N‐Alkylated C‐Glycosyl Amino Acid Derivatives: Synthesis by a One‐Pot Four‐Component Ugi Reaction

Abstract

C‐glycosides represent an important group of naturally occurring glycosylation derivatives but are also efficient mimetics of native O‐glycosides. Here, a one‐pot four‐component methodology is described toward a library of N‐alkylated C‐glycosyl amino acid derivatives comprising seven different isopropylidene‐protected carbohydrate units. The applied methodology tolerates different amines and isocyanides and provides access to Ugi products in yields up to 85 %. X‐ray analysis of selected products bearing three different carbohydrate motifs and comparison of their crystal structures with similar ones deposited in Cambridge Crystallographic Database revealed that four structures adopt different conformations, mostly not typical for peptide structures. This property opens the possibility to exploit here described N‐alkylated C‐glycosyl amino acid derivatives as templates to access different biotic and abiotic secondary structures.

Sugars in Multicomponent Reactions: A Toolbox for Diversity-Oriented Synthesis

“…The Jeric group 34 synthesized N -alkylated C -glycosyl amino acid derivatives 40 in good yields (up to 99%) via the one-pot, four-component Ugi reaction of isopropylidene-protected sugar-derived aldehydes 35 with different isocyanides 36 , amines 37 , and carboxylic acids 38 (Scheme 7 ). The sugar-derived aldehydes 35 were also reacted with bifunctional derivatives 39 in hexafluoroisopropanol (HFIP) solvent via the Ugi reaction to give more complex structures 41 bearing an additional ring in moderate yields (up to 64%).…”