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Girija S. Singh - One of the best experts on this subject based on the ideXlab platform.
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unanticipated products from reductive and oxidative cleavages of 1 substituted 3 3 diphenyl 1 methylspiro azetidine 2 3 indoline 2 4 diones
Journal of Heterocyclic Chemistry, 2011Co-Authors: Girija S. Singh, Patrick M LunthaAbstract:Titled spiroazetidinones 1a, 1b undergo reductive cleavage on treatment with excess lithium aluminum hydride forming 3-benzhydryl-1-methylindole as the main product together with a γ-amino alcohol depending upon the substituent present on the Azetidin-2-One ring. Treatment of 1a with Ce(IV) ammonium nitrate affords 2-hydroxy-N-(4-methoxyphenyl)-2,2-diphenylacetamide besides the anticipated N-unsubstituted 2-azetidinone, whereas a similar treatment of 1-benzhydryl-3,3-diphenyl-2-azetidinone 1b affords the ring expansion product 1,3-oxazolidin-4-one. The products have been characterized on the basis of satisfactory analytical and spectral (IR, 1H and 13C-NMR, DEPT, HMBC) data and their formation is discussed. J. Heterocyclic Chem., (2011).
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Azetidines, Azetines and Azetes: Monocyclic
Comprehensive Heterocyclic Chemistry III, 2008Co-Authors: Girija S. Singh, Matthias D'hooghe, N. De KimpeAbstract:The four-membered azaheterocycles, azetidines and Azetidin-2-Ones are thermally stable and easy to handle. Structures of many compounds have been established by X-ray crystallography. Azetidines react with electrophiles and nucleophiles. The ring opening affords useful amides, alkenes, and amines. Cyclic products such as piperidines, pyrrolidines, and pyrroles have been synthesized from azetidines. Oxidation of 3-hydroxyazetidines forms azetidin-3-ones. Azetidines are synthesized from acyclic precursors like γ-haloamines, γ-aminoalcohols, and β-aminoallenes. Reactions of 1,3-dielectrophiles with primary amines and cycloadditions are also used in the synthesis of azetidines. Reduction of β-lactams affords azetidines. Heterocycles like aziridines, oxetanes, and azabicyclobutanes are transformed into azetidines. Azetidin-2-Ones (β-lactams) are precursors of β-amino acids, amides, 3,3-dichloroazetidines, and many other heterocyclic compounds. The syntheses of β-lactams involve cyclizations of β-amino acids, β-amino esters, β-functionalized amides, and cyclocondensations of isocyanates and alkenes, imines and enolates, imines and ketenes, and nitrones and alkynes. The application of chiral auxiliaries and catalysts has made considerable progress in asymmetric synthesis. Applications of microwaves and polymer supports are reported. Although β-lactams are mainly antibacterials, many compounds have been tested and shown promising results as cholesterol absorption inhibitors (CAIs), enzyme inhibitors, anticancer agents, and hypoglycemic agents. A monocyclic Azetidin-2-One (ezetimibe) is now in clinical use as CAI. Azetines and azetes comprise a rare class of constrained azaheterocycles. Only a few stable compounds belonging to these classes are known. Azetines undergo ring opening and cycloaddition reactions. Azetines are synthesized by photochemical cyclization of amides and by partial reduction of azetes. Tri-t-butylazete is a kinetically stabilized compound, which undergoes reduction, cycloaddition, and cycloreversion. It is synthesized by photolysis of pyridazines, and by thermolysis or photolysis of Dewar pyridazines.
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Azetidin-2-One versus chroman-2-one: Application of 1H- 13C COSY NMR and mass spectroscopy in structure elucidation-class of compounds
Spectroscopy Letters, 2008Co-Authors: Girija S. Singh, Tshepo PhekoAbstract:Abstract Azetidin‐2‐ones, commonly known as β‐lactams, constitute a biologically important class of compound. Treatment of azetidin‐2‐ones with alkali is known to form diverse types of compounds depending on the stability of the ring. In many cases, the ring is retained in the product at the cost of transformation of substituents. Spectroscopy is the most important tool to characterize the organic compounds. However, in some cases the structures of the products are so closely related that simple IR, 1H NMR, and 13C NMR spectra do not lead to unambiguous structure elucidation. This article reports a novel application of 1H‐13C COSY NMR and mass spectroscopy in determining unequivocally an azetidin‐2‐one ring structure instead of a chroman‐2‐one ring structure for the product obtained by treatment of 1‐benzhydryl‐3,3‐bis(4‐methylphenyl)‐4‐[2‐(o‐dip‐tolylacyl)hydroxyphenyl]‐2‐azetidinone with ethanolic sodium hydroxide at room temperature.
