Combined Ugi‐4CR/CuAAC Approach to Triazole‐Based Neoglycolipids

Abstract

New glycolipids that feature a carbohydrate/triazole/lipid hybrid architecture were readily produced by a combined multicomponent/click approach. The process comprises the use of the Ugi four‐component reaction to construct double‐lipidic scaffolds that have either alkyne or azide functionalities followed by conjugation to mono‐ and trisaccharides through a CuI‐catalyzed 1,3‐dipolar cycloaddition (click) process. The high chemical efficiency and feasibility of the overall procedure provides new opportunities for the rapid creation and biological screening of libraries of this unique class of Ugi/click glycolipids. Dynamic NMR experiments were performed to evaluate the free energy of activation related to the isomerization of the cis/trans amide bond in these compounds. This is the first time that such multicomponent and cycloaddition processes have been combined for the synthesis of glycolipids.

Recent Advances in the Chemistry of Glycoconjugate Amphiphiles

“…Glycosphingolipids featuring various mono- and trisaccharide moieties were synthesized by a combined multicomponent/click approach [ 40 ]. The ceramide skeleton synthesis involves a fatty acid, a lipidic isocyanide, para formaldehyde and an amine (either alkynyl or azido-amine) in a one-pot Ugi-four component reaction.…”

Design, synthesis, and antitumor activity of novel paeonol derivatives containing the 1,4-benzoxazinone and 1,2,3-triazole moieties

“…Based on all the above considerations and as an extension of our research on the development of novel paeonol derivatives, a new series of paeonol derivatives containing the 1,4-benzoxazinone and 1,2,3-triazole moieties, which could connect more pharmacophores for constructing bioactive and functional molecules, [23][24][25][26][27][28] were synthesized and exhibited preferable inhibitory activity toward human nonsmall cell lung cancer NCI-H1299 cells and human cervical carcinoma HeLa cells.…”

Cytotoxic Activity and Structure–Activity Relationship of Triazole‐Containing Bis(Aryl Ether) Macrocycles

“…Severalr ecent publications strongly demonstratedt he impact of the Ugi 4-CR on diversity-oriented synthesis [15] and, with respect to this work, toward the production of peptidic macrocycles with miscellaneous potentialb iological activities. [16] Furthermore, the Ugi 4-CR/CuAAC protocol has been used in the construction of several macrocyclic structures with anticancer and antiepilepticp roperties, [17] complex triazole-based neoglycolipids, [18] and fused triazolo derivatives. [19] Herein, we extend our previously reported protocol for the synthesis of ac ollection of bis(aryle ther) macrocycles ( Figure 2) and determinet he plausible application thereof in cancer treatment.…”

“…Several recent publications strongly demonstrated the impact of the Ugi 4‐CR on diversity‐oriented synthesis and, with respect to this work, toward the production of peptidic macrocycles with miscellaneous potential biological activities . Furthermore, the Ugi 4‐CR/CuAAC protocol has been used in the construction of several macrocyclic structures with anticancer and antiepileptic properties, complex triazole‐based neoglycolipids, and fused triazolo derivatives …”