2‐Nitroglycals: Versatile Building Blocks for the Synthesis of 2‐Aminoglycosides

Abstract

Abstract2‐Deoxy‐2‐amino‐substituted glycosides are ubiquitous compounds in biochemistry and biology. Therefore, the development of new synthetic pathways to access natural and non‐natural derivatives is highly desirable. In that context, 2‐nitroglycals appeared as versatile building blocks for reaching those targets. Since their first introduction almost forty years ago, their synthetic utility has been widely demonstrated and they have been used to access natural and non‐natural compounds with potent biological activity. The aim of this review is to summarize the developed routes to these versatile intermediates as well as their reactivity. The main applications of the chemistry developed with 2‐nitroglycal derivatives is also highlighted in this first review.

A General Strategy for the Stereoselective Synthesis of Pyrrole‐Fused Chiral Skeletons: [3+2] Cycloaddition with 2‐Nitro‐2,3‐Unsaturated Glycosides

“…[13] However, only a few studies have reported the synthesis of 2-nitro-2,3-unsaturated glycosides [14] from 2nitroglycal. [15] Vankar et al synthesized 2-nitro-2,3-unsaturated glycosides by using DMAP as an effective catalyst, and provided 10 substrates. Thus, efforts are still needed to develop a general methodology that can provide a direct and rapid access to 2nitro-2,3-unsaturated glycosides.…”

“…The Ferrier rearrangement of glycals is the most common methodology to obtain these glycosides [13] . However, only a few studies have reported the synthesis of 2‐nitro‐2,3‐unsaturated glycosides [14] from 2‐nitroglycal [15] . Vankar et al .…”

Stereoselective Glycosylation of 2-Nitrogalactals Catalyzed by a Bifunctional Organocatalyst

“…However, despite many efforts in the area, the synthesis of 1,2- cis aminoglycosides still remains particularly difficult since most common N -protecting groups (e.g., amides, carbamates) exhibit 1,2- trans -directing behavior during the glycosylation reaction favoring the formation of β-linked products . 2-Nitroglycals have been shown to be useful glycosyl donors for the synthesis of aminoglycosides whereby the nitro group serves as a nonparticipating latent amino functionality. − Base-catalyzed conjugation of alcohols to 2-nitroglycals has been reported by the Schmidt group for forming α- and β-linked 2-amino-2-deoxy- O -glycosides . Moreover, the α/β-selectivity of this concatenation reaction is highly dependent on the nature of the base and nucleophile employed in the reaction. ,− …”

Synthesis of 2‐Substituted Thioglycals from Carbohydrate‐Derived Ketene Dithioacetals

“…Despite several attempts, alkylation with some methylating agents (MeI/AgNO 3 , MeOTf, Meerwein's salt) or halogenation with N ‐halogenosuccinimides were unsuccessful. 2‐Nitroglycals have been recognized as very useful glycosyl donors for Michael additions, Diels‐Alder reactions, or [3+2] cycloadditions . However, nitration of thioglycal 3 , under various experimental conditions, did not work.…”