Glycosyl Trichloroacetimidates
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493
the Wong group [164]; biological studies exhibited growth inhibition of vancomycin sensitive
bacteria by several of these compounds.
N-Glycopeptides are generally obtained by treatment of reducing sugars with ammonium
bicarbonate [165] or reduction of glycosyl azides [166] with activated aspartic acid. This way
a heptasaccharide synthesized with O-glycosyl trichloroacetimidates as donors was linked to
Asp [167,168,169,170]; further work along these lines was carried out [171]. Direct formation of the N-glycosidic linkage with Asn by chemical glycosylation is still an important task.
An interesting method was investigated by Ito et al. [172] based on hydroxyamination of the
Asp side chain and then glycosylation with a glycosyl donor. The results show, for standard
glycosyl donors direct N- glycosylation is possible, however so far yields and anomeric stereoselection are not yet satisfactory.
A number of C- and N-linked tryptophan glycoconjugates were discovered as constituents
of natural products [173,174,175,176]. Also tryptophan N-glucoside 27d has been detected
for which Unverzagt et al. [177] reported a successful synthesis ( > Scheme 27). With the
help of 2-O-pivaloyl protection in glucosyl donor 27a the undesired acetal formation could be
overcome; thus with acceptor 27b N-glucoside 27c could be obtained and then transformed
into target molecule 27d.
5.3 Nucleoside and Nucleotide Glycosidation
The presence of carbohydrate moieties in biomolecules influences many biological functions,
thus also modulation of the functions of the aglycone. Therefore, studies have been undertaken
to glycosylate nucleosides [178] and nucleotides [179]. Particularly interesting is the direct
glycosylation of CPG-bound oligo-deoxynucleotides containing pyrimidine residues leading
to reaction preferentially at the 5 -end.
The occurrence at 5-(β-D-glucopyranosyloxymethyl-2 -deoxyuridine (βdJ) in DNA, for
instance of Trypanosoma brucei [180,181,182], led to the development of an efficient route
for the synthesis of βdJ ( > Scheme 28) and its phosphoramidite as building blocks for DNA
synthesis [183]. The synthesis was based on glucosyl donor 28a (R = R = Bz) which gave
with acceptor 28b intermediate 28cβ and after deprotection βdJ. Similarly, from 28a (R = Bn,
R = Ac) and 28b α-linked 28cα was obtained which led to αdJ.
5.4 Synthesis of Glycosaminoglycans
Glycosaminoglycans (GAGs) are bioactive oligosaccharides that are highly functionalized, linear, and anionically charged. Because of their complexity their chemical synthesis is a demanding task. The chondroitin sulfates (CSs) are a member of the GAG family. They are found in
the extracellular matrix of connective tissues at the surface of many cells and in intracellular
secretory granules [184,185]. They are linear heteroglycans built mainly from D-GlcA and
GalNAc dimers which are β(1–3)-linked; chain extension employs a β(1–4)-linkage. In addition, the sugar residues are sulfated at various positions (→ A- E- and K-type CSs). Stereocontrolled shark cartilage CS (D-type) synthesis has been successfully carried out by Jacquinet et
al. ( > Scheme 29) [186,187]. The GlcA building block 29a possesses as temporary protecting
group for chain extension at 4-O the chloroacetyl group, and for sulfation at 2-O the benzoyl
3.2
493
the Wong group [164]; biological studies exhibited growth inhibition of vancomycin sensitive
bacteria by several of these compounds.
N-Glycopeptides are generally obtained by treatment of reducing sugars with ammonium
bicarbonate [165] or reduction of glycosyl azides [166] with activated aspartic acid. This way
a heptasaccharide synthesized with O-glycosyl trichloroacetimidates as donors was linked to
Asp [167,168,169,170]; further work along these lines was carried out [171]. Direct formation of the N-glycosidic linkage with Asn by chemical glycosylation is still an important task.
An interesting method was investigated by Ito et al. [172] based on hydroxyamination of the
Asp side chain and then glycosylation with a glycosyl donor. The results show, for standard
glycosyl donors direct N- glycosylation is possible, however so far yields and anomeric stereoselection are not yet satisfactory.
A number of C- and N-linked tryptophan glycoconjugates were discovered as constituents
of natural products [173,174,175,176]. Also tryptophan N-glucoside 27d has been detected
for which Unverzagt et al. [177] reported a successful synthesis ( > Scheme 27). With the
help of 2-O-pivaloyl protection in glucosyl donor 27a the undesired acetal formation could be
overcome; thus with acceptor 27b N-glucoside 27c could be obtained and then transformed
into target molecule 27d.
5.3 Nucleoside and Nucleotide Glycosidation
The presence of carbohydrate moieties in biomolecules influences many biological functions,
thus also modulation of the functions of the aglycone. Therefore, studies have been undertaken
to glycosylate nucleosides [178] and nucleotides [179]. Particularly interesting is the direct
glycosylation of CPG-bound oligo-deoxynucleotides containing pyrimidine residues leading
to reaction preferentially at the 5 -end.
The occurrence at 5-(β-D-glucopyranosyloxymethyl-2 -deoxyuridine (βdJ) in DNA, for
instance of Trypanosoma brucei [180,181,182], led to the development of an efficient route
for the synthesis of βdJ ( > Scheme 28) and its phosphoramidite as building blocks for DNA
synthesis [183]. The synthesis was based on glucosyl donor 28a (R = R = Bz) which gave
with acceptor 28b intermediate 28cβ and after deprotection βdJ. Similarly, from 28a (R = Bn,
R = Ac) and 28b α-linked 28cα was obtained which led to αdJ.
5.4 Synthesis of Glycosaminoglycans
Glycosaminoglycans (GAGs) are bioactive oligosaccharides that are highly functionalized, linear, and anionically charged. Because of their complexity their chemical synthesis is a demanding task. The chondroitin sulfates (CSs) are a member of the GAG family. They are found in
the extracellular matrix of connective tissues at the surface of many cells and in intracellular
secretory granules [184,185]. They are linear heteroglycans built mainly from D-GlcA and
GalNAc dimers which are β(1–3)-linked; chain extension employs a β(1–4)-linkage. In addition, the sugar residues are sulfated at various positions (→ A- E- and K-type CSs). Stereocontrolled shark cartilage CS (D-type) synthesis has been successfully carried out by Jacquinet et
al. ( > Scheme 29) [186,187]. The GlcA building block 29a possesses as temporary protecting
group for chain extension at 4-O the chloroacetyl group, and for sulfation at 2-O the benzoyl