Methods for 2-Deoxyglycoside Synthesis

Abstract

Deoxy-sugars often play a critical role in modulating the potency of many bioactive natural products. Accordingly, there has been sustained interest in methods for their synthesis over the past several decades. The focus of much of this work has been on developing new glycosylation reactions that permit the mild and selective construction of deoxyglycosides. This Review covers classical approaches to deoxyglycoside synthesis, as well as more recently developed chemistry that aims to control the selectivity of the reaction through rational design of the promoter. Where relevant, the application of this chemistry to natural product synthesis will also be described.

Structural and Computational Analysis of 2‐Halogeno‐Glycosyl Cations in the Presence of a Superacid: An Expansive Platform

“…[1] This important class of carbohydrates appears frequently in bioactive natural products, [2] but stereocontrolled glycosidic bond formation remains challenging. Inclusion of af unctional handle at C2 allows glycosylation to be influenced in atraceless fashion, rendering them ideal to access 2-deoxyglycosides.…”

Direct Addition of Amides to Glycals Enabled by Solvation‐Insusceptible 2‐Haloazolium Salt Catalysis

“…[7,8] Thus,a2-deoxyglycosylation of the Asn residues could give the peptide chain stability against hydrolysis,r esulting in enhanced biological activity and selectivity [9] (Figure 1A). [12] Therefore,t he direct 2-deoxyglycosylation of hydroxyl groups [13,14] (Figure 1B,E q. [10,11] The direct 2-deoxyglycosylation of nucleophiles with glycals is one of the most straightforward approaches to 2-deoxysugar compounds.…”

“…In this paper,wereport the first example of the direct 2-deoxyglycosylation of an amide group with our newly designed 2-halogenated azolium salts as Brønsted acids.The salient features of this method are as follows:1)the formation of the azolium salt enabled am ild condition, and [*] Y. Nakatsuji, Dr.Y . We initially investigated the reaction conditions used for the direct 2-deoxyglycosylation of hydroxyl groups, [12] and tested the ability of various acid catalysts to promote the 2deoxyglycosylation of amides with the typical galactal substrate 1 as am odel reaction (Table 1). [18] Furthermore,d uring the course of our investigations,i tw as found that the acid catalysts were inhibited by the amide groups.Detailed mechanistic investigations suggested that the halogen atom and the extended p-scaffold of our new catalyst played an important role for the improved catalytic activity, even in the presence of amides.…”

“…Although the donor 1 was completely consumed at 70 8 8C, the yield of 2a was not significantly improved owing to the degradation of donor 1, affording byproduct 3 (entry 3). Notably,the use of the catalyst C·TfOH without ahalogen atom (entry 11) and the benzoimidazolium catalyst E·TfOH (entry 13) significantly decreased the yield of 2a, strongly indicating that both the halogen atom and the azolium cation scaffold played an important role in the catalytic activity (entries [9][10][11][12][13][14][15]. An effective phosphoric acid catalyst for the O-glycosylation reaction [19] could not promote the 2deoxyglycosylation of amides (entry 5).…”

“…An effective phosphoric acid catalyst for the O-glycosylation reaction [19] could not promote the 2deoxyglycosylation of amides (entry 5). [12] The predominant b-selectivity could be explained by the exoanomeric effect [20] (Supporting Information, Figure S13). Strong Brønsted acid and Lewis acid catalysts,such as triflic acid (TfOH) and BF 3 ·OEt 2 , could completely consume the glycosyl donor 1,but the yields of 2a were still not improved because of ac onsiderable amount of byproducts.T he benzyl alcohol adduct 3 was isolated as amajor byproduct, implying that astrongly acidic or heated condition caused the degradation of the glycal 1 through, for example,t he Ferrier reaction (entries 3,7,8).…”