2‐Isoxazolines: A Synthetic and Medicinal Overview

Abstract

Isoxazolines are nitrogen‐ and oxygen‐containing five‐membered heterocyclic scaffolds with extensive biological activities. This framework can be readily obtained in good to excellent yields through 1,3‐dipolar cycloaddition between nitrones with alkynes or allenes, aryl/alkyl halides, alkynes, and oxaziridines under mild conditions. This scaffold has been an emerging area of interest for many researchers given their wide range of bioactivities. Herein we review synthetic strategies toward isoxazolines and the role these efforts have had in enhancing the biological activity of natural products and synthetic compounds such as antitubercular agents, COX‐1 inhibitors, COX‐2 inhibitors (e. g., valdecoxib), nicotinic receptor modulators, and MIF inhibitors. With a focus on efforts from 2010 onward, this review provides in‐depth coverage of the design and biological evaluation of isoxazoline systems and their impact on various pathologies.

Synthesis of 5-Vinyl-2-isoxazolines by Palladium-Catalyzed Intramolecular O-Allylation of Ketoximes

“…Isoxazolines are nitrogen- and oxygen-containing five membered heterocycles which are versatile motifs present in many important natural products and bioactive compounds . These are also used as chiral ligands in many asymmetric catalytic transformations .…”

Applications of Oxone® in Organic Synthesis: An Emerging Green Reagent of Modern Era

“…Isoxazoles and isoxazolines are found in numerous natural as well as non-natural products with a varied biological activities, such as anticancer, antifungal, anticonvulsant, antiviral, antibacterial, antidepressant, antiinflammatory, and insecticidal activity etc. [291,[295][296][297][298][299][300] To that context, recently, [3 + 2]-cycloaddition strategy was successfully effected by Tong's group to assemble isoxazoline and isoxazole derivatives 373 a-f by means of in-situ generated nitrile oxides from the aldoximes 371through the oxone/NaCl oxidation followed by the 1,3-dipolar cycloaddition with different alkenes/alkynes 372(Scheme 120). [301] The detailed mechanistic pathway for this crucial protocol is systematically described in the Scheme 121.…”

Diversity-Oriented Synthesis of Highly Functionalized Alicycles across Dipolar Cycloaddition/Metathesis Reaction

“…Kotain et al synthesized isoxazoline-based derivatives, which were screened for their antibacterial activities. Compound 132 was found to show outstanding inhibition against both tested Gram-negative strains (K. pneumonia and E. coli) 19,[82][83][84][85][86][87][88][89][90] (Figure 12). In order to prepare fluorine-containing compounds, the development of efficient synthetic methods applicable to fluorine-containing organic compounds is necessary.…”

“…The synthesis of highly functionalized cyclopentane derivatives gained considerable attention in medicinal chemistry, as a result of their various biological activities. [15][16][17][18][19][20][21][22][23][24] Some isoxazoline derivatives were earlier synthesized starting from various cyclic -amino acids by applying regio-and stereoselective 1,3-dipolar cycloaddition of nitrile oxide. [24][25][26][27][28][29] Moreover, cyclic -amino This document was downloaded for personal use only.…”