Versatile approach to densely substituted isoxazolines and pyrazolines: Focus on a quaternary carbon center as a constitutive feature

Abdelli, Abderrahmen; Gharsa, Haythem; Jmaï, Momtez; Gaucher, Anne; M'rabet, Hedi; Prim, Damien

doi:10.1016/j.tetlet.2020.151958

Cited by 11 publications

(10 citation statements)

References 42 publications

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“…In another 2020 article, Abdelli et al described regioselective cycloaddition of in situ-generated (from oxymoyl chloride) nitrile oxide to 2-ethoxycarbonyl allyl phosphonates leading to 3,5,5-trisubstituted 2-isoxazolines— Scheme 250 [ 264 ].…”

Section: Syntheses Of Substituted 2-isoxazolines Via 13-dp Cycloaddit...mentioning

confidence: 99%

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Nitrile Oxide, Alkenes, Dipolar Cycloaddition, Isomerization and Metathesis Involved in the Syntheses of 2-Isoxazolines

et al. 2023

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The involvement of 1,3-dipolar cycloaddition (1,3-DP), double bond migration, metathesis, and nitrile oxide (including in situ-generated nitrile oxide) as dipoles, together with the C=C bond containing dipolarophiles, in the syntheses of 2-isoxazolines is presented. Methods for synthesizing isoxazolines (other than 1,3-DP cycloaddition) were also presented briefly. Various methods of nitrile oxide preparation, especially in situ-generated procedures, are presented. Special attention was paid to the application of various combinations of 1,3-DP cycloaddition with double bond migration (DBM) and with alkene metathesis (AM) in the syntheses of trisubstituted isoxazolines. Allyl compounds of the type QCH2CH=CH2 (Q = ArO, ArS, Ar, and others) play the role of dipolarophile precursors in the combinations of DPC mentioned, DBM and AM. Mechanistic aspects of cycloadditions, i.e., concerted or stepwise reaction mechanism and their regio- and stereoselectivity are also discussed from experimental and theoretical points of view. Side reactions accompanying cycloaddition, especially nitrile oxide dimerization, are considered. 2-Isoxazoline applications in organic synthesis and their biological activity, broad utility in medicine, agriculture, and other fields were also raised. Some remaining challenges in the field of 1,3-DP cycloaddition in the syntheses of isoxazolines are finally discussed.

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Section: Syntheses Of Substituted 2-isoxazolines Via 13-dp Cycloaddit...mentioning

confidence: 99%

“… Syntheses of trisubstituted 2-isoxazolines equipped with P(O)(OEt) 2 motif via DP cycloaddition of in situ-generated nitrile oxide to ethoxycarbonyl allylphosphonates [ 264 ].] R = Et, Me; Ar = Ph, p -MeC 6 H 4 , 2,3-(MeO) 2 C 6 H 3 ; a = Et 3 N, CHCl 3 , rt, 18 h; up to 82% yield.…”

Section: Figures and Schemesmentioning

confidence: 99%

Nitrile Oxide, Alkenes, Dipolar Cycloaddition, Isomerization and Metathesis Involved in the Syntheses of 2-Isoxazolines

et al. 2023

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“…Our novel approach allows the formation of a ternary C3 center on both families of heterocycles and the installation of a valable methylphosphonate moiety at this same position. [11] Finally, the evaluation of ACE inhibition activity of selected δ-lactams and glutarimides is reported…”

Section: Introductionmentioning

confidence: 99%

Synthesis and evaluation of new phosphonated δ‐lactam and glutarimide derivatives as angiotensin converting enzyme inhibitors

Abdelli

Bejaoui

Bougatef

et al. 2022

Journal of Heterocyclic Chem

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An efficient synthesis of new γ,δ‐insaturated δ‐lactam and glutarimide derivatives bearing a phosphonomethyl group from a common allylphosphonate precursor is described. Our approach is based on a two‐step procedure involving the preparation of phosphonated‐1,5‐ketoester and −1,5‐diester followed by an amidation–heterocyclization sequence. The first step proceeds via Michael's addition of ethyl acetoacetate and diethyl malonate on an allylphosphonate starting material. The second step consists of a base‐promoted intramolecular amidation‐cyclization sequence with primary amines, which accounts for the construction of δ‐lactams and glutarimide skeletons. We performed the evaluation of angiotensin I‐converting enzyme (ACE) inhibition using an in vitro enzyme assay on six new compounds. Five compounds showed potent ACE inhibitory activity, with IC50 values ranging from 0.02 to 0.27 mg/ml. Compared with Captopril, used as a reference drug, two new glutarimide derivatives exhibited higher efficiency ACE inhibition activity.

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“…Our research teams have specialized in the synthesis of several families of new biologically relevant heterocyclic compounds. Recent works have shown that condensed pyrimidines, isoxazolines, and pyrazolines exhibit significant antibacterial activity [ 11 , 12 , 13 ]. Other studies were devoted to the development of heterocyclic systems as quorum sensing modulators, including tetrazole and furanone derivatives ( Figure 1 ) [ 14 , 15 ].…”

Section: Introductionmentioning

confidence: 99%

Heterocyclic Chemistry Applied to the Design of N-Acyl Homoserine Lactone Analogues as Bacterial Quorum Sensing Signals Mimics

Zhang

Hachicha

et al. 2021

Molecules

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N-acyl homoserine lactones (AHLs) are small signaling molecules used by many Gram-negative bacteria for coordinating their behavior as a function of their population density. This process, based on the biosynthesis and the sensing of such molecular signals, and referred to as Quorum Sensing (QS), regulates various gene expressions, including growth, virulence, biofilms formation, and toxin production. Considering the role of QS in bacterial pathogenicity, its modulation appears as a possible complementary approach in antibacterial strategies. Analogues and mimics of AHLs are therefore biologically relevant targets, including several families in which heterocyclic chemistry provides a strategic contribution in the molecular design and the synthetic approach. AHLs consist of three main sections, the homoserine lactone ring, the central amide group, and the side chain, which can vary in length and level of oxygenation. The purpose of this review is to summarize the contribution of heterocyclic chemistry in the design of AHLs analogues, insisting on the way heterocyclic building blocks can serve as replacements of the lactone moiety, as a bioisostere for the amide group, or as an additional pattern appended to the side chain. A few non-AHL-related heterocyclic compounds with AHL-like QS activity are also mentioned.

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Versatile approach to densely substituted isoxazolines and pyrazolines: Focus on a quaternary carbon center as a constitutive feature

Cited by 11 publications

References 42 publications

Nitrile Oxide, Alkenes, Dipolar Cycloaddition, Isomerization and Metathesis Involved in the Syntheses of 2-Isoxazolines

Nitrile Oxide, Alkenes, Dipolar Cycloaddition, Isomerization and Metathesis Involved in the Syntheses of 2-Isoxazolines

Synthesis and evaluation of new phosphonated δ‐lactam and glutarimide derivatives as angiotensin converting enzyme inhibitors

Heterocyclic Chemistry Applied to the Design of N-Acyl Homoserine Lactone Analogues as Bacterial Quorum Sensing Signals Mimics

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