engleski

Synthesis of N-heterocycles by the three-component Ugi reaction

Multicomponent reactions (MCRs) have attracted significant attention in organic chemistry because of their exceptional ability to implement a wide range of components in one-pot reactions, affording numerous, very diverse products. MCRs are usually very useful in the synthesis of natural products and diverse heterocyclic scaffolds. In particular, isocyanide-based MCRs (IMCRs) are attractive in terms of functional group tolerance and the high levels of chemo-, regio-, and stereoselectivity obtained.[1] Among them, the Ugi four-component reaction (U-4CR) which combines a carbonyl compound, an amine, a carboxylic acid, and an isonitrile is the most prominent. Of particular interest are intramolecular Ugi reactions where one component is a bifunctional building block. These procedures are an efficient tool for the synthesis of nitrogen-containing heterocycles, a versatile building blocks for stereoselective syntheses. On the other hand, these Ugi reaction products possess noteworthy pharmacological activities. [2], [3] In the course of our research, we are interested in utilizing -amino acids and their derivatives as bifunctional components in the Ugi three-component reaction. Herein, we report the succesful use of two different bifunctional amino acid-derived components, Fmoc-Lys-CHO and H-Glu-OMe. In the first case, lysine-derived amino aldehyde undergo intramolecular reaction yielding imine liable to isocyanide addition. In the second set of Ugi reactions, H-Glu-OMe is used, which acts as an amine and a carboxylic acid component. In both cases final products were obtained in moderate to high yields and have the potential for multiple postmodifications.

multicomponent reactions ; Ugi reaction ; hydrazino acids

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