Isoxazolidine Derivatives Research Articles

Lanthanide Triflate-Catalyzed Three-Component Coupling Reactions of Aldehydes, Hydroxylamines, and Alkenes Leading to Isoxazolidine Derivatives

Abstract Three-component coupling reactions of aldehydes, hydroxylamines, and alkenes proceeded smoothly in the presence of a catalytic amount of a lanthanide triflate, to afford isoxazolidine derivatives in high yields with high diastereoselectivities. The asymmetric 1,3-dipolar cycloaddition using a chiral lanthanide catalyst is also described.

ChemInform Abstract: Nitrogen Inversion and N‐O Bond Rotation in Some Hydroxylamine and Isoxazolidine Derivatives

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Nitrogen inversion and N–O bond rotation in some hydroxylamine and isoxazolidine derivatives

A series of trisubstituted hydroxylamine derivatives, both cyclic and acyclic, has been prepared. The energy barriers in these hydroxylamines are found to be dominated either by nitrogen inversion or N–O bond rotation depending on the nature of the substituents attached to the nitrogen. In several series of compounds, having XC6H4CH2 substituents attached to nitrogen, Hammett free energy correlations are obtained with positive ρ values, indicating increased electron density at the transition state for the inversion process. Isoxazolidines with C(5) ethoxy substituents demonstrate a strong anomeric effect.

ChemInform Abstract: 1,3‐Dipolar Cycloaddition Reactions of C‐(2‐Nitro)‐styryl‐N‐phenyl Nitrone Leading to the Regiospecific and Stereospecific Synthesis of New Isoxazolidine Derivatives.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

1,3-Dipolar Cycloaddition Reactions of C-(2-Nitro)-styryl-N-phenyl Nitrone Leading to the Regiospecific and Stereospecific Synthesis of New Isoxazolidine Derivatives

Abstract New substituted isoxazolidine derivatives have been synthesized through regiospecific and stereospecific 1,3-dipolar cycloadditions of C-(2-nitro)-styryl-N-phenyl nitrone with reactive dipolarophiles in excellent yields and effects of substituents have been noted.

Synthesis of [3.3.0] bicyclic isoxazolidinyl nucleosides

The isoxazolidine derivative 6, prepared from an intermolecular 1,3-dipolar cycloaddition of the (5 S)-unsaturated lactone 5 and N-methylnitrone, was effectively used for the synthesis of [3.3.0] bicyclic isoxazolidinyl cytidine 4a and thymidine 4b.

Synthesis of chiral cyclic nitrones via a nitrosoketene intermediate and their use for the complete EPC synthesis of nonproteinogenic amino acids

New cyclic chiral nitrones constituting two diastereomers were synthesized by the reaction of isonitroso Meldrum's acid with l-menthone via a nitrosoketene intermediate. Both nitrones reacted with allyltrimethylsilane diastereoselectively to give the corresponding isoxazolidine derivatives as sole products, which converted to ( S)- and ( R)-allylglycines in ca. 100% ee, respectively.

Synthesis of (+)-siphonarienone: Asymmetric alkylation using a chiral benzopyrano-isoxazolidine auxiliary

Asymmetric alkylation of the potassium enolates derived from N-propionyl benzopyrano-[4,3-c]-isoxazolidine derivatives with chiral alkyl triflates proceeded smoothly with high diastereoselectivity. The stereochemistry of the newly formed stereogenic center was fully controlled by the facial selectivity of the enolate according to the rule of double asymmetric synthesis. The application of this methodology led to the first synthesis of (+)-siphonarienone, a marine polypropionate natural product.

Transformations of isoxazolidine and dihydropyran derivatives to optically active compounds

Isoxazolidine and dihydropyran spiro derivatives can be easily transformed, by hydrolysis and hydrogenolysis, to give δ-keto esters, δ-keto acids, β-amino esters, β-amino acids and 3-amino alcohols in good yields. Startiing from optically active compounds enantiomerically pure products are obtained. In some cases, reactions were induced by microwave irradiation.

Intramolecular 1,3-dipolar cycloaddition at the periphery of heterocyclic systems. Part 2. A mechanistic proposal for the facile oxime-nitrone isomerization at the periphery of pyridine and pyrido[1,2- a]pyrimidine systems

The oximes of 4-(alk-2-enylamino)-1,6-dimethyl-2-oxo-1,2-dihydropyridine-3-carbaldehydes and 2-(alk-2-enylamino)-4-oxo-4 H-pyrido[1,2- a]pyrimidine-3-carbaldehydes underwent the thermally induced 1,3-dipolar cycloadditions leading to fused isoxazolidine derivatives under very mild conditions. For the facile oxime-nitrone isomerization, we proposed a mechanistic feature that the alkenylamino nitrogen and/or carbonyl groups in the oximes could play a role as intramolecular catalyst for the consecutive proton transfers on the basis of the thermal behaviors as well as kinetic studies of the oximes isolated.

