Isoxazolidine Derivatives Research Articles

ChemInform Abstract: Synthesis of Isomeric 2,3,5‐Trisubstituted Perhydropyrrolo[3,4‐d]isoxazole‐4,6‐diones via 1,3‐Dipolar Cycloaddition Reactions.

AbstractCycloaddition of nitrones (I) to maleimides (II) produces a diastereomeric couple of a new type of isoxazolidine derivatives.

ChemInform Abstract: A Green Approach in Aqueous Phase Synthesis of Isoxazolidine Derivatives from N‐Phenyl‐α‐amino Nitrone and Their Antibacterial Activities.

AbstractThe cycloaddition reaction affords the target compounds in excellent yields.

The Molecular Structure of the Steroidal Isoxazolidine Products Derived from (Z)-3β,17β-Diacetoxy-19-NOR-5,10-Secoandrost-1(10)-En-5-One

X-Ray analysis of the steroidal isoxazolidine derivatives 2 and 3b, which are formed (the latter as the corresponding diacetate 3a) in the reaction of (Z)-3beta, 17beta-diacetoxy-19-nor-5,10-secoandrost-l(lo)-en-5-one (1) with N-methylhydroxylamine, has revealed that both compounds (and therefore also 3a) have the same cis-1beta,5beta-epoxyimino bridge structure. The conformations of the two molecular skeletons are compared.

ChemInform Abstract: α‐N‐Methyl/Phenyl Furan Derivatives as Dipolarophiles for Synthesis of Spiro Isoxazolidine Derivatives with α‐Chloro and Simple Nitrones.

1,3-Dipolar cycloaddition reactions of α-chloro and simple nitrones have been studied with novel α-N-methyl/phenyl furan derivatives as new dipolarophiles. The reactions are found to be highly regioselective to afford single 5-spiro isoxazolidines with high yield in a short reaction time.

ChemInform Abstract: Synthesis and Antibacterial Activities of Some Novel Isoxazolidine Derivatives Derived from N‐Phenyl‐α‐chloro Nitrone in Water.

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.

α-N-Methyl/Phenyl Furan Derivatives as Dipolarophiles for Synthesis of Spiro Isoxazolidine Derivatives with α-Chloro and Simple Nitrones

1,3-Dipolar cycloaddition reactions of α-chloro and simple nitrones have been studied with novel α-N-methyl/phenyl furan derivatives as new dipolarophiles. The reactions are found to be highly regioselective to afford single 5-spiro isoxazolidines with high yield in a short reaction time.

Intramolecular approach to some new D-ring-fused steroidal isoxazolidines by 1,3-dipolar cycloaddition: synthesis, theoretical and in vitro pharmacological studies

Intramolecular 1,3-dipolar cycloaddition of alkenyl oxime 5, obtained from trans-3β-acetoxy-16,17-secopregna-5,17(20)-dien-16-al 2 with hydroxylamine hydrochloride, was carried out under reflux in toluene to furnish a ca. 3 : 2 mixture of D-ring-fused isoxazolidine diastereomers 8 and 11a both with cis D/E ring junction stereochemistry. The corresponding reaction of 5 in the presence of a catalytic amount of BF3·OEt2 gave a single isomer 8 under milder conditions with an improved yield. The experimental findings on the thermally induced and BF3-catalysed transformations were supported by calculations of the proposed mechanism at the BLYP/6-31G(d) level of theory. Analogously, cyclization of D-secopregnene aldehyde 2 with N-substituted hydroxylamine derivatives (10b–e) under thermal conditions furnished N-functionalized isoxazolidines 11b–e diastereoselectively, via the corresponding alkenyl nitrones 7b–e. The activities of the 3-deacetylated compounds (9, 12b–e) were tested in vitro on rat testicular C17,20-lyase: the radioligand incubation assay revealed that 9 exerted a moderate enzyme-inhibitory effect (IC50 = 26 μM), while the other derivatives were found to decrease the enzyme activity by only 68–83%. The antiproliferative activities of the structurally related isoxazolidine derivatives were also determined in vitro on three malignant human cell lines (HeLa, MCF7, and A431) by the microculture tetrazolium assay. The highest cytotoxic activities were displayed by the N-benzyl-substituted derivative 12e (IC50: 14.00, 23.18 and 8.76 μM on HeLa, MCF7 and A341 cells, respectively).

