ZnI-Mediated -Glycosylations of Various Constrained Glycosyl Donors: Recent Advances in -Selective Glycosylations.

An efficient and versatile glycosylation methodology is crucial for the systematic synthesis of oligosaccharides and glycoconjugates. A direct intermolecular and an indirect intramolecular methodology have been developed, and the former can be applied to the synthesis of medium-to-long-chain glycans like that of nucleotides and peptides. The development of a generally applicable approach for the stereoselective construction of glycosidic bonds remains a major challenge, especially for the synthesis of 1,2- glycosides such as β-mannosides, β-L-rhamnosides, and β-D-arabinofuranosides with equatorial glycosidic bonds as well as α-D-glucosides with axial ones.

Structural elucidation of a capsular polysaccharide from Bacteroides uniformis and its ameliorative impact on DSS-induced colitis in mice.

Capsular polysaccharides derived from Bacteroides species have emerged as potential mitigators of intestinal inflammation in murine models. However, research on capsular polysaccharides from B. uniformis, a Bacteroides species with reduced abundance in colons of patients with ulcerative colitis, remains scarce.

Zinc(ii)-mediated stereoselective construction of 1,2- 2-azido-2-deoxy glycosidic linkage: assembly of K48 capsular pentasaccharide derivative.

The capsular polysaccharide (CPS) is a major virulence factor of the pathogenic and a promising target for vaccine development. However, the synthesis of the 1,2--2-amino-2-deoxyglycoside core of CPS remains challenging to date. Here we develop a highly α-selective ZnI-mediated 1,2- 2-azido-2-deoxy chemical glycosylation strategy using 2-azido-2-deoxy glucosyl donors equipped with various 4,6--tethered groups.

Total synthesis of the hexasaccharide arabinan domain of mycobacterial arabinogalactan.

The hexasaccharide arabinan domain of Mycobacterial Arabinogalactan was provided with the versatile methodology toward β-selective arabinofuranosylation directed by B(CF), demonstrating the effectiveness of the β-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(CF)-Catalyzed Stereoselective 1,2- 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- arabinofuranosylation. Herein, we report a novel stereoselective 1,2--arabinofuranosylation strategy using a conformationally restricted 3,5--xylylene-protected arabinofuranosyl donor on activation with B(CF) for desired targets in moderate to excellent yields and β-stereoselectivity. The effectiveness of the 1,2--arabinofuranosylation strategy was demonstrated successfully with various acceptors, including carbohydrate alcohols.

Synthetic self-adjuvanted multivalent Mucin 1 (MUC1) glycopeptide vaccines with improved in vivo antitumor efficacy.

The tumor-associated glycoprotein Mucin 1 (MUC1) is aberrantly glycosylated on cancer cells and is considered a promising target for antitumor vaccines. The weak immunogenicity and low sequence homology of mouse mucins and human MUC1 are the main obstacles for the development of vaccines. Herein, a self-adjuvanted strategy combining toll-like receptor  2 lipopeptide ligands and T-cell epitopes and the multivalent effect were used to amplify the immune response and evade the unpredictable immunogenicity, generating two self-adjuvanted three-component MUC1 vaccines (mono- and trivalent MUC1 vaccines).

Recent Progress in 1,2- glycosylation for Glucan Synthesis.

Controlling the stereoselectivity of 1,2- glycosylation is one of the most challenging tasks in the chemical synthesis of glycans. There are various 1,2- glycosides in nature, such as α-glucoside and β-mannoside in glycoproteins, glycolipids, proteoglycans, microbial polysaccharides, and bioactive natural products. In the structure of polysaccharides such as α-glucan, 1,2- α-glucosides were found to be the major linkage between the glucopyranosides.

Immunomodulatory Effect and Biological Significance of β-Glucans.

