Pyranose N-Glycosyl Amines: Emerging Targets With Diverse Biological Potential

Abstract

Interest in the chemistry and biological properties of non-nucleoside N-glycosidic compounds has gathered pace over the past several years; the occurrence of the N-glycoside moiety in glycoproteins and a range of active natural products has prompted the synthesis of a diverse spectrum of related materials with promising potential in medicinal chemistry. Particularly prominent has been the synthesis of novel N-glycosyl amides, 1,2,3-triazoles, and progress in the construction and diversification of natural products such as the mannopeptimycins and indolocarbazoles, each of which are discussed in this article.

Synthesis and Antiprotozoal Activity of Cationic 1,4-Diphenyl-1H-1,2,3-triazoles

“…68, 69 Because of its high regioselectivity, mild reaction conditions, and excellent yields of desired products, the copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) has found multiple applications in material science, bioconjugate chemistry, and drug discovery. 70-76 …”

“…68,69 Because of its high regioselectivity, mild reaction conditions, and excellent yields of desired products, the copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) has found multiple applications in materials science, bioconjugate chemistry, and drug discovery. [70][71][72][73][74][75][76] In our search for novel safer and more potent antiprotozoal drug candidates, we herein report the synthesis of novel cationic 1,4-diphenyl-1,2,3-triazoles 1-60 utilizing the CuAAC methodology. Compounds 1-60 were evaluated in vitro for antiprotozoal potency versus T. brucei rhodesiense (STIB900), chloroquine resistant Plasmodium falciparum (K1), axenic amastigotes of Leishmania donovani (MHOM/SD/62/ 1S-CL2 D ) and for cytotoxicity against rat myoblast cells (L6).…”

“…Among several possible ways to construct the five-membered triazole ring, the most suitable for us was the Huisgen 1,3-dipolar cycloaddition of organic azides to terminal alkynes. This method, which normally required prolonged usage of elevated temperatures and usually afforded mixtures of 1,4- and 1,5-disubstituted 1,2,3-triazoles, , has been recently revitalized by the discovery that Cu(I) salts facilitate the addition of azides to alkynes at ambient temperature, affording exclusively 1,4-disubstituted isomers. , Because of its high regioselectivity, mild reaction conditions, and excellent yields of desired products, the copper(I)-catalyzed azide−alkyne cycloaddition (CuAAC) has found multiple applications in materials science, bioconjugate chemistry, and drug discovery. − …”

Guanidinylation of Chitooligosaccharides Involving Internal Cyclization of the Guanidino Group on the Reducing End and Effect of Guanidinylation on Protein Binding Ability

“…The reducing end showing high reactivity is an attractive target to achieve a protection-free synthesis of valuable building blocks. The production of glycosyl amines [13], glycosyl azides [14], and glycosyl donors [15,16,17], and the immobilization of carbohydrate building block via reductive amination [18], by virtue of the high reactivity of the reducing end, are widely employed in carbohydrate chemistry. The development of protection-free synthesis for making building blocks that still require the protection–deprotection process is effective for developing medicines, agrochemicals, and functional materials.…”

Allyl Cyanate/Isocyanate Rearrangement in Glycals: Stereoselective Synthesis of 1-Amino and Diamino Sugar Derivatives

“…Several synthetic efforts have been devoted to accessing diverse N -glycosides (amides, ureas, heterocycles), in view of their potential for medicinal chemistry. , However, compared to O - and C -glycosides, efficient and stereoselective syntheses of N -glycosides are less investigated and remain challenging. − , Major issues are formation of anomeric mixtures and configurational stability. Selectivity for a single anomer is an important target and represents a substantial synthetic challenge.…”