A review of recent synthetic strategies and biological activities of isoxazole

Abstract

Among different heterocyclic compounds, isoxazole and their analogues are very important classes of heterocyclic compounds as they display an extensive range of biological actions. This makes such scaffolds very important structures in the field of medicinal chemistry. From an extensive literature assessment, isoxazole is clinically proven to be very effective as an anti‐bacterial, anti‐fungal, anti‐inflammatory, anti‐cancer, anti‐tubercular, and anti‐neoplastic agent. The different derivatives of isoxazole which exhibits adjustment in their structure have shown a high degree of variety in their medicinal properties which makes evident them as very beneficial in the progress of novel bioactive drugs which show enhanced effectiveness along with minor harmfulness. Structural aspects of isoxazole having aromaticity with weaker nitrogen‐oxygen bonding provide a potential site for the ring cleavage. Thus, this isoxazole ring system allows easier modifications of substituents in their ring structure which consequently make isoxazole very useful intermediates in various synthetic routes of bioactive compounds. Hence, the synthesis and evaluation of isoxazole‐containing molecules with wider therapeutic consequences are always the topic of interest for chemists. Hence, in light of this comprehensive research on isoxazole, it is thought worthwhile to review various pathways for the synthesis of isoxazole analogues and having a broad spectrum of bioactive actions.

Regioselective Synthesis of Isoxazoles from Propargylic Alcohols via In‐situ‐formed α‐Iodo Enones/Enals

“…Although the structures of products 3 in Table 2 were determined by 1 H NMR analysis after isolation by column chromatography, the difference was very subtle between the 5and 3-substituted isoxazoles, so it was necessary to confirm the structure of products 3 via X-ray diffraction. Accordingly, 3 c was recrystallized from deuterated chloroform, and the structure of 3 c was confirmed unambiguously by X-ray crystallographic analysis (Scheme 3).…”

“…reactions from 3 a to 3 b were attempted, and the results indicated that there is no conversion from 3 a to 3 b (Scheme 6d). The reaction of 2 a to 3 a was monitored by 1 H NMR measurements at 5 min, 20 min, 1 h, and 4 h (see Supporting Information S8 for 1 H NMR spectra). However, no 3 b was detected, indicating that 3 b is not the intermediate in the transformation of 2 a to 3 a, although conversion of 3 b to 3 a is possible (Scheme 6e).…”

“…Isoxazoles are a type of azoles that contain adjacent oxygen and nitrogen heteroatoms. Compounds with isoxazole ring have numerous biological properties, [1] such as anti-cancer, [2] anti-bacterial, [3] anti-fungal, [4] anti-inflammatory, [5] antiproliferative [6] and disinfectant activities. [7] Reactions between hydroxylamine and β-dicarbonyl compounds [8] or α,β-enones [9] are the most frequently used routes to isoxazoles.…”

Isoxazole/Isoxazoline Skeleton in the Structural Modification of Natural Products: A Review

“…Isoxazole is a heterocyclic compound with a five-membered ring that has oxygen and nitrogen atoms at the 1 and 2 positions, and their partially saturated analogs are known as isoxazoline. Many biologically active products contain derivatives of these heterocyclic compounds [ 1 , 2 , 3 ]. Derivatives containing isoxazole/isoxazoline fragments possess biological activities such as anticancer [ 4 , 5 ], anti-inflammatory [ 6 , 7 ], antibacterial [ 8 , 9 ], anti-Alzheimer’s disease [ 10 , 11 ], antioxidant [ 12 , 13 ], insecticidal [ 14 ], antifungal [ 15 , 16 ], and antidiabetic [ 17 , 18 ].…”

Acylmethylidenepyrrolo[1,2-c]oxazoles via [3+2]-cyclization of 2-acylethynylpyrroles with carbonyl compounds

“…Among the fused pyrrole-containing compounds, pyrrolo[1,2- c ]oxazoles combining biologically important pyrrole 2,3 and oxazole 3 cycles remain rare and inaccessible due to the absence of convenient methods for their synthesis. Meanwhile, these bicyclic systems are incorporated in numerous compounds that exhibit pronounced biological activity.…”