Nucleophilic Ring‐Opening of 1,6‐Anhydrosugars: Recent Advances and Applications in Organic Synthesis

Abstract

Anhydrosugars provide a valuable source of building blocks for the synthesis of a wide range of compounds of interest, from natural products to medicines. The unique reactivity of these functionalized, homochiral synthons is controlled by the 1,6-anhydro bridge which locks the conformation of the pyranose ring, provides a dual protection of two hydroxyl groups, and either protects or activates the anomeric position. The concomitant release of the primary hydroxyl group at C-6 during the ring-opening step limits protecting group manipulations and enables the design of highly convergent synthetic strategies. In recent years, many examples of stereocontrolled ring-opening of 1,6-anhydrosugars by a diversity of nucleophiles, including hetero-and C-nucleophiles, have been reported. The purpose of this review is to present an overview of the recent advances, applications and challenges associated with this process.

From Sweet Molecular Giants to Square Sugars and Vice Versa

“…We envisioned that the stereocontrolled ring-opening of the anhydro bridge would lead to the desired activated sugar building blocks. 87 The concomitant release of a differentiated primary hydroxy group at C-6 would be the icing on the cake, allowing late-stage functionalization of the maltose-base scaffolds. But first, we needed to undertake studies to determine if the reaction was feasible and able to furnish the desired glycosyl azide in good yields and high diastereoselectivity.…”

Recent Applications of Hexamethyldisilathiane (TMS2S) in Organic Synthesis

“…16 TMS 2 S has also found application in glycochemistry as a nucleophile. In 2011, Zhu et al reported an efficient method for the synthesis of α-glycosyl thiols through TMS 2 S ring opening of 1,6-anhydrosugars 17 in the presence of TMSOTf. 18 A few years later, it was discovered by serendipity that this process could be extended to the synthesis of dithioacetal-α,α-diglycosides by adding a ketone or an aldehyde to the reaction media (Table 1 , D).…”

Stereoselective Synthesis of Glycosyl Cyanides by TMSOTf‐Mediated Ring Opening of 1,6‐Anhydro Sugars

“…As an alternative to ionic routes, 1‐ C ‐cyanoglycosides are also obtained via pseudoanomeric radicals generated from glycosyl bromides or glycosyl dithiocarbonates [11] . In recent years, many research groups have exploited the unique reactivity of 1,6‐anhydrosugars in ring‐opening reactions with a diversity of nucleophiles including N ‐, S ‐, and C ‐nucleophiles [12] . Quite surprisingly, no systematic study has been performed so far to study the anomeric cyanation of 1,6‐anhydrosugars in the presence of a cyanide source [13,14] …”

“…First because anomeric cyanation is one of the most simple, practical C ‐extension methods to access C ‐glycosides. Secondly, 1,6‐anhydrosugars offer numerous advantages as sugar donors [12] . The preparation of diversely functionalized 1,6‐anhydrosugar substrates is facilitated by the dual protection of both C‐1 and C‐6 positions and by the differing reactivity of the remaining secondary hydroxy groups due to the locked conformation imposed by the 1,6‐anhydro bridge.…”