430
3
Chemical Glycosylation Reactions
Et
ethyl
Me
methyl
MS
molecular sieves
NBS N-bromosuccinimide
NIS
N-iodosuccinimide
Ph
phenyl
i-Pr
isopropyl
PPTS pyridinium p-toluenesulfonate
Pv
pivaloyl
TBAF tetrabutylammonium fluoride
TBAI tetrabutylammonium iodide
TEA triethylamine
Tf
trifluoromethanesulfonyl
THF tetrahydrofuran
TMS trimethylsilyl
TMU 1,1,3,3-tetramethylurea
Tr
triphenylmethyl
Ts
toluenesulfonyl
1 Chemical Glycosylation of Glycosyl Bromide and Chloride
The use of glycosyl bromide or chloride as an effective glycosyl donor in the glycosylation
reaction was first introduced by Koenigs and Knorr in 1901 [1]. In relation to the anomeric stereochemistry of the glycosylation reaction, three significant basic methods, (1) the
neighboring group assisted method for construction of 1,2-trans glycosides such as β-glucoor α-manno type glycoside, (2) the in-situ anomerization method for synthesis of α-gluco or α-manno type glycoside [2], and (3) the heterogenic catalyst method for preparation of
β-mannoglycoside [3], were developed in this area [4d, f]. The well-known classical Koenigs–
Knorr method used heavy metal salts (mainly silver and mercury salts) as activating reagents
as summarized in > Table 1. A variety of heavy metal salts such as AgClO 4 , AgOTf, AgNO 3 ,
Ag 2 CO 3 , Ag 2 O, Ag-silicate, Hg(CN) 2 , HgBr 2 , HgCl 2 , and HgI 2 [5] and their combined use
were employed in this area [4a–h, j, l]. The order of reactivity of some representative catalysts
was generally confirmed [4d, f]. Furthermore, Ag 2 CO 3 , Ag 2 O, HgO, CdCO 3 , S-collidine,
and TMU were frequently used as an acid scavenger, and water was generally removed by
Drierite ® and molecular sieves during these glycosylation reactions [4a–h, j, l].
On the other hand, other glycosylation methods using glycosyl bromide or chloride in the
absence of any metal were also widely studied. Lemieux et al. [6] introduced a mild glycosylation method in the presence of Bu 4 NBr. Also, the glycosylation protocols which involved
a transformation of glycosyl bromide into the corresponding onium salts by Et 3 N, Ph 3 P, and
Me 2 S were developed by Schuerch et al. [7]. Furthermore, the uses of other activating reagents
without heavy metals and including several Lewis acids such as SnCl 4 [8], BF 3 Et 2 O [8],
Sn(OTf) 2 -collidine [9a], Sn(OTf) 2 -TMU [9b], TrCl-ZnCl 2 [10], LiClO 4 [11], I 2 -DDQ [12],
3
Chemical Glycosylation Reactions
Et
ethyl
Me
methyl
MS
molecular sieves
NBS N-bromosuccinimide
NIS
N-iodosuccinimide
Ph
phenyl
i-Pr
isopropyl
PPTS pyridinium p-toluenesulfonate
Pv
pivaloyl
TBAF tetrabutylammonium fluoride
TBAI tetrabutylammonium iodide
TEA triethylamine
Tf
trifluoromethanesulfonyl
THF tetrahydrofuran
TMS trimethylsilyl
TMU 1,1,3,3-tetramethylurea
Tr
triphenylmethyl
Ts
toluenesulfonyl
1 Chemical Glycosylation of Glycosyl Bromide and Chloride
The use of glycosyl bromide or chloride as an effective glycosyl donor in the glycosylation
reaction was first introduced by Koenigs and Knorr in 1901 [1]. In relation to the anomeric stereochemistry of the glycosylation reaction, three significant basic methods, (1) the
neighboring group assisted method for construction of 1,2-trans glycosides such as β-glucoor α-manno type glycoside, (2) the in-situ anomerization method for synthesis of α-gluco or α-manno type glycoside [2], and (3) the heterogenic catalyst method for preparation of
β-mannoglycoside [3], were developed in this area [4d, f]. The well-known classical Koenigs–
Knorr method used heavy metal salts (mainly silver and mercury salts) as activating reagents
as summarized in > Table 1. A variety of heavy metal salts such as AgClO 4 , AgOTf, AgNO 3 ,
Ag 2 CO 3 , Ag 2 O, Ag-silicate, Hg(CN) 2 , HgBr 2 , HgCl 2 , and HgI 2 [5] and their combined use
were employed in this area [4a–h, j, l]. The order of reactivity of some representative catalysts
was generally confirmed [4d, f]. Furthermore, Ag 2 CO 3 , Ag 2 O, HgO, CdCO 3 , S-collidine,
and TMU were frequently used as an acid scavenger, and water was generally removed by
Drierite ® and molecular sieves during these glycosylation reactions [4a–h, j, l].
On the other hand, other glycosylation methods using glycosyl bromide or chloride in the
absence of any metal were also widely studied. Lemieux et al. [6] introduced a mild glycosylation method in the presence of Bu 4 NBr. Also, the glycosylation protocols which involved
a transformation of glycosyl bromide into the corresponding onium salts by Et 3 N, Ph 3 P, and
Me 2 S were developed by Schuerch et al. [7]. Furthermore, the uses of other activating reagents
without heavy metals and including several Lewis acids such as SnCl 4 [8], BF 3 Et 2 O [8],
Sn(OTf) 2 -collidine [9a], Sn(OTf) 2 -TMU [9b], TrCl-ZnCl 2 [10], LiClO 4 [11], I 2 -DDQ [12],