700
3
Chemical Glycosylation Reactions
Abbreviations
AIBN
azobisisobutyronitrile
DBU
1,8-diazabicyclo[5.4.0]undec-7-ene
HMPA
hexamethylphosphoramide
HSAB
hard and soft acids and bases
LAH
lithium aluminum hydride
LDA
lithium diisopropylamide
m-CPBA
3-chloroperbenzoic acid
NIS
N-iodosuccinimide
THF
tetrahydrofuran
TMSBr
trimethylsilyl bromide
1 Introduction
Monosaccharides possessing a double bond between C1 and C2 are known under their trivial name as glycals. The name glycals was coined after the product of the first synthesis of
1,2-unsaturated sugar from D-glucose 1 which was named D-glucal [1]. Consequently, the
generic name “glycals” was adopted for this class of unsaturated sugars, which are in fact
extensively substituted cyclic vinyl ethers. Such cyclic vinyl ethers are also encountered as
structural motifs in total synthesis of some complex natural products [2,3].
Systematic naming [4,5] uses alditol descriptors and not the parent aldose, as is the case in
commonly used trivial names. Thus, 4 should be named 1,5-anhydro-2-deoxy-D-arabino-hex1-enitol. However, trivial names are being widely used because of their simplicity. Advances
in the synthesis of glycals have been summarized regularly in comprehensive reviews [2,6,7,8]
and new reactions were regularly summarized in annual reports [9]. Recent developments in
the chemistry of glycals have expanded their importance as useful organic substrates and intermediates far beyond the limits set by the traditional placement of somewhat esoteric unsaturated sugars. Glycals are extensively used as glycosylating agents, [10,11,12] especially in the
synthesis of 2-deoxy sugars [13,14,15,16] and oligosaccharides [17], and also as precursors of
C-glycosyl compounds [18,19,20]. They are also widely recognized as versatile chiral building blocks [21,22,23]. Selectively protected glycals are being used in chemical and enzymatic
synthesis of complex carbohydrates and in the synthesis of C-oligosaccharides and glycoproteins [24,25]. There is an increased interest in exploring carbohydrate scaffolds in drug discovery as a consequence of identifying the role of glycoconjugates in biological recognition and
signal transduction processes [26]. After genomics and proteomics, glycomics appears to be
the next significant frontier for the development of new medical therapeutics, where progress
will require concerted multidisciplinary efforts. Specifically, chemical glycomics will require
the maturation of synthetic carbohydrate methodologies that would allow the preparation of
glycoconjugates in a parallel, automated synthesis [27,28]. It now appears that unsaturated
sugar derivatives, like glycals, can be used as useful substrates for such a purpose [29,30].
Various aspects of essential glycal chemistry connected to Ferrier rearrangement and anomeric
carbanions have been extensively reviewed [31,32,33,34].
3
Chemical Glycosylation Reactions
Abbreviations
AIBN
azobisisobutyronitrile
DBU
1,8-diazabicyclo[5.4.0]undec-7-ene
HMPA
hexamethylphosphoramide
HSAB
hard and soft acids and bases
LAH
lithium aluminum hydride
LDA
lithium diisopropylamide
m-CPBA
3-chloroperbenzoic acid
NIS
N-iodosuccinimide
THF
tetrahydrofuran
TMSBr
trimethylsilyl bromide
1 Introduction
Monosaccharides possessing a double bond between C1 and C2 are known under their trivial name as glycals. The name glycals was coined after the product of the first synthesis of
1,2-unsaturated sugar from D-glucose 1 which was named D-glucal [1]. Consequently, the
generic name “glycals” was adopted for this class of unsaturated sugars, which are in fact
extensively substituted cyclic vinyl ethers. Such cyclic vinyl ethers are also encountered as
structural motifs in total synthesis of some complex natural products [2,3].
Systematic naming [4,5] uses alditol descriptors and not the parent aldose, as is the case in
commonly used trivial names. Thus, 4 should be named 1,5-anhydro-2-deoxy-D-arabino-hex1-enitol. However, trivial names are being widely used because of their simplicity. Advances
in the synthesis of glycals have been summarized regularly in comprehensive reviews [2,6,7,8]
and new reactions were regularly summarized in annual reports [9]. Recent developments in
the chemistry of glycals have expanded their importance as useful organic substrates and intermediates far beyond the limits set by the traditional placement of somewhat esoteric unsaturated sugars. Glycals are extensively used as glycosylating agents, [10,11,12] especially in the
synthesis of 2-deoxy sugars [13,14,15,16] and oligosaccharides [17], and also as precursors of
C-glycosyl compounds [18,19,20]. They are also widely recognized as versatile chiral building blocks [21,22,23]. Selectively protected glycals are being used in chemical and enzymatic
synthesis of complex carbohydrates and in the synthesis of C-oligosaccharides and glycoproteins [24,25]. There is an increased interest in exploring carbohydrate scaffolds in drug discovery as a consequence of identifying the role of glycoconjugates in biological recognition and
signal transduction processes [26]. After genomics and proteomics, glycomics appears to be
the next significant frontier for the development of new medical therapeutics, where progress
will require concerted multidisciplinary efforts. Specifically, chemical glycomics will require
the maturation of synthetic carbohydrate methodologies that would allow the preparation of
glycoconjugates in a parallel, automated synthesis [27,28]. It now appears that unsaturated
sugar derivatives, like glycals, can be used as useful substrates for such a purpose [29,30].
Various aspects of essential glycal chemistry connected to Ferrier rearrangement and anomeric
carbanions have been extensively reviewed [31,32,33,34].