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Spectroscopic characterization of the 1-substituted 3,3-diphenyl-4-(2′-hydroxyphenyl)Azetidin-2-Ones: Application of 13C NMR, 1H–13C COSY NMR and mass spectroscopy
Spectrochimica acta. Part A Molecular and biomolecular spectroscopy, 2007Co-Authors: Girija S. Singh, Tshepo PhekoAbstract:Abstract The article deals with spectroscopic characterization of Azetidin-2-Ones. The presence of substituents like hydroxyl, fluoro, methoxy and benzhydryl, etc., on the Azetidin-2-One ring significantly affects the IR absorption and 13 C NMR frequencies of the carbonyl group present in these compounds. The presence of an ester carbonyl group or too many methine protons in the molecule has been observed to limit the scope of IR and 1 H NMR spectroscopy in unambiguous assignment of the structure. The application of 13 C NMR, 2D NMR ( 1 H– 13 C COSY) and mass spectroscopy in characterization of complex Azetidin-2-Ones is discussed. An application of the latter two techniques is described in deciding unequivocally between an Azetidin-2-One ring and chroman-2-one ring structure for the product obtained by treatment of the 1-substituted 3,3-diphenyl-4-[2′-( O -diphenylacyl)hydroxyphenyl]-2-azetidinones with ethanolic sodium hydroxide at room temperature.
Tshepo Pheko - One of the best experts on this subject based on the ideXlab platform.
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Azetidin-2-One versus chroman-2-one: Application of 1H- 13C COSY NMR and mass spectroscopy in structure elucidation-class of compounds
Spectroscopy Letters, 2008Co-Authors: Girija S. Singh, Tshepo PhekoAbstract:Abstract Azetidin‐2‐ones, commonly known as β‐lactams, constitute a biologically important class of compound. Treatment of azetidin‐2‐ones with alkali is known to form diverse types of compounds depending on the stability of the ring. In many cases, the ring is retained in the product at the cost of transformation of substituents. Spectroscopy is the most important tool to characterize the organic compounds. However, in some cases the structures of the products are so closely related that simple IR, 1H NMR, and 13C NMR spectra do not lead to unambiguous structure elucidation. This article reports a novel application of 1H‐13C COSY NMR and mass spectroscopy in determining unequivocally an azetidin‐2‐one ring structure instead of a chroman‐2‐one ring structure for the product obtained by treatment of 1‐benzhydryl‐3,3‐bis(4‐methylphenyl)‐4‐[2‐(o‐dip‐tolylacyl)hydroxyphenyl]‐2‐azetidinone with ethanolic sodium hydroxide at room temperature.
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Spectroscopic characterization of the 1-substituted 3,3-diphenyl-4-(2′-hydroxyphenyl)Azetidin-2-Ones: Application of 13C NMR, 1H–13C COSY NMR and mass spectroscopy
Spectrochimica acta. Part A Molecular and biomolecular spectroscopy, 2007Co-Authors: Girija S. Singh, Tshepo PhekoAbstract:Abstract The article deals with spectroscopic characterization of Azetidin-2-Ones. The presence of substituents like hydroxyl, fluoro, methoxy and benzhydryl, etc., on the Azetidin-2-One ring significantly affects the IR absorption and 13 C NMR frequencies of the carbonyl group present in these compounds. The presence of an ester carbonyl group or too many methine protons in the molecule has been observed to limit the scope of IR and 1 H NMR spectroscopy in unambiguous assignment of the structure. The application of 13 C NMR, 2D NMR ( 1 H– 13 C COSY) and mass spectroscopy in characterization of complex Azetidin-2-Ones is discussed. An application of the latter two techniques is described in deciding unequivocally between an Azetidin-2-One ring and chroman-2-one ring structure for the product obtained by treatment of the 1-substituted 3,3-diphenyl-4-[2′-( O -diphenylacyl)hydroxyphenyl]-2-azetidinones with ethanolic sodium hydroxide at room temperature.