Antibacterial Activity, Quantitative Structure–Activity Relationship and Diastereoselective Synthesis of Isoxazolidine Derivatives Via 1,3‐Dipolar Cycloaddition of d‐glucose Derived Nitrone with Olefin

The diastereoselectivity of the intermolecular 1,3-dipolar cycloaddition reaction of d-glucose-derived nitrones with both cyclic and acyclic dipolarophiles were studied. The reaction of nitrone with acyclic dipolarophiles resulted in the formation of the endo adduct exclusively whereas with cyclic dipolarophiles endo adduct was obtained as the major product. Antibacterial activity was evaluated for these eighteen isoxazolidine derivatives against Staphylococcus aureus NCIM5021, Escherichia coli NCIM 2931 and Pseudomonas aeruginosa NCIM 5029 by twofold dilution technique using resazurin as the indicator dye. Quantitative structureactivity relationships were developed with fourteen and the model was validated with four data. Electronic and spatial descriptors were the major contributors in all the three quantitative structureactivity relationship equations and the statistical parameters r(2), r(2)(adj) , F-ratio and q(2) were found to be satisfactory.

Asymmetric reduction of racemic 2-isoxazolines

Abstract The kinetic resolution of racemic 2-isoxazolines was carried out by asymmetric reduction using borane with 1,2-amino alcohols as a chiral source. Using excess BH 3 –THF in the presence of (−)-norephedrine, optically active 1,3-amino alcohol derivatives were obtained with good ee but in lower yield, while the optically active substrates 2-isoxazolines were recovered with modest ee. The asymmetric reduction using 2.0 equiv of BH 3 –SMe 2 was investigated as an alternative strategy for the synthesis of optically active products. After reduction, treatment of the resulting mixture with Et 3 N was successful in providing optically active isoxazolidine derivatives in good yields and with good ee. The choice of chiral source was also shown to have a significant effect. In particular, the use of ( S )-α,α-diphenyl-2-pyrrolidinemethanol reversed the enantioselectivity of the recovered substrates.

ChemInform Abstract: Regio‐ and Stereoselective Synthesis of Isoxazolidine Derivatives by Asymmetric 1,3‐Dipolar Cycloaddition Reaction of Chiral Nitrones with 1‐Propene‐1,3‐sultone.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 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.

Regio‐ and stereoselective synthesis of isoxazolidine derivatives by asymmetric 1,3‐dipolar cycloaddition reaction of chiral nitrones with 1‐propene‐1,3‐sultone

Abstractmagnified imageAsymmetric 1,3‐dipolar cycloadditions of chiral nitrones to 1‐propene‐1,3‐sultone (1) were investigated. Chiral nitrones 6a‐e reacted with sultone 1 in toluene at 90 °C for 24‐36 h to give the corresponding isoxazolidines in moderate yields with high regioselectivities and stereoselectivities. The diastereoselectivity of this reaction varied with the choice of dipolarophile and the steric demands of nitrones. When sultone 1 was allowed to react chiral nitrone 6e, a much better diastereoselectivity of up to 5.1:1 was observed.

Synthesis of α-Trifluoromethyl-β-lactams and Esters of β-Amino Acids via 1,3-Dipolar Cycloaddition of Nitrones to Fluoroalkenes

Nitrones derived from aromatic or aliphatic aldehydes or ketones react with hexafluoropropene (HFP) or 2H-pentafluoropropene (PFP) to give the respective fluorinated isoxazolidine derivatives in good yields with complete regioselectivity and moderate diastereoselectivity. Catalytic hydrogenolysis of the N-O bond under ambient pressure and temperature leads to fluorides of beta-amino acids that undergo cyclization to alpha-trifluoromethylated beta-lactams or, under acidic conditions, form esters of alpha-trifluoromethylated beta-amino acids.

Novel 1,3-dipolar cycloaddition reactions of calix[4]bis(spirodienones): synthesis of isoxazolidine derived macrocycles

Calix[4]bis(spirodienones) can perform as either 4π or 2π components in cycloaddition reactions with various carbo- and hetero-dienophiles and with 1,2-benzoquinones leading to the formation of highly functionalized macrocycles. In this Letter we report, highly regio- and stereoselective 1,3-dipolar cycloaddition reactions of a bis(spirodienone) derivative of calix[4]arene with nitrones that provide easy access to isoxazolidine derived macrocycles in excellent yields. These isoxazolidine derivatives can be considered as direct precursors of 1,3-amino alcohols.

