320 nm to the reducing sugars in high yields ( > Scheme 70) [397].
In this context photocleavable linkers for solid-phase synthesis, based on the lability of 2-nitro
benzyl moieties under irradiation, have been applied to the liberation of the anomeric center
in oligosaccharides [398].
Other substituted-benzyl glycosides that can be selectively removed in the presence of unsubstituted benzyl ethers have been developed. For example, 2-(hydroxycarbonyl)benzyl glycosides are easily sovolyzed by treatment with Tf 2 O in the presence of di-tert-butylmethylpyridine (DBMP). The reaction implies anomeric C–O bond cleavage since it takes place
by lactonization via the mixed anhydride to generate phthalide and the oxocarbenium ion
( > Scheme 71) [399].
⊡ Scheme 70
Example of light-sensitive glycosides: 2-nitrobenzyl and 6-nitroveratryl glycosides