In addition, the nucleophilic addition of 1,3-disubstituted barbituric acid to different electrophiles has been applied to prepare highly functionalized spirobarbiturate scaffolds.
Due to the importance of barbiturate-based olefins as activated alkenes, these substrates have been utilized in many reactions. Since 1900, numerous studies have exploited the synthesis of various spirobarbiturate-fused carbo- and heterocycles by applying different strategies. Spiro-connected hexahydropyrimidine-2,4,6-trione heterocyclic rings have received increasing attention from the viewpoint of biological activity and synthetic methods due to the importance of the rigid heterocyclic system and unique orientation of the functional substituents. The biological studies showed that the derived spiro heterocyclic systems have an inhibitory effect of 50%. Based on the planarity geometry of the Spiro pyrrolizidines, meta-substitution possesses steric hindrance and hence shows less effectiveness compared to para-substitution on the same nucleus, which shows a marginal steric effect. Spiro constituents were found to be much more effective for Gram-positive bacteria due to the stronger lipophilic character of the molecules, and they resulted feasible membrane permeation in a biological system. The functionalized spiro-pyrrolizidines were found to be effective for biological uses by considering their in vitro screening and antimicrobial impacts.
The structural and characteristic chemical components of the as-prepared Spiro compounds were characterized by 1H-NMR, FTIR, and Mass spectroscopy.
The reaction intermediate comprised azomethineylides derived from reactive primary amines, and the spiro derivatives were synthesized up to a ≈ 95% yield. The higher atomic economy with higher yield (95%) and regio and stereoselectivity were achieved by a multi-component reaction of L-proline (1), Indenoquinoxaline (2), and the dipolarophile of malononitrile (3) solvents followed by reflux conditions. In this work, we report a synthesis of spirocyclic compounds under a one-pot reaction using 1,3-dipolar cycloaddition in a regio and diastereoselective manner. Recent advances in functionalized organic Spiro heterocyclic compounds composed of nitrogen bonded five- and six-membered rings have been made, establishing them as a synthetic target in organic-based biomedical applications.
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