Synthesis of spiropyrrolizidines containing quinoxaline and pyrrole fragments

Abstract

The reaction of 1,3-dipolar cycloaddition azomethine ylides obtained by the in situ interaction of 11H-indeno[1,2-b]quinoxalin-11-one and proline, and 3-phenyl-1-pyrrolyl-2-en-1-ones has been used for the synthesis of substituted spiropyrrolizidines in continuation of the study the use of new enones as dipolarophiles. The conditions for the implementation of a three-component synthesis (temperature regime, solvent, activation method) are selected. The best performance has been obtained by refluxing the reaction mixture in ethanol. Ultrasonic activation did not reduce the reaction time or increase the yields significantly. The reaction proceeds regio- and diastereoselectively with the formation of a single type of products in 72–76% yields. It has been found that carrying out the process in the mode of a four-component reaction using ninhydrin and 1,2-phenylphamine, the reaction product of which is 11H-indeno[1,2-b]quinoxalin-11-one, with the selected dipolarophile is impossible due to the formation of ninhydrin azomethine ylide and proline and its interaction with a dipolarophile to give substituted spiro[indene-2,3’- pyrrolysine]-1,3-diones, which has been proven by a counter synthesis using enone, ninhydrin and proline, which also results in the same type products with yields of 89–92%. A probable scheme of the studied transformations is proposed. Regio- and diastereoselectivity testifies in favor of concerted cycloaddition, passing in both cases through a transition state in which a bond is formed between the most electrophilic β-carbon atom of the enone system and the nucleophilic carbon atom of the dipole. The reasons for the observed features are discussed. The composition and structure of the final products have been confirmed by elemental analysis, 1Н, 13С NMR, HMBC, NOESY spectroscopy. The resulting compounds contain pharmacophoric quinoxaline and pyrrole fragments and can be used to study various types of biological activity characteristic of structures with similar fragments.