Origins of Temperature-Dependent Anomeric Selectivity in Glycosylations with an L-Idose Thioglycoside.

L-Idose thioglycosides are useful glycosyl donors for the construction of glycosaminoglycan oligosaccharides. When activated with NIS and catalytic TMSOTf in the presence of methanol, the stereoselectivity of O-glycosylation displays an intriguing dependence on the reaction temperature, with an increased preference for formation of the α-glycoside at higher temperatures. Using a combination of vt-NMR spectroscopy and DFT calculations, we show how a simple mechanistic model, based on competing reactions of the iodinated thioglycoside, can explain the main features of the temperature dependence. In this model, the increased selectivity at high temperature is attributed to differences among the entropy and energy terms of the competing reaction pathways. Neighbouring-group participation (giving an intermediate acyloxonium ion) plays an increasingly dominant role as temperature is raised. The general features of this kinetic regime may also apply more broadly to other glycosylations that likewise favour α-glycoside formation at high temperature.

An Improved Protocol for the Stereoselective Synthesis of ß-d-Glycosyl Fluorides from 2-O-Acyl Thioglycosides.

A safe and operationally simple protocol for the preparation of ß-d-glycosyl fluorides is presented. We demonstrate that a precise combination of XtalFluor-M, N-bromosuccinimide, and Et3N·3HF can mediate facile, high-yielding, and diastereoselective conversions of 2-O-acyl thioglycosides to ß-d- and other 1,2-trans glycosyl fluorides. The key roles of these reagents are dissected in this work, as is the impact of their interplay on the fluorination stereoselectivity.

Computational discoveries of reaction mechanisms: recent highlights and emerging challenges.

This review examines some of the notable advances and trends that have shaped the field of computational elucidation of organic reaction mechanisms over the last 10-15 years. It highlights the types of mechanistic problems that have recently become possible to study and summarizes the methodological developments that have permitted these new advances. Case studies are taken from three representative areas of organic chemistry-asymmetric catalysis, glycosylation reactions, and single electron transfer reactions-which illustrate themes common to the broader field. These include the trend towards modelling systems that are increasingly complex (both structurally and mechanistically), the growing appreciation of the mechanistic roles of non-covalent interactions, and the increasing ability to explore dynamical features of reaction mechanisms. Some interesting new challenges that have emerged in the field are identified.

From Cancer to COVID-19: A Perspective on Targeting Heparan Sulfate-Protein Interactions.

Heparan sulfate (HS) is a complex, polyanionic polysaccharide ubiquitously expressed on cell surfaces and in the extracellular matrix. HS interacts with numerous proteins to mediate a vast array of biological and pathological processes. Inhibition of HS-protein interactions is thus an attractive approach for new therapeutic development for cancer and infectious diseases, including COVID-19; however, synthesis of well-defined native HS oligosaccharides remains challenging. This has aroused significant interest in the development of HS mimetics which are more synthetically tractable and have fewer side effects, such as undesired anticoagulant activity. This account provides a perspective on the design and synthesis of different classes of HS mimetics with useful properties, and the development of various assays and molecular modelling tools to progress our understanding of their interactions with HS-binding proteins.

Site-Selective Photobromination of O-Acetylated Carbohydrates in Benzotrifluoride.

Ferrier photobromination enables direct synthetic access to valuable 5-C-bromosugars but has limitations that restrict its broader use. The reaction is typically conducted in CCl4 heated at reflux with irradiation by broad spectrum, energy-inefficient heat lamps. Herein, we demonstrate that the reaction proceeds rapidly and efficiently with PhCF3 as a safe and environmentally benign alternative to CCl4 at mild temperatures (≤40 °C) inside a compact photoreactor fitted with purple light-emitting diodes (LEDs).