Mary J. Meegan - One of the best experts on this subject based on the ideXlab platform.
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Azetidin-2-Ones: structures of anti-mitotic compounds based on the 1-(3,4,5-tri-meth-oxy-phen-yl)Azetidin-2-One core.
Acta crystallographica. Section E Crystallographic communications, 2020Co-Authors: Brendan Twamley, Niamh M O'boyle, Mary J. MeeganAbstract:A series of related substituted 1-(3,4,5-tri-meth-oxy-phen-yl)Azetidin-2-Ones have been characterized: 3-(4-fluoro-phen-yl)-4-(4-meth-oxy-phen-yl)-1-(3,4,5-tri-meth-oxy-phen-yl)Azetidin-2-One, C25H24FNO5 (1), 3-(furan-2-yl)-4-(4-meth-oxy-phen-yl)-1-(3,4,5-tri-meth-oxy-phen-yl)Azetidin-2-One, C23H23NO6 (2), 4-(4-meth-oxyphen-yl)-3-(naphthalen-1-yl)-1-(3,4,5-tri-meth-oxy-phen-yl)Azetidin-2-One, C29H27NO5 (3), 3-(3,4-di-meth-oxy-phen-yl)-4-(4-meth-oxy-phen-yl)-1-(3,4,5-tri-meth-oxy-phen-yl)Azetidin-2-One, C27H29NO7 (4) and 4,4-bis-(4-meth-oxy-phen-yl)-3-phenyl-1-(3,4,5-tri-meth-oxy-phen-yl)Azetidin-2-One, C32H31NO6 (5). All of the compounds are racemic. The lactam and 3,4,5-tri-meth-oxy-phenyl rings are approximately co-planar and the orientation of the lactam and the 4-meth-oxy-phenyl substituent is approximately orthogonal. The chiral centres, although eclipsed by geometry, have torsion angles ranging from -7.27 to 13.08° for the 3 position, and -8.69 to 13.76° for the 4 position of the β-lactam. The structures display intra-molecular C-H⋯O bonding between the 3,4,5-tri-meth-oxy-phenyl ring and the lactam ketone. Further C-H⋯O inter-actions are observed and form either an opposing meth-oxy 'buckle' to join two mol-ecules together or a cyclic dimer.
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Transformation of 4-Acetoxy-3-VinylAzetidin-2-Ones to 3-(1-Hydroxyethyl)Azetidin-2-Ones and 3-EthylideneAzetidin-2-Ones: Intermediates for Carbapenem Antibiotics
Journal of Chemical Research, 2001Co-Authors: Anthony D. Neary, Aisling C. O'leary, Catherine M. Burke, Mary J. MeeganAbstract:4-Acetoxy-3-vinylAzetidin-2-One and 4-formyl-3-vinylAzetidin-2-One are transformed to the carbapenem intermediates 4-acetoxy-3-(1-hydroxyethyl)Azetidin-2-One and 4-acetoxy-3-ethylideneAzetidin-2-One respectively, and the synthesis of a 6-vinylcarbapenem is reported.
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3-(2-Alkoxy-1-hydroxyethyl)Azetidin-2-Ones: Potential Intermediates for the Synthesis of Novel Carbapenems
Journal of Chemical Research, 1998Co-Authors: Aisling C. O'leary, C. M. Waldron, Catherine M. Burke, Raymond D. Keaveny, Mary J. MeeganAbstract:3-Vinyl and 3-isopropenylAzetidin-2-Ones can be transformed into the corresponding 3-(2-alkoxy-1-hydroxyethyl)Azetidin-2-Ones and 3-(1-alkoxy-2-hydroxypropan-2-yl)Azetidin-2-Ones by regioselective alcoholysis of 3-(1,2-epoxyethyl)Azetidin-2-Ones; 4-acetoxy-3-(1-hydroxy-2-methoxyethyl)-1-(4-methoxyphenyl)Azetidin-2-One 14 is a synthetic precursor for carbapenems having both alcohol and alkoxyalcohol substituents at C-8.