Hydrophobic-tailed bicycloisoxazolidines: A comparative study of the newly synthesized compounds on the inhibition of mild steel corrosion in hydrochloric and sulfuric acid media

The cycloaddition reactions of the cyclic nitrones 1-pyrroline 1-oxide and 3,4,5,6-tetrahydropyridine 1-oxide with alkenes, 11-phenoxy-1-undecene and 11- p-methoxyphenoxy-1-undecene, afforded cycloaddition products (bicyclic isoxazolidines) in excellent yields. One of the cycloadducts on reaction with propargyl chloride and ring opening with zinc in acetic acid afforded quaternary ammonium salt and aminoalcohol, respectively. All the new inhibitor molecules in the presence of 400 ppm at 60 °C achieved inhibition efficiencies, determined by gravimetric method, in the range 99–99.6% and 85–99% for mild steel in 1 M HCl and 0.5 M H 2SO 4, respectively. Comparable results were obtained by the electrochemical methods using Tafel plots and electrochemical impedance spectroscopy for the synthesized compounds. The isoxazolidine derivatives were also found to be good inhibitors of mold steel corrosion in synthetic brine. Negative values of Δ G ads ∘ in the acidic media ensured the spontaneity of the adsorption process. While the corrosion inhibition by these molecules was predominantly under cathodic control in 1 M HCl, the inhibition in 0.5 M H 2SO 4 was found to be under anodic control. The isoxazolidines and their derivatives were found to be among a rare class of molecules, which provide suitable inhibition mechanism for the corrosion inhibition in HCl as well as in H 2SO 4 media.

1,3‐dipolar cycloadditions. Part XII ‐ selective cycloaddition route to 4‐nitroisoxazolidine ring systems

Abstractmagnified imageCycloadditions of C,N‐diarylnitrones to β‐nitrostyrenes occurred to yield two diastereoisomeric cycloadducts, the 3,4‐trans‐4,5‐trans substituted isoxazolidine derivatives being formed selectively as the major products. These were characterised by spectroscopic and X‐ray data. Conformational studies were carried out by X‐ray crystallography and Molecular Modelling.

Efficient synthesis of 2,6,7,8-tetrahydroxyindolizidines (castanospermine analogues) via the dipolar cycloadditions of N-benzyl- C-(tetrofuranos-4-yl)nitrones to methyl acrylate

The dipolar cycloaddition of ( Z)- N-benzyl-(3- O-benzyl-1,2- O-isopropylidene-α- d-ribofuranos-5-ylidene)amine N-oxide to methyl acrylate gives a 53:16:26:5 diastereomeric mixture of isoxazolidine derivatives. The dipolar cycloaddition of the xylo analogue to methyl acrylate is more diastereoselective, producing a 44:13:43 mixture of only three diastereomers. The ribo-configured adducts have been converted (4 steps only) into the new (2 R,6 S,7 S,8 R,8a R)-, (2 S,6 S,7 S,8 R,8a R)-, (2 S,6 S,7 S,8 R,8a S)- and (2 R,6 S,7 S,8 R,8a S)-2,6,7,8-tetrahydroxyindolizidines. Similarly, the two xylo-configured major isoxazolidine derivatives were converted into the known derivatives (2 R,6 S,7 R,8 R,8a S)- and (2 S,6 S,7 R,8 R,8a R)-2,6,7,8-tetrahydroxyindolizidines. The six isomeric indolizidine derivatives obtained have been evaluated for their inhibiting activities towards 15 glycosidases. Only the (2 R,6 S,7 S,8 R,8a R)-configured isomer is a selective inhibitor of amyloglucosidases from Aspergillus niger (IC 50 = 350 μM) and from Rhizopus mold (IC 50 = 90 μM, K i = 195 μM, non-competitive), the other indolizidines show very little inhibitory activity at 1 mM concentration.

An Efficient and Diastereoselective Intramolecular 1,3‐Dipolar Cycloaddition of Cyclic Azomethine Ylides and Nitrones.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Palladium(0)‐Catalyzed Cascade One‐Pot Synthesis of Isoxazolidines.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Palladium(0)-catalyzed cascade one-pot synthesis of isoxazolidines

A highly diastereoselective cascade reaction protocol has been developed for the synthesis of isoxazolidine derivatives utilizing aryl halides, O-homoallyl hydroxylamine and palladium(0) in a one-pot reaction.

A short and highly stereoselective route to polyhydroxy-perhydroazaazulenes via a C-( d- galacto-pentopyranos-5-yl)isoxazolidine

A short and efficient route to enantiomerically pure hexahydroxy- and pentahydroxy-perhydroazaazulenes, ring-homologues of castanospermine, starting from the sole isoxazolidine derivative obtained in the 1,3-dipolar cycloaddition of a d-galactose-derived nitrone and methyl acrylate, is established. The procedure allows both backbone and stereochemical modulation of the products by choice of the starting monosaccharide. Structural assignment was based on crystallographic analysis of the starting isoxazolidine and NMR techniques. The products were tested for inhibitory activity against several glycosidases.