Glycosylation reactions are very important reactions in carbohydrate chemistry, leading to the synthesis of oligosaccharides, preferably in a stereoselective manner. The stereoselectivity of these reactions has been shown to be affected by both the nature and the configuration of the protecting group at C-2 on the glycosyl donor ring. While 1,2-trans-glycosides (e.g. α-mannosides and β-glucosides) can be synthesised easily in the presence of a participating group (such as OAc, or NHAc) at the C-2 position in the glycosyl donor ring, 1,2-cis-glycosides are more difficult to prepare. 1,2-cis-glycosides with the α configuration (e.g. glucosides or galactosides) can often be prepared using a non-participating protecting group (such as Bn, or All) on the C-2 hydroxy group. However, 1,2-cis-glycosides with the β configuration are the most difficult to achieve, and present the greatest challenge in glycosylation reactions.
One of the most recent approaches to prepare 1,2-cis-β-glycosides in a stereospecific manner is termed ‘Intramolecular Aglycon Delivery’, and various methods have been developed based on this approach.
In this approach, the glycosyl acceptor is tethered onto the C-2-O-protecting group (X) in the first step. Upon activation of the glycosyl donor group (Y) (usually SR, OAc, or Br group) in the next step, the tethered aglycon traps the developing oxocarbenium ion at C-1, and is transferred from the same face as OH-2, forming the glycosidic bond stereospecifically. The yield of this reaction drops as the bulkiness of the alcohol increases.