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4-Acetoxy-3-[1-(2-arylamino-1-hydroxy)ethyl]Azetidin-2-One s: Intermediates for the Synthesis of Novel Carbapenems
Journal of Chemical Research, 1997Co-Authors: Mary J. Meegan, C. M. Waldron, Raymond D. Keaveny, Anthony D. NearyAbstract:3-Vinyl- and 3-isopropenyl-Azetidin-2-Ones are transformed into the corresponding 4-acetoxy-3-[1-(2-arylamino-1-hydroxy)ethyl]Azetidin-2-Ones and 4-acetoxy-3-[1-(2-arylamino-1-hydroxy)propyl]Azetidin-2-Ones, intermediates for the synthesis of novel carbapenems.
Matthias D'hooghe - One of the best experts on this subject based on the ideXlab platform.
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Use of 3-Hydroxy-4-(trifluoromethyl)Azetidin-2-Ones as Building Blocks for the Preparation of Trifluoromethyl-Containing Aminopropanes, 1,3-Oxazinan-2-ones, Aziridines, and 1,4-Dioxan-2-ones
Synthesis, 2018Co-Authors: Hang Dao Thi, Giang Le Nhat Thuy, Saron Catak, Veronique Van Speybroeck, Tuyen Van Nguyen, Matthias D'hoogheAbstract:3-Hydroxy-4-(trifluoromethyl)Azetidin-2-Ones were synthesized from the corresponding 3-benzyloxy-β-lactams and successfully transformed into new 3-chloro-4-(trifluoromethyl)Azetidin-2-One building blocks. The latter chlorides were shown to be eligible precursors for the construction of CF 3 -containing aminopropanes, 1,3-oxazinanes, 1,3-oxazinan-2-ones, and aziridines. In addition, 3-hydroxy-4-(trifluoromethyl)Azetidin-2-Ones proved to be interesting substrates for the synthesis of novel 3-[2,2,2-trifluoro-1-(arylamino)ethyl]-1,4-dioxan-2-ones via intramolecular cyclization of 3-(2-hydroxyethoxy)-β-lactam intermediates.
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Synthesis and reactivity of 4-(trifluoromethyl)Azetidin-2-Ones
Monatshefte für Chemie - Chemical Monthly, 2018Co-Authors: Hang Dao Thi, Tuyen Van Nguyen, Matthias D'hoogheAbstract:Because of the beneficial effect of a trifluoromethyl group on the biological properties of bioactive compounds on the one hand and the versatile synthetic potential of beta-lactams on the other hand, 4-CF3-beta-lactams comprises interesting entities for the preparation of a large variety of CF3-substituted nitrogen-containing target structures with promising biological characteristics. In this review, we present an overview of different building block approach-based routes toward the synthesis of 4-(trifluoromethyl)Azetidin-2-Ones and the application of the "beta-lactam synthon method" for the synthesis of a diverse set of (a)cyclic CF3-substituted molecules by means of ring-opening and ring-transformation reactions.
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Azetidines, Azetines and Azetes: Monocyclic
Comprehensive Heterocyclic Chemistry III, 2008Co-Authors: Girija S. Singh, Matthias D'hooghe, N. De KimpeAbstract:The four-membered azaheterocycles, azetidines and Azetidin-2-Ones are thermally stable and easy to handle. Structures of many compounds have been established by X-ray crystallography. Azetidines react with electrophiles and nucleophiles. The ring opening affords useful amides, alkenes, and amines. Cyclic products such as piperidines, pyrrolidines, and pyrroles have been synthesized from azetidines. Oxidation of 3-hydroxyazetidines forms azetidin-3-ones. Azetidines are synthesized from acyclic precursors like γ-haloamines, γ-aminoalcohols, and β-aminoallenes. Reactions of 1,3-dielectrophiles with primary amines and cycloadditions are also used in the synthesis of azetidines. Reduction of β-lactams affords azetidines. Heterocycles like aziridines, oxetanes, and azabicyclobutanes are transformed into azetidines. Azetidin-2-Ones (β-lactams) are precursors of β-amino acids, amides, 3,3-dichloroazetidines, and many other heterocyclic compounds. The syntheses of β-lactams involve cyclizations of β-amino acids, β-amino esters, β-functionalized amides, and cyclocondensations of isocyanates and alkenes, imines and enolates, imines and ketenes, and nitrones and alkynes. The application of chiral auxiliaries and catalysts has made considerable progress in asymmetric synthesis. Applications of microwaves and polymer supports are reported. Although β-lactams are mainly antibacterials, many compounds have been tested and shown promising results as cholesterol absorption inhibitors (CAIs), enzyme inhibitors, anticancer agents, and hypoglycemic agents. A monocyclic Azetidin-2-One (ezetimibe) is now in clinical use as CAI. Azetines and azetes comprise a rare class of constrained azaheterocycles. Only a few stable compounds belonging to these classes are known. Azetines undergo ring opening and cycloaddition reactions. Azetines are synthesized by photochemical cyclization of amides and by partial reduction of azetes. Tri-t-butylazete is a kinetically stabilized compound, which undergoes reduction, cycloaddition, and cycloreversion. It is synthesized by photolysis of pyridazines, and by thermolysis or photolysis of Dewar pyridazines.