ChemInform Abstract: Highly Efficient Resolution of Benzopyrano(4,3‐c)isoxazolidine Derivatives: Versatile Chiral Auxiliaries for Asymmetric Alkylation.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Highly efficient resolution of benzopyrano[4,3- c]isoxazolidine derivatives: Versatile chiral auxiliaries for asymmetric alkylation

Benzopyrano[4,3-c]isoxazolidine derivatives, newly developed chiral auxiliaries for asymmetric alkylation, were synthesized and resolved in a unique manner. Resolution could be executed so efficiently that both enantiomers were obtained with a single resolving reagent in excellent yields.

A General Synthetic Procedure for N-Unsubstituted Isoxazolidines via Nitrone-Olefin Cycloaddition. Remarkable Catalytic Effect of Bu2SnO

Abstract The remarkable catalysis of Bu2SnO for nitrone formation in the nitrone-olefin cycloaddition reaction has been discovered, and has led to the development of a general method for the synthesis of N-unsubstituted isoxazolidine derivatives.

Ring-opening of isoxazolidine nucleus: Competitive formation of α,β-enones and tetrahydro-1,3-oxazines

Treatment of isoxazolidine derivatives with methyl iodide, followed by simple heating with aqueous NaOH, gives rise to a competitive formation of α,β-enones and tetrahydro-1,3-oxazines. The ring-opening process is controlled by the stereochemistry of H 5 which represents the driving factor of two competitive reaction routes.

Optically active tricarbonyl(η6-o-trimethylsilylbenzaldehyde)chromium(O) complexes in organic synthesis: a highly diastereoselective 1,3-dipolar cycloaddition with electron-rich olefins

Heating of a racemic nitrone 2, derived from tricarbonyl(η6-o-trimethylsilylbenzaldehyde)chromium(o) complex 1, with electron-rich olefins gave after decomplexation the cis-3,5-disubstituted isooxazolidines in a highly stereo- and regio-selective manner. Similarly, high selectivities were observed when the nitrone 9 possessing no silyl group at the ortho position on its benzene ring was employed instead of 2. The corresponding non-complexed nitrones were found to provide the cis-isoxazolidines in a moderately selective fashion or the trans-ones predominantly. Treatment of chiral 2 with electron-rich olefins afforded the corresponding chiral cis-3,5-disubstituted isoxazolidines exclusively. The enantiomeric excess for cycloadducts thus obtained was determined to be 96- > 98%. The absolute configuration of these optically active isoxazolidine derivatives was established on the basis of an X-ray crystallographic analysis.

X‐Ray Structure of N‐Methyl‐3β, 5‐Epoxyimino‐5 β‐Cholest‐1‐Ene

AbstractThe molecular structure of the title compound, a steroidal isoxazolidine derivative, which is formed by transannular nitrone 1,3‐dipolar cycloaddition in the reaction of (Z)‐3β‐acetoxy‐5, 10‐secocholest‐1(10)‐en‐5‐one with N‐methylhydroxylamine, was determined by X‐ray analysis, confirming the 1(2)‐position of the double bond and the presence of a cis‐3β,5β‐epoxyimino bridge.

ChemInform Abstract: 3‐(Substituted Phenyl)‐3‐(1H‐1,2,4‐triazol‐1‐ylmethyl)‐2‐methyl‐5‐((Substituted Phenoxy)methyl)isoxazolidine Derivatives: Structure‐Activity Relationships.

