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