Showing papers on "Glycal published in 2020"

Direct N-Glycosylation of Amides/Amines with Glycal Donors

Abstract: Direct N-glycosylation between glycals and amides/amines was achieved with exclusive stereoselectivity in moderate to high yields. Various amides, amines, and 3,4-O-carbonate-glycals were tolerated, and unique β-N-glycosides were obtained. The strategy was based on palladium-catalyzed decarboxylative allylation, and the high 1,4-cis-selectivity was proposed because of the hydrogen bonding effect. Notably, all the synthesized products were subjected to preliminary bioactivity studies, revealing that three compounds were cytotoxic to tumor cells and nontoxic to normal human cells.

Copper(ii)-catalyzed stereoselective 1,2-addition vs. Ferrier glycosylation of "armed" and "disarmed" glycal donors.

Abstract: Selective activation of “armed’ and ‘'disarmed” glycal donors enabling the stereo-controlled glycosylations by employing Cu(II)-catalyst as the promoter has been realized. The distinctive stereochemical outcome in the process is mainly influenced by the presence of diverse protecting groups on the donor and the solvent system employed. The protocol is compatible with a variety of aglycones including carbohydrates, amino acids, and natural products to access deoxy-glycosides and glycoconjugates with high α-anomeric selectivity. Notably, the synthetic practicality of the method is amply verified for the stereoselective assembling of trisaccharides comprising 2-deoxy components. Mechanistic studies involving deuterated experiments validate the syn-diastereoselective 1,2-addition of acceptors on the double bond of armed donors.

Guidelines for β-Lactam Synthesis: Glycal Protecting Groups Dictate Stereoelectronics and [2+2] Cycloaddition Kinetics.

Abstract: The alkene-isocyanate cycloaddition method affords β-lactams from glycals with high regio- and stereoselectivity, but the factors that determine substrate reactivity are poorly understood. Thus, we...

A light- and heat-driven glycal diazidation approach to nitrogenous carbohydrate derivatives with antiviral activity.

Abstract: The aminated mimetics of 2-keto-3-deoxy-sugar acids such as the anti-influenza clinical drugs oseltamivir (Tamiflu) and zanamivir (Relenza) are important bioactive molecules. Development of synthetic methodologies for accessing such compound collections is highly desirable. Herein, we describe a simple, catalyst-free glycal diazidation protocol enabled by visible light-driven conditions. This new method requires neither acid promoters nor transition-metal catalysts and takes place at ambient temperature within 1-2 hours. Notably, the desired transformations could be promoted by thermal conditions as well, albeit with lower efficacy compared to the light-induced conditions. Different sugar acid-derived glycal templates have been converted into a range of 2,3-diazido carbohydrate analogs by harnessing this mild and scalable approach, leading to the discovery of new antiviral agents.

Copper-Catalyzed Stereoselective Synthesis of 2-Deoxygalactosides

Abstract: An efficient glycosylation method to synthesize 2-deoxy-O-galactosides based on a Cu(II)-catalyzed reaction without additional ligand has been developed. The glycosylation was amenable to different protected glycal donors and a wide range of acceptors including alcohols, amino acids, sugars, and phenol, and proceeds with excellent yield and high α-selectivity under mild conditions. The reaction proceeds readily on a gram scale, and its versatility is exemplified in the synthesis of oligosaccharides.

Synthesis of C-glycosyl phosphonate derivatives of 4-amino-4-deoxy-α-ʟ-arabinose.

Abstract: The incorporation of basic substituents into the structurally conserved domains of cell wall lipopolysaccharides has been identified as a major mechanism contributing to antimicrobial resistance of Gram-negative pathogenic bacteria. Inhibition of the corresponding enzymatic steps, specifically the transfer of 4-amino-4-deoxy-ʟ-arabinose, would thus restore the activity of cationic antimicrobial peptides and several antimicrobial drugs. C-glycosidically-linked phospholipid derivatives of 4-amino-4-deoxy-ʟ-arabinose have been prepared as hydrolytically stable and chain-shortened analogues of the native undecaprenyl donor. The C-phosphonate unit was installed via a Wittig reaction of benzyl-protected 1,5-arabinonic acid lactone with the lithium salt of dimethyl methylphosphonate followed by an elimination step of the resulting hemiketal, leading to the corresponding exo- and endo-glycal derivatives. The ensuing selective monodemethylation and hydrogenolysis of the benzyl groups and reduction of the 4-azido group gave the α-ʟ-anomeric arabino- and ribo-configured methyl phosphonate esters. In addition, the monomethyl phosphonate glycal intermediates were converted into n-octyl derivatives followed by subsequent selective removal of the methyl phosphonate ester group and hydrogenation to give the octylphosphono derivatives. These intermediates will be of value for their future conversion into transition state analogues as well as for the introduction of various lipid extensions at the anomeric phosphonate moiety.

Unexpected Formation of Oxetanes during the Synthesis of Dodeco-6,7-diuloses

Abstract: During the synthesis of symmetrical dodeco-6,7-diuloses that are potential candidates for inhibition of glycosidases, an unanticipated epoxide-oxetane rearrangement was observed. A bicyclic sugar consisting of a glycal moiety and an anomeric esterified furanose was oxidized under epoxidation conditions (mCPBA/KF). The isolation of the pure epoxide was not possible since a rapid reversible conversion accompanied by the migration of the ester group took place and resulted in the formation of an unusual oxetane-bridged disaccharide scaffold. X-ray diffractometric structure elucidation and the suggested mechanism of the rearrangement are provided.