Chemoselective Synthesis of Oligosaccharides of 2-Deoxy-2-aminosugars

Abstract

Along with the application of the S-benzoxazolyl glycosides to the high-yielding synthesis of disaccharides of the 2-amino-2-deoxy series, chemoselective assembly of oligosaccharides containing multiple residues of 2-amino-2-deoxyglycoses is reported. This modified armed-disarmed approach is relying on the observation that 2-N-trichloroethoxycarbonyl derivatives of Sbenzoxazolyl glycosides are significantly more reactive than their 2-N-phthaloyl counterparts in MeOTf-promoted glycosylations. This allowed efficient chemoselective synthesis of 1,2-translinked oligosaccharides, the disarmed reducing end of which can be activated for immediate second step glycosidation in the presence of a more powerful activator AgOTf. As a result of this two-step activation, trans-trans-patterned trisaccharides could be assembled in a highly efficient manner. This result differs from the classic armed-disarmed technique, according to which usually cis-transpatterned oligosaccharides are generated. Keywords 2; amino; 2; deoxy sugars; glycosylation; carbohydrates; thioimidates The involvement of complex glycostructures in the pathogenesis of deadly diseases such as AIDS, cancer, pneumonia, meningitis, and hepatitis is now well recognized. This knowledge has been translated into an appreciation of carbohydrates as targets for modern therapeutics. 1,2 Amongst a variety of biologically important carbohydrates are the prokaryotic and eukaryotic glycoconjugates which comprise mainly of residues of the 2-amino-2-deoxy-β-Dglucopyranosyl (D-glucosamino) series. Most representative examples include, but are not limited to chitin, a linear homopolymer of 2-acetamido-D-glucosamine (GlcNAc) that is a component of fungal cell wall and arthropod integuments; 3 heparin, a linear sulfated polysaccharide consisting of alternating GlcNAc and L-iduronic acid units that is a major factor in diverse biological processes including blood coagulation, viral infections, cell growth, inflammation, etc.; 4,5 and the lipid-A region of antigenic lipopolysaccharides, an amphiphilic macromolecule composed of two D-glucosamine residues that has been shown to effect a variety of inflammatory processes. 6,7 Multiple glycosamino residues have been also found in a variety of tumor-associated glycosphingolipids. 8 Although it is now possible to selectively cleave, isolate, purify, and characterize certain classes of natural glycostructures, their accessibility in pure form is still limited. As a result, methods for the synthesis of glycosides and oligosaccharides containing 2-deoxy-2-amino residues have been the focus of a considerable amount of research. 9-11 A vast majority of naturally-occurring glycosamine residues are N-acetylated and linked via 1,2-trans (β-D-gluco/galacto) linkage. However, it has been shown that glycosylation of complex aglycones with glycosyl donors bearing a 2-acetamido-2-deoxy functionality is usually impractical. 9,11 Unlike the reactive acyloxonium intermediate formed via these glycosylations, the yields achieved in these glycosyla...

Direct chemical glycosylation with pentenyl- and thioglycoside donors of N-acetylglucosamine

“…7 GlcNAc thioglycoside donors have been used as precursors to mask the reducing sugar for later glycosyl amine synthesis 16,17 and recently with some success in glycosylation reactions. [18][19][20] GlcNAc-pentenyl glycoside donors have only been used to a very limited extent for the synthesis of oxazoline for enzymatic glycosylation 21 and for the chemical introduction of a 1-azido function 22 and never in combination with metal triflates. To the best of our knowledge there are no reports investigating GlcNAc-pentenyl glycoside donors as reactants in O-glycosylation reactions.…”

Glycosyl thioimidates as versatile building blocks for organic synthesis

“…In attempts to employ the SBox moiety with 2-amino-2-deoxy glycoside donors, it was observed that 2- N -trichloroethoxycarbonyl (Troc) derivatives are significantly more reactive than their 2- N -phthaloyl counterparts in MeOTf-promoted glycosylations [72]. This modified armed-disarmed approach allowed for an efficient chemical synthesis of 1,2- trans -linked oligosaccharides (Scheme 9).…”

Recent trends in the synthesis of O-glycosides of 2-amino-2-deoxysugars

“…Very recently, the anomeric acetyl moiety was converted into chloride 90 and then into S-benzoxazolyl (SBox) glycosyl donor 98 (Scheme 18). 211 The latter derivative showed potent glycosyl donor properties; for example, glycosylation of the glycosyl acceptor 99 in the presence of AgOTf provided 1,2-trans-linked disaccharide 100 in 89% yield.…”

“…211 The Troc group has been found to be stable under a wide range of standard conditions typically used in carbohydrate synthesis. 314 Its sensitivity to alcoholysis under basic conditions permits convenient transformations into other carbamates.…”

“…While the above glycosyl donors have proved to be potent and efficient, other glycosyl donors, such as phenylselenides, 62,427 trifluoroacetimidates, 428,429 and thioimidates, 211 have also been investigated. Deprotection of the phthaloyl group can be achieved with hydrazine hydrate in MeOH or EtOH, 370,371,388,430 alcoholic methylamine, 431,432 ethylenediamine in BuOH or EtOH, 368,376,380,[433][434][435] ammonia in MeOH, 398 sodium borohydride, 401,436 and hydrazine acetate, 437 to form a free amine.…”