Total synthesis of the hexasaccharide arabinan domain of mycobacterial arabinogalactan.

The hexasaccharide arabinan domain of Mycobacterial Arabinogalactan was provided with the versatile methodology toward ß-selective arabinofuranosylation directed by B(C6F5)3, demonstrating the effectiveness of the ß-arabinofuranosylation strategy. Derivatization of the amino moiety at the reducing end are essential prerequisites for elucidating the biosynthetic pathway and conjugating of this compound to a protein carrier for vaccine generation.

B(C6F5)3-Catalyzed Stereoselective 1,2-cis Arabinofuranosylation with a Conformationally Constrained Donor.

Compared with stereoselective glycosylation methods mainly addressed on the preparation of pyranose glycosides, the furanosylation has been more limited, especially for the 1,2-cis arabinofuranosylation. Herein, we report a novel stereoselective 1,2-cis-arabinofuranosylation strategy using a conformationally restricted 3,5-O-xylylene-protected arabinofuranosyl donor on activation with B(C6F5)3 for desired targets in moderate to excellent yields and ß-stereoselectivity. The effectiveness of the 1,2-cis-arabinofuranosylation strategy was demonstrated successfully with various acceptors, including carbohydrate alcohols.

ZnI2-Mediated ß-Galactosylation of C2-Ether-Type Donor.

Conventional glycosylation with galactosyl donors having C-2 benzyl (Bn) ether-type functionality often leads to anomeric mixtures, due to the anomeric and steric effects that stabilize the 1,2-cis-α- and 1,2-trans-ß-glycosides, respectively. Herein we report a versatile ZnI2-directed ß-galactosylation approach employing a 4,6-O-tethered and 2-O-Bn galactosyl donor for the stereoselective and efficient synthesis of ß-O-galactosides. With a broad substrate scope, the reaction tolerates a wide range of functional groups and complex molecular architectures, providing stereocontrolled ß-galactosides in moderate to excellent yields. The practicality of this transformation is demonstrated through the synthesis of a tetrasaccharide arabinogalactan fragment with high stereoselectivity.

Recent advances in stereoselective 1,2-cis-O-glycosylations.

For the stereoselective assembly of bioactive glycans with various functions, 1,2-cis-O-glycosylation is one of the most essential issues in synthetic carbohydrate chemistry. The cis-configured O-glycosidic linkages to the substituents at two positions of the non-reducing side residue of the glycosides such as α-glucopyranoside, α-galactopyranoside, ß-mannopyranoside, ß-arabinofuranoside, and other rather rare glycosides are found in natural glycans, including glycoconjugate (glycoproteins, glycolipids, proteoglycans, and microbial polysaccharides) and glycoside natural products. The way to 1,2-trans isomers is well sophisticated by using the effect of neighboring group participation from the most effective and kinetically favored C-2 substituent such as an acyl group, although high stereoselective synthesis of 1,2-cis glycosides without formation of 1,2-trans isomers is far less straightforward. Although the key factors that control the stereoselectivity of glycosylation are largely understood since chemical glycosylation was considered to be one of the useful methods to obtain glycosidic linkages as the alternative way of isolation from natural sources, strictly controlled formation of these 1,2-cis glycosides is generally difficult. This minireview introduces some of the recent advances in the development of 1,2-cis selective glycosylations, including the quite recent developments in glycosyl donor modification, reaction conditions, and methods for activation of intermolecular glycosylation, including the bimodal glycosylation strategy for 1,2-cis and 1,2-trans glycosides, as well as intramolecular glycosylations, including recent applications of NAP-ether-mediated intramolecular aglycon delivery.

Recent Chemical and Chemoenzymatic Strategies to Complex-Type N-Glycans.

Glycosylation is one of the major forms of protein post-translational modification. N-glycans attached to proteins by covalent bonds play an indispensable role in intercellular interaction and immune function. In human bodies, most of the cell surface glycoproteins and secreted glycopeptides are modified with complex-type N-glycans. Thus, for analytical or medicinal purposes, efficient and universal methods to provide homogeneous complex-type N-glycans have been an urgent need. Despite the extremely complicated structures, tremendous progress in the synthesis of N-glycans has been achieved. On one hand, chemical strategies are shown to be effective to prepare core oligosaccharides of N-glycans by focusing on stereoselective glycosylations such as ß-mannosylation and α-sialylation, as well as the methodology of the N-glycan assembly. On the other hand, chemoenzymatic strategies have also become increasingly powerful in recent years. This review attempts to highlight the very recent advancements in chemical and chemoenzymatic strategies for eukaryotic complex-type N-glycans.

Zinc(II) Iodide-Directed ß-Mannosylation: Reaction Selectivity, Mode, and Application.

A direct, efficient, and versatile glycosylation methodology promises the systematic synthesis of oligosaccharides and glycoconjugates in a streamlined fashion like the synthesis of medium to long-chain nucleotides and peptides. The development of a generally applicable approach for the construction of 1,2-cis-glycosidic bond with controlled stereoselectivity remains a major challenge, especially for the synthesis of ß-mannosides. Here, we report a direct mannosylation strategy mediated by ZnI2, a mild Lewis acid, for the highly stereoselective construction of 1,2-cis-ß linkages employing easily accessible 4,6-O-tethered mannosyl trichloroacetimidate donors. The versatility and effectiveness of this strategy were demonstrated with successful ß-mannosylation of a wide variety of alcohol acceptors, including complex natural products, amino acids, and glycosides. Through iteratively performing ZnI2-mediated mannosylation with the chitobiosyl azide acceptor followed by site-selective deprotection of the mannosylation product, the novel methodology enables the modular synthesis of the key intermediate trisaccharide with Man-ß-(1 → 4)-GlcNAc-ß-(1 → 4)-GlcNAc linkage for N-glycan synthesis. Theoretical investigations with density functional theory calculations delved into the mechanistic details of this ß-selective mannosylation and elucidated two zinc cations' essential roles as the activating agent of the donor and the principal mediator of the cis-directing intermolecular interaction.

ZnI2-Directed Stereocontrolled α-Glucosylation.

Here we report a glucosylation strategy mediated by ZnI2, a cheap and mild Lewis acid, for the highly stereoselective construction of 1,2-cis-O-glycosidic linkages using easily accessible and common 4,6-O-tethered glucosyl donors. The versatility and effectiveness of the α-glucosylation strategy were demonstrated successfully with various acceptors, including complex alcohols. This approach demonstrates the feasibility of the modular synthesis of various α-glucans with both linear and branched backbone structures.