ChemInformVolume 20, Issue 26 Other Subjects ChemInform Abstract: 3-(Substituted Phenyl)-3-(1H-1,2,4-triazol-1-ylmethyl)-2-methyl-5-((Substituted Phenoxy)methyl)isoxazolidine Derivatives: Structure-Activity Relationships. G. A. BENNETT, Dep. Org. Chem., Pharm. Div., Pennwalt Corp., Rochester, NY 14623, USASearch for more papers by this authorP. A. SWIFT, Dep. Org. Chem., Pharm. Div., Pennwalt Corp., Rochester, NY 14623, USASearch for more papers by this authorG. B. MULLEN, Dep. Org. Chem., Pharm. Div., Pennwalt Corp., Rochester, NY 14623, USASearch for more papers by this authorS. D. ALLEN, Dep. Org. Chem., Pharm. Div., Pennwalt Corp., Rochester, NY 14623, USASearch for more papers by this authorJ. T. MITCHELL, Dep. Org. Chem., Pharm. Div., Pennwalt Corp., Rochester, NY 14623, USASearch for more papers by this authorC. R. KINSOLVING, Dep. Org. Chem., Pharm. Div., Pennwalt Corp., Rochester, NY 14623, USASearch for more papers by this authorV. S. GEORGIEV, Dep. Org. Chem., Pharm. Div., Pennwalt Corp., Rochester, NY 14623, USASearch for more papers by this author G. A. BENNETT, Dep. Org. Chem., Pharm. Div., Pennwalt Corp., Rochester, NY 14623, USASearch for more papers by this authorP. A. SWIFT, Dep. Org. Chem., Pharm. Div., Pennwalt Corp., Rochester, NY 14623, USASearch for more papers by this authorG. B. MULLEN, Dep. Org. Chem., Pharm. Div., Pennwalt Corp., Rochester, NY 14623, USASearch for more papers by this authorS. D. ALLEN, Dep. Org. Chem., Pharm. Div., Pennwalt Corp., Rochester, NY 14623, USASearch for more papers by this authorJ. T. MITCHELL, Dep. Org. Chem., Pharm. Div., Pennwalt Corp., Rochester, NY 14623, USASearch for more papers by this authorC. R. KINSOLVING, Dep. Org. Chem., Pharm. Div., Pennwalt Corp., Rochester, NY 14623, USASearch for more papers by this authorV. S. GEORGIEV, Dep. Org. Chem., Pharm. Div., Pennwalt Corp., Rochester, NY 14623, USASearch for more papers by this author First published: June 27, 1989 https://doi.org/10.1002/chin.198926334AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume20, Issue26June 27, 1989 RelatedInformation

Selection of orally active antifungal agents from 3,5-substituted isoxazolidine derivatives based on acute efficacy-safety profiles.

Routine in vitro screening of a new synthetic series of 3,5-substituted 2-methylisoxazolidines revealed that three imidazole analogs (PR 967-248, PR 967-234, and PR 969-566) and, to a lesser extent, a triazole analog (PR 988-399) exerted rather potent antifungal activity against three systemic and four dermatophytic classes of fungi. When tested in vivo for ability to eradicate Candida vaginitis in the rat, the triazole derivative, PR 988-399, was effective after oral administration. In this in vivo test for efficacy, PR 967-234 and PR 969-566 reduced but did not eradicate the infection, while PR 967-248 was inactive. PR 988-399 was, moreover, 4- to 13-fold less potent than the three imidazoles in inhibiting testosterone synthesis in isolated rat Leydig cells. After oral or intravenous administration, PR 988-399 and PR 969-566 elicited the fewest cardiovascular and behavioural side effects in conscious dogs. The rat safety study consisted of oral dosing followed by evaluation of the exploratory motor activity of the naive animals in a novel environment. Motor activity was suppressed least by PR 988-399 and most by PR 969-566. In a battery of mouse behavioural-neuromuscular-drug interaction tests, PR 988-399 and PR 969-566 produced the fewest central-behavioural-neuromuscular signs. These efficacy-safety evaluations were performed with ketoconazole as a positive reference standard. The sequence of drug testing with respect to efficacy-safety considerations appears to be a suitable approach for early detection of orally active antifungal agents such as PR 988-399 for more advanced development.

Synthesis of isoxazolidine derivatives from N-substituted hydroxylamines and ?,?-unsaturated ketones

The reaction of methyl vinyl ketone with N-Phenyl-hydroxylamine leads to a tautomeric mixture of 5-hydroxy-2-phenyl-5-methylisoxazolidine and its linear form, while the reaction with benzohydroxamic acid leads to linear products of addition to the oxygen or nitrogen atoms, depending on the reaction conditions. The first representatives of 5-hydroxyisoxazolidines with the residue of an aliphatic carboxylic acid attached to the nitrogen atom were obtained by acylation of 5-hydroxy-3,3,5-trimethylisoxazolidine.

Studies on antifungal agents. 20. Effect of the nitrogen substitution on the in vitro activity of novel 3,5-substituted isoxazolidines.

The effect of the nitrogen substitution on the in vitro antifungal activity of a series of novel cis-3,5-substituted isoxazolidine derivatives is investigated. The 2-(N-methyl) analogues 4-6 were found to be the most active compounds when tested in vitro against Trichophyton rubrum, Aspergillus fumigatus and Candida albicans, with MIC values ranging between 0.7 and 70 micrograms/ml.