β-glucan, one of the homopolysaccharides composed of D-glucose, exists widely in cereals and microorganisms and possesses various biological activities, including anti-inflammatory, antioxidant, and anti-tumor properties. More recently, there has been mounting proof that β-glucan functions as a physiologically active "biological response modulator (BRM)", promoting dendritic cell maturation, cytokine secretion, and regulating adaptive immune responses-all of which are directly connected with β-glucan-regulated glucan receptors. This review focuses on the sources, structures, immune regulation, and receptor recognition mechanisms of β-glucan.

Molecularly Stimuli-Responsive Self-Assembled Peptide Nanoparticles for Targeted Imaging and Therapy.

Self-assembly has emerged as an extensively used method for constructing biomaterials with sizes ranging from nanometers to micrometers. Peptides have been extensively investigated for self-assembly. They are widely applied owing to their desirable biocompatibility, biodegradability, and tunable architecture.

Strategies for Synthesizing and Enhancing the Immune Response of Cancer Vaccines Based on MUC1 Glycopeptide Antigens.

Cancer vaccines are based on a vaccinology strategy whereby the patient's immune system is harnessed to induce a specific immune response to kill cancer cells and comprises two categories: prophylactic and therapeutic. Glycoprotein mucin 1 (MUC1), which is overexpressed and poorly glycosylated on cancer cells, is one of the most promising candidates for the development of new cancer vaccines. However, it should be noted that mucin-like glycopeptides are poorly immunogenic and unable to elicit effective and long-lasting immune responses.

ZnI-Mediated β-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--α- and 1,2--β-glycosides, respectively. Herein we report a versatile ZnI-directed β-galactosylation approach employing a 4,6--tethered and 2--Bn galactosyl donor for the stereoselective and efficient synthesis of β--galactosides. With a broad substrate scope, the reaction tolerates a wide range of functional groups and complex molecular architectures, providing stereocontrolled β-galactosides in moderate to excellent yields.

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

For the stereoselective assembly of bioactive glycans with various functions, 1,2---glycosylation is one of the most essential issues in synthetic carbohydrate chemistry. The -configured -glycosidic linkages to the substituents at two positions of the non-reducing side residue of the glycosides such as α-glucopyranoside, α-galactopyranoside, β-mannopyranoside, β-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- 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- glycosides without formation of 1,2- isomers is far less straightforward.

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

Glycosylation is one of the major forms of protein post-translational modification. -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 -glycans.

Zinc(II) Iodide-Directed β-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--glycosidic bond with controlled stereoselectivity remains a major challenge, especially for the synthesis of β-mannosides. Here, we report a direct mannosylation strategy mediated by ZnI, a mild Lewis acid, for the highly stereoselective construction of 1,2--β linkages employing easily accessible 4,6--tethered mannosyl trichloroacetimidate donors.

Built-in adjuvants for use in vaccines.

Vaccine refers to biological products that are produced using various pathogenic microorganisms for inoculation. The goal of vaccination is to induce a robust immune response against a specific antigen, thus preventing the organism from getting infected. In vaccines, adjuvants have been widely employed to enhance immunity against specific antigens.

ZnI-Directed Stereocontrolled α-Glucosylation.

Here we report a glucosylation strategy mediated by ZnI, a cheap and mild Lewis acid, for the highly stereoselective construction of 1,2---glycosidic linkages using easily accessible and common 4,6--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.

Systematic synthesis of novel phosphoglycolipid analogues as potential agonists of GPR55.

Rhodopsin-like G protein-coupled receptor (GPCR) GPR55 is attracting attention as a pharmaceutical target, because of its relationship with various physiological and pathological events. Although GPR55 was initially deorphanized as a cannabinoid receptor, lysophosphatidylinositol (LPI) is now widely perceived to be an endogenous ligand of GPR55. Recently, lysophosphatidyl-β-d-glucoside (LPGlc) has been found to act on GPR55 to repel dorsal root ganglion (DRG) neurons.

Lysolipid Chain Length Switches Agonistic to Antagonistic G Protein-Coupled Receptor Modulation.

