The logic of chemical synthesis

Catalytic glycosylation has been a central reaction in carbohydrate chemistry since its introduction by Fischer 125 years ago, but it is only in the past three to four decades that catalytic methods for synthesizing oligosaccharides have appeared. Despite the development of numerous elegant and ingenious catalytic glycosylation methods, only a few are in general use. This review covers all methods of catalytic glycosylation with the focus on the development and application in oligosaccharide synthesis and provide an overview of the scope and limitations of these. The review also includes relevant mechanistic studies of catalytic glycosylations. The future of catalytic glycosylation chemistry is discussed, including specific, upcoming methods and possible directions for the field of research in general.

Catalytic Glycosylations in Oligosaccharide 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

Divergent Cascade Construction of Skeletally Diverse “Privileged” Pyrazole‐Derived Molecular Architectures

Over the last decade, Diversity-Oriented Synthesis (DOS) has become a new paradigm for developing large collections of structurally diverse small molecules as probes to investigate biological pathways, and to provide a larger array of the chemical space. Drug discovery and chemical biology are taking advantage of DOS approaches to exploit highly-diverse and complex molecular platforms, producing advances in both target and ligand discovery. In this view, carbohydrates are attractive building blocks for DOS libraries, due to their stereochemical diversity and high density of polar functional groups, thus offering many possibilities for chemical manipulation and scaffold decoration. This review will discuss research contributions and perspectives on the application of carbohydrate chemistry to explore the accessible chemical space through appendage, stereochemical and scaffold diversity.

Carbohydrates in diversity-oriented synthesis: challenges and opportunities

Novel substrates that combine dicobalt hexacarbonyl propargyl (Nicholas) and pyranose-derived allylic (Ferrier) cations have been generated by treatment of hexacarbonyldicobalt (C-1)-alkynyl glycals with BF3 (.) Et2 O. The study of these cations has resulted in the discovery of novel reaction pathways that have shown to be associated to the nature of O-6 substituent in the starting alkynyl glycals. Accordingly, compounds resulting from ring expansion (oxepanes), ring contraction (tetrahydrofurans), or branched pyranoses, by incorporation of nucleophiles, can be obtained from 6-O-benzyl, 6-hydroxy, or 6-O-silyl derivatives, respectively. The use of a 6-O-allyl alkynyl glycal led to a suitable funtionalized oxepane able to experience an intramolecular Pauson-Khand cyclization leading to a single tricyclic derivative.

A substrate-based approach to skeletal diversity from dicobalt hexacarbonyl (C1)-alkynyl glycals by exploiting its combined Ferrier-Nicholas reactivity.

The transformation of glycals (1,2-unsaturated cyclic carbohydrate derivatives) into 2,3-unsaturated glycosyl derivatives, currently termed Ferrier rearrangement, is a well-established synthetic procedure with ample use in the fields of carbohydrate and organic chemistry. This article highlights the developments in the Ferrier rearrangement published in the literature since the last review, in 2013, to early 2016.

Ferrier rearrangement: an update on recent developments

Unsaturated carbohydrate derivatives are useful intermediates in synthetic transformations leading to a variety of compounds. The aim of this review is to highlight the rich chemistry of ∆-2,3 unsaturated pyranosides, emphasizing the variety of transformations that have been carried out in these substrates during the last decade.

/pdf/a-survey-of-recent-synthetic-applications-of-2-3-dideoxy-hex-2ie5j1d613.pdf

A Survey of Recent Synthetic Applications of 2,3-Dideoxy-Hex-2-enopyranosides

Diversity-Oriented Synthetic Endeavors of Newly Designed Ferrier and Ferrier-Nicholas Systems Derived from 1-C-Alkynyl-2-deoxy-2-C-Methylene Pyranosides

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.

Silvia Miranda

Papers

A substrate-based approach to skeletal diversity from dicobalt hexacarbonyl (C1)-alkynyl glycals by exploiting its combined Ferrier-Nicholas reactivity.

Ferrier rearrangement: an update on recent developments

A Survey of Recent Synthetic Applications of 2,3-Dideoxy-Hex-2-enopyranosides

Diversity-Oriented Synthetic Endeavors of Newly Designed Ferrier and Ferrier-Nicholas Systems Derived from 1-C-Alkynyl-2-deoxy-2-C-Methylene Pyranosides

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