Deoxy-sugars often play a critical role in modulating the potency of many bioactive natural products. Accordingly, there has been sustained interest in methods for their synthesis over the past several decades. The focus of much of this work has been on developing new glycosylation reactions that permit the mild and selective construction of deoxyglycosides. This Review covers classical approaches to deoxyglycoside synthesis, as well as more recently developed chemistry that aims to control the selectivity of the reaction through rational design of the promoter. Where relevant, the application of this chemistry to natural product synthesis will also be described.

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Methods for 2-Deoxyglycoside Synthesis.

The logic of chemical synthesis

This Review summarizes close to 500 primary publications and surveys published since 2000 about the syntheses and diverse bioactivities of C-glycopyranosyl (het)arenes. A classification of the preparative routes to these synthetic targets according to methodologies and compound categories is provided. Several of these compounds, regardless of their natural or synthetic origin, display antidiabetic properties due to enzyme inhibition (glycogen phosphorylase, protein tyrosine phosphatase 1B) or by inhibiting renal sodium-dependent glucose cotransporter 2 (SGLT2). The latter class of synthetic inhibitors, very recently approved as antihyperglycemic drugs, opens new perspectives in the pharmacological treatment of type 2 diabetes. Various compounds with the C-glycopyranosyl (het)arene motif were subjected to biological studies displaying among others antioxidant, antiviral, antibiotic, antiadhesive, cytotoxic, and glycoenzyme inhibitory effects.

C-Glycopyranosyl Arenes and Hetarenes: Synthetic Methods and Bioactivity Focused on Antidiabetic Potential

Chemical C-glycosylation has been well developed to improve stereoselectivity in recent years. Due to its high efficiency to build C-glycosides or O-cyclic compounds, C-glycosylation has found widespread use in the synthesis of biologically active molecules. This review highlights the C-glycosylation methods that have been practised in the total synthesis of natural products and pharmaceuticals in the past decade.

Recent progress of C-glycosylation methods in the total synthesis of natural products and pharmaceuticals

Recent developments in β-C-glycosides: synthesis and applications

Formation and reactivity of new Nicholas–Ferrier pyranosidic cations: novel access to oxepanes via a 1,6-hydride shift/cyclization sequence

The presence of an unsaturation in a pyranose derivative provides a powerful handle for the creation of new compounds displaying a variety of molecular skeletons. This contribution focuses on investigations related to the use of pyranose glycals in the creation of skeletally-diverse derivatives that have appeared in the literature during the last eight years.

Pyranose glycals in the generation of skeletal diversity

Abstract Pyranosidic allylic (Ferrier) cations that share dicobalt hexacarbonyl propargyl (Nicholas) stabilization at C-1, can be easily generated by treatment of hexacarbonyldicobalt alkynyl glycals with BF3·OEt2, and display a remarkable reactivity leading to a variety of products. The substituent at O-6 in these glycals plays a pivotal role in directing the outcome of the transformations. Accordingly, 6-O-benzyl or 6-O-allyl groups cause a series of transformations resulting in the stereoselective formation of oxepanes through a process that involves an initial hydride transfer step from the allyl or benzyl substituent to the Ferrier–Nicholas cation. On the contrary, 6-OH derivatives undergo an overall ring contraction to branched tetrahydrofuran derivatives. 6-O-Silyl derivatives, in the presence of heteroaryl nucleophiles, were transformed into C-3 branched bis-C-C-glycosides, containing two of such molecules.

Fernando Lobo

Papers

Formation and reactivity of new Nicholas–Ferrier pyranosidic cations: novel access to oxepanes via a 1,6-hydride shift/cyclization sequence

Pyranose glycals in the generation of skeletal diversity

Ferrier-Nicholas pyranosidic cations: application to diversity-oriented synthesis

Sugar furanoses as useful handles for molecular diversity

Ferrier–Nicholas Cations from C-3-Alkynylglycals: Access to C-3-Branched Allylic Glycosides and Ring-Opening Derivatives