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The stereoselectivity and yield in glycosylation reactions are paramount but unpredictable. We have developed a database of acceptor nucleophilic constants (Aka) to quantify the nucleophilicity of hydroxyl groups in glycosylation influenced by the steric, electronic and structural effects, providing a connection between experiments and computer algorithms. The subtle reactivity differences among the hydroxyl groups on various carbohydrate molecules can be defined by Aka, which is easily accessible by a simple and convenient automation system to assure high reproducibility and accuracy. A diverse range of glycosylation donors and acceptors with well‐defined reactivity and promoters were organized and processed by the designed software program "GlycoComputer" for prediction of glycosylation reactions without involving sophisticated computational processing. The importance of Aka was further verified by random forest algorithm, and the applicability was tested by the synthesis of a Lewis A skeleton to show that the stereoselectivity and yield can be accurately estimated. [ABSTRACT FROM AUTHOR]

Chemical synthesis is one of the practical approaches to access carbohydrate‐based natural products and their derivatives with high quality and in a large quantity. However, stereoselectivity during the glycosylation reaction is the main challenge because the reaction can generate both α‐ and β‐glycosides. The main focus of the present article is the concept of recent mechanistic studies that have applied statistical analysis and quantitation for defining stereoselective changes during the reaction process. Based on experimental evidence, a detailed discussion associated with the mechanism and degree of influence affecting the stereoselective outcome of glycosylation is included. [ABSTRACT FROM AUTHOR]

Stereocontrolled chemical glycosylation remains a major challenge despite vast efforts reported over many decades and so far still mainly relies on trial and error. Now it is shown that the relative reactivity value (RRV) of thioglycosides is an indicator for revealing stereoselectivities according to four types of acceptors. Mechanistic studies show that the reaction is dominated by two distinct intermediates: glycosyl triflates and glycosyl halides from N‐halosuccinimide (NXS)/TfOH. The formation of glycosyl halide is highly correlated with the production of α‐glycoside. These findings enable glycosylation reactions to be foreseen by using RRVs as an α/β‐selectivity indicator and guidelines and rules to be developed for stereocontrolled glycosylation. [ABSTRACT FROM AUTHOR]

Keywords: carbohydrates; diastereoselectivity; glycosylation; synthesis design; statistical analysis EN carbohydrates diastereoselectivity glycosylation synthesis design statistical analysis 1 1 1 02/08/21 20210205 NES 210205 B The stereoselectivity and yield of glycosylation reactions b are influenced by numerous intrinsic and environmental factors. This Concept article by C.-C. Wang and colleagues on page 2556 introduces the recent achievements on the statistical analysis to glycosylation reactions. Carbohydrates, diastereoselectivity, glycosylation, synthesis design, statistical analysis. [Extracted from the article]