Sulfoglycolipids and Related Analogues of Mycobacterium tuberculosis: Chemical Synthesis and Immunological Studies.

Mycobacterium tuberculosis (Mtb) causes tuberculosis as one major threat to human health, which has been deteriorated owing to the emerging multidrug resistance. Mtb contains a complex lipophilic cell wall structure that is important for bacterial persistence. Among the lipid components, sulfoglycolipids (SGLs), known to induce immune cell responses, are composed of a trehalose core attached with a conserved sulfate group and 1-4 fatty acyl chains in an asymmetric pattern.

Orthogonal Glycosylation with Phosphate Acceptors for Expeditious Synthesis of Bacterial Inner Core Oligosaccharides.

We report a practical one-pot glycosylation strategy for synthesis of bacterial inner core oligosaccharides that composed of unavailable L-glycero-D-manno and D-glycero-D-manno-heptopyranose components. The glycosylation method features a new orthogonal glycosylation procedure; whereby a phosphate acceptor is coupled with a thioglycosyl donor producing a disaccharide phosphate, which can be engaged in another orthogonal glycosylation procedure to couple with a thioglycosyl acceptor. The phosphate acceptors used in above one-pot procedure are directly prepared from thioglycosyl acceptors via the in-situ phosphorylation.

Tunable Strategy for the Asymmetric Synthesis of Sulfoglycolipids from Mycobacterium tuberculosis To Elucidate the Structure and Immunomodulatory Property Relationships.

We developed a versatile asymmetric strategy to synthesize different classes of sulfoglycolipids (SGLs) from Mycobacterium tuberculosis. The strategy features the use of asymmetrically protected trehaloses, which were acquired from the glycosylation of TMS α-glucosyl acceptors with benzylidene-protected thioglucosyl donors. The positions of the protecting groups at the donors and acceptors can be fine-tuned to obtain different protecting-group patterns, which is crucial for regioselective acylation and sulfation.

Metabolic Isolation, Stereochemical Determination, and Total Synthesis of Predominant Native Cholesteryl Phosphatidyl-α-glucoside from Carcinogenic .

We report the isolation and stereochemical determination of the predominant native cholesteryl 6--phosphatidyl α-glucoside (CPG) from via an integrated biological and chemical strategy. The strategy employed (i) the metabolic isolation of a CPG analogue and (ii) the enzymatic degradation of the analogue to obtain the native lactobacillic acid for the stereochemical determination. The absolute stereochemistry of the acid was found to be 11 and 12.

Enhanced enzymatic production of cholesteryl 6'-acylglucoside impairs lysosomal degradation for the intracellular survival of Helicobacter pylori.

Background: During autophagy defense against invading microbes, certain lipid types are indispensable for generating specialized membrane-bound organelles. The lipid composition of autophagosomes remains obscure, as does the issue of how specific lipids and lipid-associated enzymes participate in autophagosome formation and maturation. Helicobacter pylori is auxotrophic for cholesterol and converts cholesterol to cholesteryl glucoside derivatives, including cholesteryl 6'-O-acyl-α-D-glucoside (CAG).

Cascade In Situ Phosphorylation and One-Pot Glycosylation for Rapid Synthesis of Heptose-Containing Oligosaccharides.

We report a one-pot glycosylation strategy for achieving rapid syntheses of heptose (Hep)-containing oligosaccharides. The reported procedure was designed to incorporate an in situ phosphorylation step into an orthogonal one-pot glycosylation. Hep-containing oligosaccharides were assembled directly from building blocks with minimal effort expended on manipulation of protecting and aglycone leaving groups.

Sub-stoichiometric reductive etherification of carbohydrate substrates and one-pot protecting group manipulation.

In this study, we report a new reductive etherification procedure for protection of carbohydrate substrates and its application for one-pot preparation of glycosyl building blocks. The reported procedure features the use of polymethylhydrosiloxane (PMHS) as a sub-stoichiometric reducing agent, which prevents the transilylation side reaction and improves the efficiency of the reductive etherification method. Application of the PMHS reductive etherification procedure for one-pot protecting group manipulation are described.

Cholesteryl α-D-glucoside 6-acyltransferase enhances the adhesion of Helicobacter pylori to gastric epithelium.

Helicobacter pylori, the most common etiologic agent of gastric diseases including gastric cancer, is auxotrophic for cholesterol and has to hijack it from gastric epithelia. Upon uptake, the bacteria convert cholesterol to cholesteryl 6'-O-acyl-α-D-glucopyranoside (CAG) to promote lipid raft clustering in the host cell membranes. However, how CAG appears in the host to exert the pathogenesis still remains ambiguous.

Diverse Synthesis of Natural Trehalosamines and Synthetic 1,1'-Disaccharide Aminoglycosides.

A general strategy for the diverse synthesis of ten disaccharide aminoglycosides, including natural 2-trehalosamine (1), 3-trehalosamine (2), 4-trehalosamine (3), and neotrehalosyl 3,3'-diamine (8) and synthetic aminoglycosides 4-7, 9, and 10, has been developed. The aminoglycoside compounds feature different anomeric configurations and numbers of amino groups. The key step for the synthesis was the glycosylation coupling of a stereodirecting donor with a configuration-stable TMS glycoside acceptor.

A general strategy for diverse syntheses of anhydrolandomycinone, tetrangulol, and landomycinone.

A general synthetic strategy based on a protecting group-promoted CH arylation method was developed for total syntheses of anhydrolandomycinone (1), tetrangulol (2), and landomycinone (3) from the same set of starting materials.

A flexible 1,2-cis α-glycosylation strategy based on in situ adduct transformation.