Jacqueline Marchand-brynaert - One of the best experts on this subject based on the ideXlab platform.
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(S)-1-(Pent-4’-enoyl)-4-(hydroxymethyl)-Azetidin-2-One derivatives as inhibitors of human fatty acid amide hydrolase (hFAAH): synthesis, biological evaluation and molecular modelling
Journal of enzyme inhibition and medicinal chemistry, 2013Co-Authors: Joséphine Caruano, Marion Feledziak, Geoffray Labar, Catherine Michaux, Eric A. Perpète, Giulio G. Muccioli, Raphaël Robiette, Jacqueline Marchand-brynaertAbstract:A series of lipophilic ester derivatives (2a-g) of (S)-1-(pent-4’-enoyl)-4-(hydroxymethyl)-Azetidin-2-One has been synthesized in three steps from (S)-4-(benzyloxycarbonyl)-Azetidin-2-One and evaluated as novel, reversible, ?-lactamic inhibitors of endocannabinoid-degrading enzymes (hFAAH and hMAGL). The compounds showed IC50 values in the micromolar range and selectivity for hFAAH versus hMAGL. The unexpected thousandfold decrease of activity of 2a comparatively to the known regioisomeric structure 1a (i.e. lipophilic chains placed on N1 and C3 positions of the ?-lactam core) could be explained on the basis of docking studies into a revisited model of hFAAH active site, considering one or two water molecules in interaction with the catalytic triad.
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Synthesis of (1′R,3S,4S)‐3‐[1′‐(tert‐Butyldimethylsilyloxy)ethyl]‐ 4‐(cyclopropylcarbonyloxy)azetidin‐2‐one
European Journal of Organic Chemistry, 2006Co-Authors: Mathieu Laurent, Marcel Cérésiat, Jacqueline Marchand-brynaertAbstract:The novel carbapenem precursor 1e has been synthesized from L-threonine, cyclopropyl methyl ketone and benzhydrylamine (for the introduction of the azetidinone N-protecting group). Two independently prepared building blocks sodium (2R,3R)-2,3-epoxybutyrate as a mixed salt with NaBr (2b) and N-(benzhydryl)aminomethyl cyclopropyl ketone (4e) - were coupled to give (2R,3R)-N-(benzhydryl)-N-(2-cyclopropyl-2-oxoethyl)-2,3-epoxybutyramide (Be). This key intermediate gave a regio- and stereoselective C3-C4 ring closure on LiHMDS treatment in THF at 0 degrees C to yield (1'R,3S,4S)-4-cyclopropylcarbonyl-1-diphenylmethyl-3-(1-hydroxyethyl) Azetidin-2-One (13e). N-Deprotection of 13e was performed by photochemical bromination and subsequent hydrolysis. The resulting (1'R,3S,4S)-4-(cyclopropylcarbonyl)-3-(1-hydroxyethyl) Azetidin-2-One (23e) reacted in a Baeyer-Villiger oxidation with a total control of the regioselectivity (due to the poor migratory aptitude of the cyclopropyl group) to furnish (1'R,3S,4S)-3-(1-hydroxyethyl)-4(cyclopropylcarbonyloxy) Azetidin-2-One (24e), subsequent O-silylation achieving the total synthesis of le (title compound). ((c) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)
