Contents
1. Introduction Page No.
2. Ni-catalyzed synthesis of C-glycosides Page No.
2.1. Aryl/vinyl C-glycoside synthesis Page No.
2.2. Acyl C-glycoside synthesis Page No.
2.3. Alkyl C-glycoside synthesis Page No.
3. Conclusions and perspectives Page No.
1. Introduction
Glycosides play a critical role in diverse biological processes,[1] and studies of these carbohydrates are essential for further advancement in fields such as biology, medicine, and pharmacology. [2] Access to significant quantities of well-defined bioactive carbohydrates is a prerequisite for the investigation of the roles of carbohydrates in these areas.[3] In this context, developing methods to chemically forge glycosidic bonds is critical to meet the above demands. In drug discovery endeavors, C -linked glycosides are usually employed as bioisosteres of O - or N -linked glycosides. The synthesis of C -linked glycosides, however, lagged behind theirO - or N -linked counterparts. Stereoselective construction of α- and β-C -glycosides remains an enduring challenge. In recent decades, transition-metal-mediated methods have exhibited remarkable potential in the stereoselective construction of glycosidic bonds, with significant advancements achieved employing gold,[4] copper, [5] iron,[6] palladium, [7] and nickel as catalysts. Among these fields, the Ni-catalyzed reactions displayed tremendous versatility. In this mini-review, we focus on the recent developments in nickel-catalyzed C-glycosylation reactions, given our longstanding interest in Ni-catalyzed glycosylation. This review is divided into two sections based on the type of glycoside products obtained, namely aryl/vinyl C-glycosides, acyl C-glycosides, and alkyl C-glycosides.
2. Ni-catalyzed synthesis of C-glycosides
C-Glycosides are essential, naturally occurring products and medicinal candidates. Being inert to metabolic processing, these compounds have piqued significant interest in areas of medicine and chemical biology. Therefore, many efforts have been made to construct C-glycosides efficiently in a stereoselective manner. This section summarizes recent developments in the nickel-catalyzed synthesis of C-glycosides, including aryl/vinyl, acyl, and alkyl C-glycosides.
2.1. Aryl/vinyl C-glycoside synthesis
In 2008, Gong and Gagné reported a diastereoselective nickel-catalyzed Negishi Cross-Coupling approach to synthesize saturated, fully oxygenated aryl C-glycosides (Scheme 1). [8] To show the generality of the method, various arylzinc reagents and glucosyl bromides were coupled in a β-selective fashion, yielding the corresponding aryl C-glucosides in high yields (3a–3q ). However, aryl cross-coupling partners bearing ortho substituents (3h–3j ) and pyridine-derived zinc reagents (3p )were not as effective. The trans-phenyl vinyl zinc reagent worked, albeit with a low d.r. (α/β=1:1) (3q ). This protocol was also effective with other glycosyl halides (3r–3y ). Whereas the α-D-galactosyl bromides (3s ) produced the β-
Scheme 1 Synthesis of aryl C-glycosides via Ni-catalyzed Negishi Cross-Coupling