Chiral Brønsted Acid Mediated Glycosylation with Recognition of Alcohol Chirality

Abstract

Many carbohydrate-containing natural products, which possess mono-and 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. [1] It is now recognized that carbohydrates are at the heart of a multitude of biological events. [1] Additionally, some glycomolecules have been developed as new functional materials. [2] 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. [3] 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. [4] In this study, complete b stereoselectivity and moderate diastereoselectivity were observed. Furthermore, biocatalytic glycosylation resolution of racemic tetrahydroberberrubine was reported by Yu et al. [5] 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. [6,7] 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 1 a [8] and the binol-derived Brønsted acid 2 (Akiyama-Terada catalyst) [9] as glycosyl donor and chiral Brønsted acids, ...

Recent Developments in Stereoselective Chemical Glycosylation

“…Thus, when ent ‐ 29 was used, the β‐selectivity of the glycosylation dropped significantly under the same reaction conditions. This observation is in line with results from the Bennett and Toshima labs, who reported that stereochemical match and mismatch played a role in chiral phosphoric acid‐catalyzed glycosylations. Later, the Nagorny group applied the chiral phosphoric acid in the regioselective synthesis of aminoglycosides …”

Stereocontrolled 1,2-cis glycosylation as the driving force of progress in synthetic carbohydrate chemistry

“…Very recently, Toshima and co-workers reported a novel approach that makes use of the chiral recognition of aglycones. 89 Thus, in glycosylations of racemic alcohols in the presence of a chiral Brønsted acid activator, one enantiomer was glycosylated preferentially and the glycosides were obtained with high stereoselectivity and yields.…”

A propos of glycosyl cations and the mechanism of chemical glycosylation; the current state of the art

“…A twelve-membered cyclic transition state is invoked in which the phosphoric acid hydrogen simultaneously bonds to the donor and acceptor and preorganizes the latter for an S N 2-type displacement. 89 …”