exo-Glycal Chemistry: General Aspects and Synthetic Applications for Biochemical Use

Abstract

It is well known that carbohydrates play an indispensable role in a variety of essential biological activities, such as cell-cell adhesion, bacteria and virus infections, and tumor metastasis. Among an increasing number of sugars and sugar mimetics that have been designed and synthesized for the purpose of drug discovery, C-glycosides are considered to be one of the best choices on account of their stability and resemblance as they differ from normal glycosides only in glycosidic linkages. exo-Glycals are unsaturated sugars that have a double bond attached to the anomeric center outside the sugar ring. These carbohydrate molecules are useful for the synthesis of C-glycosides and compounds containing quaternary carbons, provided that the olefin can be properly reduced or functionalized. This review places special emphasis on two aspects of exo-glycals including general methods of preparation and synthetic applications for making biologically important molecules. The first half discusses the methods of addition/elimination and Ramburg-Bäcklund rearrangement that offer many beneficial features including a wide range of double bond substitutions, limited reaction steps, easy operation and good overall yields. The rest of the article demonstrates a number of synthetic studies using exo-glycals as the starting materials. The target molecules can be categorized into three groups, namely C-glycosides, enzyme inhibitors and bioactive natural products.

Recent Advances in Transition Metal-Catalyzed Glycosylation

“…127-139 They are of particular interest because of their resistance to metabolic processing, making them viable drug candidates and competitive inhibitors of processing enzymes. 127-132 While catalytic approaches to C -glycosides are somewhat rare, there are numerous methods available for constructing the anomeric carbon-carbon bond, where generation of electrophilic, nucleophilic, or radical character is observed at C(1). However, most of these approaches rely on substrate control to provide selectivity in the reaction.…”

Visible-Light-Mediated, Chemo- and Stereoselective Radical Process for the Synthesis of C-Glycoamino Acids

“…C -Glycosyl amino acids are a unique class of compounds widely present in nature that have an enormously diverse array of biological properties . Notable examples of substances in this family include the peptidyl nucleoside antibiotics amipurimycin, polyoxins, and nikkomycin, which have potent antimycotic activities against various human pathogenic fungi and bacteria (Scheme A). , More pronounced impacts of C -glycosyl amino acids arise from their broad application in biomedical and drug discovery studies of glycopeptides and proteins. , Finally, the presence of C–C linkages to anomeric centers gives members of this family higher metabolic stabilities and lipophilicities than those of O–C bond-containing counterparts. In many instances, this feature leads to improved biological activities, membrane permeabilities, and bioavailabilities. , …”

Highly (Z)-Diastereoselective Synthesis of Trifluoromethylated exo-Glycals via Photoredox and Copper Catalysis

“…exo -Glycals, such as the molecule 1-( Z ) , have been recognized as important structural motifs for the inhibition of enzymes, which include glycosidases and glycosyltransferases . In this context, our group has reported several methods for preparing phosphono- exo -glycals 2-( Z , E ) (Figure ) which could inhibit UDP-glactopyranose mutase (UGM) and galactofuranosyltransferases 1 and 2 (Gl f Ts). − These enzymes are involved in the biosynthesis of the Mycobacterium tuberculosis cell wall, the causative agent of tuberculosis, and are validated targets for the development of antitubercular drugs. − The presence of several fluorine atoms in close proximity within the scaffold of the inhibitor (e.g., CF 3 –CF 2 , CF 3 etc.)…”