Many carbohydrate-containing natural products, which possess monoand oligosaccharides, such as proteoglycans, glycoproteins, glycolipids, and antibiotics, are found in nature as important biological substances. A large number of recent biological studies on these glycomolecules at the molecular level have shed light on the biological significance of their carbohydrate units (glycons) in molecular recognition for the transmission of biological information. It is now recognized that carbohydrates are at the heart of a multitude of biological events. Additionally, some glycomolecules have been developed as new functional materials. For example, certain alkyl glycosides are expected to be biodegradable surfactants. Therefore, glycomolecules continue to be the central focus of much research in chemistry, biology, and material science. With this stimulating background, the efficient synthesis of not only the carbohydrate itself, but also carbohydrate-containing products, is of particular interest both in academia and in industry. In this context, glycosylation, which is a crucial organic synthetic method to attach a sugar to other sugar moieties or other molecules (aglycons), is becoming more and more important in synthetic organic chemistry and carbohydrate chemistry, and considerable attention has been directed towards the efficiency of the glycosylation method. From a synthetic standpoint, the efficiency of the glycosylation reaction generally is evaluated by a high chemical yield, regioselectivity, and a/b-stereoselectivity. Unfortunately, little attention has been focused on the important issue of diastereoselectivity of the reaction between the aglycon and glycon units in glycosylation. Herein we report a novel chemical glycosylation method that alters the chiral recognition ability of the aglycon. To the best of our knowledge, this is the first demonstrated example of a chemical glycosylation with recognition of alcohol chirality. Previously, we demonstrated an enzymatic glycosylation of o-nitrophenyl b-d-galactoside and racemic secondary alcohols using b galactosidase from E. coli. In this study, complete b stereoselectivity and moderate diastereoselectivity were observed. Furthermore, biocatalytic glycosylation resolution of racemic tetrahydroberberrubine was reported by Yu et al. While our continuing efforts regarding this issue were unsuccessful, Fairbanks et al. recently reported a/bstereoselective glycosylation of a galactosyl trichloroacetimidate and chiral alcohols using a chiral Brønsted acid. 7] In that study, high b stereoselectivity, induced by a chiral Brønsted acid, was demonstrated. In this context, we expected that use of a chiral Brønsted acid in glycosylation would realize a/b stereoselective and diastereoselective chemical glycosylation by tuning the reaction conditions. To investigate our hypothesis, we selected the glucosyl trichloroacetimidate 1a and the binol-derived Brønsted acid 2 (Akiyama–Terada catalyst) as glycosyl donor and chiral Brønsted acids, respectively (Figure 1). In this case,

Chiral Brønsted Acid Mediated Glycosylation with Recognition of Alcohol Chirality

The total synthesis of amphotericin B

Thermodynamically Controlled Regioselective Glycosylation of Fully Unprotected Sugars through Bis(boronate) Intermediates

Silicon-based materials, namely zeolites, clays, and silica gel have been widely used in organic synthesis, allowing mild reaction conditions and environmentally friendly methodologies. These heterogeneous catalysts are easy to handle, possess nontoxic and noncorrosive character and offer the possibility of recovery and reuse, thus contributing to clean and sustainable organic transformations. Moreover, they present shape-selective properties and provide stereo- and regiocontrol in chemical reactions. Herein, we survey the most significant applications of silicon-based materials as catalysts in carbohydrate chemistry, to mediate important transformations such as glycosylation, sugar protection and deprotection, and hydrolysis and dehydration. Emphasis is placed on their promising synthetic potential in comparison with conventional catalysts.

Zeolites and other silicon-based promoters in carbohydrate chemistry.

A synthetic mannoside derivative, namely, 6-morphinyl-alpha-D-mannopyranoside, shows a naloxone-reversible antinociception that is 100-fold more potent and twice as long lasting compared to morphine when administered intraperitoneally to rats in paw pressure and tail flick tests. The compound does not produce tolerance and binds to rat mu opioid receptors with twice the affinity of morphine. NMR studies suggest that differences of activity between the derivative and its parent compound M6G might be related to their differing molecular dynamic behavior.

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Synthesis, conformation, and biological characterization of a sugar derivative of morphine that is a potent, long-lasting, and nontolerant antinociceptive.

K. Sasaki

Papers

1.07 – O-Glycosidation Methods