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Synthesis of novel peptidomimetics by Passerini reaction

A significant area of organic chemistry is chemical synthesis performed through one–pot mode. [1] Such reactions, known as multicomponent reactions comprise three or more starting reagents and give a single product. The main advantage of multicomponent reactions are an easy access to libraries of complex and structurally diverse compounds starting from relatively simple components. Isocyanide–based multicomponent reactions, eg. Passerini and Ugi reactions are of special importance, because they provide diverse peptide-like compounds. The Passerini reaction is one of the oldest multicomponent reaction used for the construction of α-acyloxyamides-depsipeptides. The reaction involves coupling of aldehyde, carboxylic acid and isocyanide in a nonpolar solvent. [2] We are interested in utilizing multicomponent reactions for the synthesis of conformationally constrained peptidomimetics. The enediyne structural motif (Figure 1) found in natural products with strong anticancer activity 3 was shown to induce -turn or - sheet conformational when incorporated into peptides. Therefore, we decided to use the Passerini reaction for the synthesis of a new class of enediyne-based depsipeptides. Enediyne aldehyde 1, prepared by two consecutive Sonogashira reactions, was coupled with different isocyanides and carboxylic acid in dichloromethane on room temperature (Figure 1). Enediyne depsipeptides were obtained in a 29-92 % yiled.

multicomponent reactions ; Passerini reaction ; Sonogashira reaction

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