Activation of lysolipid-sensitive G protein-coupled receptors (GPCR) depends not only on lysolipid class but also on the length and degree of saturation of their respective hydrophobic tails. Positive regulation of these signaling networks caused by the lipid chain length specificity of upstream phospholipases is firmly established. Nonagonistic lysolipid homologues, featuring incompatible lipid tails, have been suggested to indirectly modulate GPCR signaling by delaying agonist catabolism.

Unified Strategy toward Stereocontrolled Assembly of Various Glucans Based on Bimodal Glycosyl Donors.

Polymers of glucose, the most abundant and one of the biologically important natural products, named glucans are widely present in fungi, bacteria, mammals, and plants with various anomeric configurations and glycosidic linkages. Because of their structural diversity, the unified strategy for the assembly of pure glucans is yet to be developed. Herein, we describe a general strategy that is applicable to construction of all types of glucans by exploiting a bimodal glycosyl donor equipped with C2--TsNHbenzyl ether (TAB), which enables stereocontrolled synthesis of both α- and β-glycosides by switching reaction conditions.

Stereodivergent Mannosylation Using 2- O-( ortho-Tosylamido)benzyl Group.

We report a novel strategy for obtaining both anomers from a single mannosyl donor equipped with a C2- o-TsNHbenzyl ether (2- O-TAB) by switching reaction conditions. In particular, the formation of various β-mannosides was achieved with high selectivity by using a mannosyl phosphite in the presence of ZnI.

Squaryl group modified phosphoglycolipid analogs as potential modulators of GPR55.

Lysophosphatidyl glucoside (LPGlc) is a structurally unique glycolipid that acts as a guidance cue for extending axons during central nervous system development by activating the class A G protein coupled receptor (GPR) 55 of spinal cord sensory axons. GPR55 not only plays an important role during development, but is also implicated in many disease states, rendering molecules that target GPR55 of widespread interest. In this study, we developed synthetic access to a novel class of LPGlc analogues featuring a squaryl diamide group as surrogate for the phosphodiester.

Bimodal Glycosyl Donors Protected by 2- O-( ortho-Tosylamido)benzyl Group.

A glucosyl donor equipped with C2- o-TsNHbenzyl ether was shown to provide both α- and β-glycosides stereoselectivity, by changing the reaction conditions. Namely, β-glycosides were selectively obtained when the trichloroacetimidate was activated by TfNH. On the other hand, activation by TfOH in EtO provided α-glycosides as major products.

Nanoparticles of Short Cationic Peptidopolysaccharide Self-Assembled by Hydrogen Bonding with Antibacterial Effect against Multidrug-Resistant Bacteria.

Cationic antimicrobial peptides (AMPs) and polymers are active against many multidrug-resistant (MDR) bacteria, but only a limited number of these compounds are in clinical use due to their unselective toxicity. The typical strategy for achieving selective antibacterial efficacy with low mammalian cell toxicity is through balancing the ratio of cationicity to hydrophobicity. Herein, we report a cationic nanoparticle self-assembled from chitosan-graft-oligolysine (CSM5-K5) chains with ultralow molecular weight (1450 Da) that selectively kills bacteria.

A concise route to the highly-functionalized azetidine precursor: the enantioselective synthesis of penaresidin B.

An efficient and high-yielding synthesis of penaresidin B is disclosed herein. The concise 8-step synthesis of azetidine aldehyde was devised by incorporating our novel strategy for ready access to 3-amino-2,3-dideoxysugars via regio- and stereoselective tandem hydroamination/glycosylation of glycal as the key step.

Insights into the programmed ketoreduction of partially reducing polyketide synthases: stereo- and substrate-specificity of the ketoreductase domain.

One of the hallmarks of iterative polyketide synthases (PKSs) is the programming mechanism which is essential for the generation of structurally diverse polyketide products. In partially reducing iterative PKSs (PR-PKSs), the programming mechanism is mainly dictated by the ketoreductase (KR) domain. The KR domain contributes to the programming of PR-PKSs through selective reduction of polyketide intermediates.