Chiral Isoxazole Research Articles

Lewis Acid Catalyzed (3+2)‐Cycloadditions of Chiral Pyrimidinyl‐Substituted Cyclopropanes with Nitrosoarenes or Silyl Enol Ethers

AbstractChiral isoxazole and carbocyclic pyrimidine nucleoside analogues were synthesized via (3+2)‐cycloadditions of chiral pyrimidinyl‐substituted dimethyl cyclopropanedicarboxylates. In the presence of MgI2, (3+2)‐cycloadditions of chiral pyrimidinyl‐substituted cyclopropanes with nitrosoarenes afforded diverse chiral isoxazole pyrimidine nucleoside analogues in up to 78 % yield and 88–96 % ee. Using Nd(OTf)3 as the catalyst, the annulation reaction with silyl enol ethers generated a series of chiral carbocyclic pyrimidine nucleoside analogues in up to 64 % yield, >20 : 1 dr, and 87–96 % ee. The proposed methods either reduced or avoided partial racemization.

Diastereoselective synthesis and cytotoxic evaluation of new isoxazoles and pyrazoles with monoterpenic skeleton

New series of chiral isoxazoles and pyrazoles with monoterpenic skeleton, have been efficiently synthesized from naturally occurring (R)-Carvone, using 1,3-dipolar cycloaddition reaction with arylonitrile oxides and diarylnitrilimines. The reaction showed high peri-, and regioselectivity. In the case of diarylnitrilimines, the reaction revealed to be highly diastereoselective. The structure of the newly synthesized adducts were fully established via spectroscopic analysis and X-ray crystallography. A succinct theoretical study was used to explain the diastereoselectivity experimentally observed. All the newly synthesized monoterpenic isoxazole and pyrazole derivatives were evaluated for their cytotoxic activity against human HT1080, MCF-7 and A-549 cancer cells.

Enantioselective Vinylogous Amination of 5-Alkyl-4-nitroisoxazoles with a Dipeptide-Based Guanidinium Phase-Transfer Catalyst.

An enantioselective vinylogous amination of 5-alkyl-4-nitroisoxazoles is reported. With a novel chiral dipeptide-based urea-amide-guanidinium as the phase-transfer catalyst, the reactions worked efficiently with NaOAc as the base, affording valuable and challenging-to-synthesize chiral isoxazole derivatives featuring a single stereocenter at the α-position in high yields and with excellent enantioselectivities. Theoretical studies with DFT predicted that cooperative multiple hydrogen-bonding and ion pairing interactions of a nucleophile and NaOAc with the catalyst is crucial to deprotonation by reducing their HOMO-LUMO energy gap.

ChemInform Abstract: Organocatalyzed Asymmetric Vinylogous Michael Reactions of 3,5‐Dialkyl‐Substituted 4‐Nitroisoxazoles: A Direct Method for the Synthesis of Chiral Isoxazole Derivatives.

AbstractVarious highly functionalized chiral isoxazole derivatives are obtained in excellent enantioselectivities by direct asymmetric vinylogous Michael addition of 3,5‐dialkyl‐substituted 4‐nitroisoxazoles with α,β‐unsaturated aldehydes using a diphenylprolinol Tbs ether as organocatalyst.

Organocatalyzed Asymmetric Vinylogous Michael Reactions of 3,5‐Dialkyl‐Substituted 4‐Nitroisoxazoles: A Direct Method for the Synthesis of Chiral Isoxazole Derivatives

AbstractThe direct asymmetric vinylogous Michael addition of 3,5‐dialkyl‐substituted 4‐nitroisoxazoles with α,β‐unsaturated aldehydes catalyzed by a diphenylprolinol TBS ether organocatalyst is described, giving products with moderate to good yields and up to excellent enantioselectivities (96% ee). This approach provides an easy access to highly functionalized chiral isoxazole derivatives.magnified image

ChemInform Abstract: Base‐Catalyzed Isomerization of 2‐Isoxazolines Enables a Two‐Step Enantioselective Synthesis of β‐Hydroxynitriles from Enals.

AbstractTreatment of chiral isoxazoles with catalytic amounts of DBU results in efficient formation of optically active β‐hydroxynitriles.

Preparation of chiral isoxazole carbinols via catalytic asymmetric Corey-Bakshi-Shibata reduction.

A diverse set of isoxazoles, with activity in three different disease categories, was reduced asymmetrically from pro-chiral ketones to chiral alcohols using the Corey-Bakshi-Shibata methodology at the α, β, and γ positions relative to the C-5-methyl of the isoxazole. The experiments described provide an easy route to hydroxylated isoxazoles that represent the common CYP-450 3A4 metabolic site.

Novel chiral isoxazole derivatives: Synthesis and pharmacological characterization at human β-adrenergic receptor subtypes

Isoxazole derivative (±)- 4 and the three pairs of stereoisomeric 3-bromo-isoxazolyl amino alcohols ( S, R)-(−)- 7a/( R, R)-(+)- 7b, ( S, R)-(−)- 8a/( R, R)-(+)- 8b, and ( S, R)-(−)- 9a/( R, R)-(+)- 9b were synthesized and assayed for their affinity and efficacy at human β 1-, β 2-, and β 3-adrenergic receptors (β-ARs) in membranes from Chinese hamster ovary (CHO) cells stably transfected with the respective receptor subtype. Whereas derivative (±)- 4 did not bind at all three β-ARs, stereoisomers ( S, R)- 7a-( S, R)- 9a behaved as high-affinity ligands at β 1- and, particularly, at β 2-ARs ( K i 2.82–66.7 nM). The K i values of isomers ( R, R)- 7b-( R, R)- 9b at β 1- and β 2-subtypes were about 30–100 times higher than those of their ( S, R)- 7a– 9a counterparts, indicating a sizable stereochemical effect. The affinity at β 3-ARs was negligible for all the investigated compounds. When submitted to a functional assay, the three stereoisomeric pairs showed a comparable pattern of efficacy at all three β-AR subtypes. The highest value of efficacy (75–90%) was observed at β 2-ARs, whereas all compounds behaved as partial agonists (30–60%) at the β 3-subtype. The lowest degree of efficacy (15–35%) was found at β 1-ARs. The affinity/efficacy profile of the derivatives under study has been compared with that of the two model compounds, Broxaterol [(±)- 1] and BRL 37344 [(±)- 6].

ChemInform Abstract: Chemoenzymatic Synthesis of Chiral Isoxazole Derivatives.

AbstractCycloaddition reaction of butynone (I) with dibromoacetaldoxime (II) gives the regioisomeric acetylisoxazoles (III) and (IV).

Chemoenzymatic synthesis of chiral isoxazole derivatives

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTChemoenzymatic synthesis of chiral isoxazole derivativesMarco De Amici, Carlo De Micheli, Giacomo Carrea, and Sandro SpeziaCite this: J. Org. Chem. 1989, 54, 11, 2646–2650Publication Date (Print):May 1, 1989Publication History Published online1 May 2002Published inissue 1 May 1989https://doi.org/10.1021/jo00272a037RIGHTS & PERMISSIONSArticle Views721Altmetric-Citations71LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (708 KB) Get e-Alerts Get e-Alerts