A flexible 1,2-cis α-selective glycosylation strategy for a wide range of glycosyl donors and acceptors has been developed, which is based on an in situ adduct transformation protocol. Based on this strategy, both NFM-derived and iodide covalent adducts can be accessed for glycosylation. Using low temperature NMR spectroscopy, the aforementioned glycosyl adducts were detected.

Selective Detection of Shiga-like Toxin 1 from Complex Samples Using Pigeon Ovalbumin Functionalized Gold Nanoparticles as Affinity Probes.

Escherichia coli O157:H7 is a foodborne pathogen. This bacterial strain can generate Shiga-like toxins (SLTs), which can cause serious sickness and even death. Thus, it is important to develop effective and sensitive methods that can be used to rapidly identify the presence of SLTs from complex samples.

Unusually Stable Picoloyl-Protected Trimethylsilyl Glycosides for Nonsymmetrical 1,1'-Glycosylation and Synthesis of 1,1'-Disaccharides with Diverse Configurations.

Nonsymmetrical 1,1'-disaccharides and related derivatives constitute structural components in various glycolipids and natural products. Some of these compounds have been shown to exhibit appealing biological properties. We report a direct yet stereoselective 1,1'-glycosylation strategy for the synthesis of nonsymmetrical 1,1'-disaccharides with diverse configurations and sugar components.

Development of a novel engineered antibody targeting Neisseria species.

Objectives: A Neissaria bacterial pilus sugar, bacillosamine, was synthesized and, for the first time, used as a probe to screen a single-chain variable fragment (scFv).

Results: Four Neisseria, Neisseria gonorrhoeae, Neisseria meningitidis, Neisseria sicca and Neisseria subflava, and two negative controls, Streptococcus pneumoniae and Escherichia coli, were tested through ELISA, immunostaining and gold nanoparticle immunological assay. All results indicated that the selected scFv is feasible for the specific detection of Neisseria species via the recognition of bacillosamine.

Metabolic labelling of cholesteryl glucosides in reveals how the uptake of human lipids enhances bacterial virulence.

infects approximately half of the human population and is the main cause of various gastric diseases. This pathogen is auxotrophic for cholesterol, which it converts upon uptake to various cholesteryl α-glucoside derivatives, including cholesteryl 6'-acyl and 6'-phosphatidyl α-glucosides (CAGs and CPGs). Owing to a lack of sensitive analytical methods, it is not known if CAGs and CPGs play distinct physiological roles or how the acyl chain component affects function.

A concise synthesis of single components of partially sulfated oligomannans.

A concise synthesis of single components of C2 sulfated oligomannans including trimers, tetramers, and pentamers is reported. The synthesis features the application of the DMF-modulation method for the participatory thiomannoside donors in 1,2-transα-glycosidic bond formation. The obtained oligomannans were fully characterized using (1)H, (13)C, COSY, and HSQC NMR spectroscopy.

Magnetic Nanoparticle-Based Platform for Characterization of Shiga-like Toxin 1 from Complex Samples.

Foodborne illness outbreaks resulting from contamination of Escherichia coli O157:H7 remain a serious concern in food safety. E. coli O157:H7 can cause bloody diarrhea, hemolytic uremic syndrome, or even death.

C6 picoloyl protection: a remote stereodirecting group for 2-deoxy-β-glycoside formation.

We reported a remote control glycosylation method using the picoloyl protecting group for 2-deoxy-β-glycosidic bond formation. The method is applicable to various 2-deoxythioglycosyl donors and the utility is illustrated by the synthesis of a deoxytrisaccharide component of landomycins.

Synthesis of oligomeric mannosides and their structure-binding relationship with concanavalin A.

Small glycodendrimers with α-mannosyl ligands were synthesized by using copper-catalyzed azide-alkyne coupling chemistry and some of these molecules were used as multivalent ligands to study the induction of concanavalin A (Con A) precipitation. The results showed that the monovalent mannose ligand could induce the precipitation of Con A. This unexpected finding initiated a series of studies to characterize the molecular basis of the ligand-lectin interaction.

A general synthetic strategy and the anti-proliferation properties on prostate cancer cell lines for natural phenylethanoid glycosides.

A general strategy for the synthesis of phenylethanoid glycosides (PhG) including echinacoside 1, acteoside 2, calceolarioside-A 3 and calceolarioside-B 4 is reported. The strategy features the application of low substrate concentration glycosylation and N-formyl morpholine modulated glycosylation methods for the construction of 1,2-trans β- and α-glycosidic bonds. The reported strategy does not invoke the use of the participatory acyl protecting function, which is incompatible with the ester function present in target PhG compounds.

Preparation of a protected 3-deoxy-D-manno-oct-2-ulosonate glycal donor for the synthesis of β-KDO-containing oligosaccharides.

A practical method for the synthesis of KDO glycal donors was developed. The prepared KDO donors exhibited excellent disastereoselectivity of glycosylation in a CH2Cl2-CH3CN solvent mixture, which was found to be associated with the isopropylidene protection at the C-4 and C-5 hydroxyls. The synthetic use of the KDO donor was demonstrated in the preparation of β-KDO-containing oligosaccharides.

Modulating glycosylation with exogenous nucleophiles: an overview.

The major challenge in carbohydrate synthesis is stereochemical control of glycosidic bond formation. Different glycosylation methods have been developed that are based on the modulation effect of external nucleophiles. This review highlights the development, synthetic application, challenges and outlook of the modulated glycosylation methods.

Tuning reactivity of glycosyl imidinium intermediate for 2-azido-2-deoxyglycosyl donors in α-glycosidic bond formation.

The chemical properties of nucleophile additives were investigated in a modulated glycosylation context. N-Formylmorpholine (NFM) was found to be an effective modulator for glycosylation with less reactive 2-azido-2-deoxythioglucosyl and thiogalactosyl donors.