Statistical Analysis of Glycosylation Reactions

Abstract

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.

Towards a Systematic Understanding of the Influence of Temperature on Glycosylation Reactions

“…[3] Reported yields can be difficult to reproduce, and crucial reaction conditions often go unreported. Despite recent advances in the standardization of glycosidic bond formation, as well as an improved physical organic and mechanistic understanding of the factors governing the outcomes, [4][5][6][7][8][9] irreproducibility and poor transferability stymie progress. Here, we aim to decrypt the fundamental role of temperature, a key parameter influencing the yield and selectivity of glycosylations.…”

Thiocarbonyl as a Switchable Relay-Auxiliary Group in Carbohydrate Synthesis

“…According to our previous works, − stereoselective glycosylation was highly associated with the reactivity of the glycosyl donor and acceptor. Therefore, to systematically investigate the participating ability of the C 6-acyl group, it is necessary to consider the electronic, steric, and conformational contributions of coupling partners.…”

“…The stereoselectivity outcome has been found to be elusive with different functionalities/reactivities of donors. At least 11 environmental influences can potentially modulate the oxocarbenium ion intermediates, resulting in the formation of a mixture of β or α conformers. − We have previously reported a quantitative system to summarize the effect of building blocks and the promoter. − A synthetic protocol of glycosylation was further established to enable researchers to achieve a high yield of 1,2- cis glycosylation.…”

“…Second, the C 6-carbonylation can be controlled with different activators, and this switchable character allows a concise synthesis for both 6-OH glycoside 17 and 6-deoxy glycoside 18 individually. Third, on the basis of statistical analysis, we quantified and further analyzed the participating ability of the C 6-acyl group during glycosylation using our reactivity-based platform. − The numeric parameters clearly indicated a higher contribution of the thiocarbonyl group in comparison to the common acetyl (Ac) or benzoyl (Bz) group.…”

Zu einem Systematischen Verständnis des Einflusses der Temperatur auf Glykosylierungsreaktionen

“…In der Praxis werden glykosidische Bindungen hergestellt, indem sie unzählige Glykosylkupplungspaare (Glykosylierungsmittel und Nukleophil), Promotorsysteme, Lösungsmittel und Konzentrationen verwenden und sich dabei auf kaum unterschiedliche Temperaturregime verlassen [3] . Trotz jüngster Fortschritte bei der Standardisierung der Bildung glykosidischer Bindungen sowie eines verbesserten physikalisch‐organischen und mechanistischen Verständnisses der Faktoren, die die Ergebnisse bestimmen, [4–9] behindern Unreproduzierbarkeit und schlechte Übertragbarkeit den Fortschritt. Hier wollen wir die grundlegende Rolle der Temperatur ermitteln, einem Schlüsselparameter, der die Ausbeute und Selektivität von Glykosylierungen beeinflusst.…”