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Synthesis of Novel 5-(alk-3-enyl)-hydantoins
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1  Faculty of Science, University of Kragujevac, Radoja Domanovica 12 P.O. Box 60, 34000 Kragujevac, Serbia

Abstract: The hydantoin moiety occurring in various biologically active compounds represents a pharmaceutical importance most notably known due to their antimicrobial, anticancer and anticonvulsant activity1,2. The observed activities usually do not arise from the heterocycle itself but from the different ligands that have been attached to it, especially in the position C5. This led us to prepare a series of the novel structural analogues with varying alkenyl substitution patterns on C5. In the multicomponent reaction under Bucherer-Bergs conditions, construction of 5-(alk-3-enyl)-hydantoins were made in good yields starting from unsaturated aldehydes, ketones and β-ketoesters. Some of them were substituted with alkyl groups at N3 position via selective N-alkylation reaction by reacting alkyl halides in the presence of KOH and methanol as a solvent. When allyl-β-ketoesters were used for the synthesis of hydantoins an unexpected decarboxylation were observed. Decarboxylation was not observed only when 2-allyl-ethylacetoacetate was used as the substrates while in other cases fully decarboxylated products were obtained. All alkenyl hydantoins were characterized by elemental analyzes, FTIR, 1H and 13C NMR spectroscopy. This alkenyl hydantoins could serve as useful precursors for further modification, especially for the synthesis of bicyclic hydantoins. Moreover, substituted hydantoins are important building blocks for the synthesis of nonnatural amino acids. 1. J. C. Thenmozhiyal, P. T. Wong, W. Chui, J. Med. Chem., 47 (2004) 1527 2. A. Volonterio, C. R. de Arellano, M. Zanda, J. Org. Chem., 70 (2004) 2161
Keywords: Bucherer-Bergs reaction, hydantoins, alkylation