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Steven D. Bull - One of the best experts on this subject based on the ideXlab platform.
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Solid-phase asymmetric synthesis using a polymer-supported chiral Evans'-type Oxazolidin-2-One
Nature Protocols, 2013Co-Authors: Rachel Green, Jennifer Peed, James E Taylor, Richard A R Blackburn, Steven D. BullAbstract:This protocol describes the synthesis of ( S )-4-(4-hydroxybenzyl)-Oxazolidin-2-One, its attachment to a Merrifield-Cl resin and its use for asymmetric synthesis. The chiral auxiliary is prepared in four steps from N -Boc- L -tyrosine on a multigram scale in high yield and attached to Merrifield-Cl resin via its phenolic group to afford a solid-supported chiral auxiliary for asymmetric synthesis that takes ∼7 d to prepare. A procedure for its N -acylation is reported and a method for carrying out diastereoselective solid-supported Evans' syn -aldol reactions is described, with aldol products being cleaved from the polymer by either hydrolysis or reduction. The use of the supported auxiliary for two sequential 'on-bead' reactions has been demonstrated for the synthesis of a chiral cyclopropane aldol and a γ-lactone in a >95:5 diastereomeric ratio. These polymer-supported reactions are carried out in IRORI Kan resin capsules to protect the polymer support from mechanical degradation, thus allowing multiple on-bead reactions to be performed.
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A cleavable linker strategy for optimising enolate alkylation reactions of a polymer-supported Evans' Oxazolidin-2-One
Chemical Communications, 2007Co-Authors: Rachel Green, Andrew Merritt, Steven D. BullAbstract:A cleavable linker strategy has been used to optimise the enolate alkylation reactions of a recyclable L-tyrosine derived polymer-supported Oxazolidin-2-One for the asymmetric synthesis of a series of chiral α-alkyl acids.
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A practical synthesis of enantiopure (S)-4-(4-hydroxybenzyl)-Oxazolidin-2-One
Tetrahedron-asymmetry, 2003Co-Authors: Rachel Green, Piers J.m. Taylor, Steven D. Bull, Tony D. James, Mary F. Mahon, Andy MerrittAbstract:A high yielding four-step synthesis of enantiopure 4-(4-hydroxybenzyl)-Oxazolidin-2-One (S)-1 from N-Boc-L-tyrosine is described. (S)-1 is a key intermediate for the preparation of a number of polymer supported Evans' Oxazolidin-2-Ones that have been employed previously for solid supported asymmetric synthesis. (C) 2003 Elsevier Ltd. All rights reserved.
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Rearrangements and racemisation during the synthesis of l-serine derived Oxazolidin-2-Ones
Tetrahedron, 2002Co-Authors: Steven D. Bull, Stephen G. Davies, Edward D. Savory, David J. WatkinAbstract:Abstract The propensity for N-Boc-4-hydroxymethyl-Oxazolidin-2-Ones to undergo rapid O–O and N–O carbonyl transfer makes these l -serine derived chiral auxiliaries unsuitable for attachment to polymers.
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Polymer supported Oxazolidin-2-Ones derived from l-serine—a cautionary tale
Tetrahedron Letters, 2000Co-Authors: Steven D. Bull, Stephen G. DaviesAbstract:The capacity of N-Boc-4-hydroxymethyl-Oxazolidin-2-Ones to undergo rapid O-O and N-O acyl transfer makes these serine derived chiral auxiliaries unsuitable for attachment to polymers. (C) 2000 Elsevier Science Ltd.
Ganapati D Yadav - One of the best experts on this subject based on the ideXlab platform.
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K–La–MgO as heterogeneous catalyst for synthesis of 3-(2-hydroxyethyl)-1,3-Oxazolidin-2-One from diethanol amine and carbon dioxide
Clean Technologies and Environmental Policy, 2018Co-Authors: Pooja R. Tambe, Ganapati D YadavAbstract:Cost-effective valorization of carbon dioxide into bulk and specialty chemicals using catalysis will be attractive in the foreseeable future. 1,3-Oxazolidin-2-One derivatives are one of the important classes of heterocyclic compounds which have wide applications in pharmaceutical industries due to their biological activities such as antibacterial, antimicrobial, antiseptic. Various synthetic routes are employed to prepare these compounds which include phosgenation, oxidative carbonylation, etc., which make use of polluting chemicals and homogeneous catalysts. The heterogeneous catalytic processes to synthesize these derivatives are quite limited. Thus, developing a green route which is environmental friendly is highly desirable. The current work deals with development of a heterogeneous reusable catalyst and its application to synthesize 1,3-Oxazolidin-2-One derivatives using carbon dioxide as a C1 source. The fact that no use of promoter or organic co-catalyst is made in the current process makes the synthesis route more favorable. Pure La–MgO and K–La–MgO with different K loading (1, 3, 5, and 7 wt%) synthesized by combustion route were screened for carbonylation of diethanol amine. 5% K–La–MgO was found to be the best catalyst. The catalyst was well characterized in virgin form and after use by various analytical techniques like TEM, SEM, XRD, CO_2 and NH_3-TPD, BET surface area analysis. With 5% K–La/MgO, 72% conversion of diethanol amine was achieved with 100% selectivity of the desired product at optimum conditions, i.e., 150 °C, 5 wt% K–La/MgO catalyst loading of 0.02 g/cm^3 and 2.0 MPa CO_2 pressure. Reaction mechanism was proposed and kinetic model developed. The apparent activation energy was calculated as 18.76 kcal/mol. The catalyst was robust and recyclable. The process is clean and green.
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novelty of immobilized enzymatic synthesis of 3 ethyl 1 3 oxazolidin 2 one using 2 aminoalcohol and dimethyl carbonate mechanism and kinetic modeling of consecutive reactions
Journal of Molecular Catalysis B-enzymatic, 2014Co-Authors: Ganapati D Yadav, Sandip V PawarAbstract:Abstract Oxazolidinones are multifunctional compounds possessing diverse biological and pharmacological activity. Enzymatic synthesis of Oxazolidin-2-One was studied using 2-aminoalochol and dimethyl carbonate and synthesis of 3-ethyl-1,3-Oxazolidin-2-One was chosen as the model reaction using a variety of immobilized lipases; among which Candida antarctica lipase B (Novozyme 435) was the best catalyst. The reaction leads to the final product Oxazolidin-2-One via methyl ethyl (2-hydroxyethyl) carbamate as the intermediate. The parameters affecting rate of reaction and the conversion of both steps were studied systematically and covered effects of agitation speed, solvent, catalyst loading and reaction temperature. A reaction mechanism was proposed wherein the coproduct methanol is generated in the first step leading to the formation of methyl ethyl (2-hydroxyethyl) carbamate as the intermediate which rearranges itself leading to the final products 3-ethyl-1,3-Oxazolidin-2-One and methanol. The kinetic constant and activation energy were determined for each step of the reaction. The study was further extended to other 2-aminoalochols under optimized reaction conditions to prepare different oxazolidinones. This is a first report of its kind describing kinetics and mechanism of bimolecular consecutive enzyme catalyzed reactions.
Eric J. Thomas - One of the best experts on this subject based on the ideXlab platform.
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Stereoselective synthesis of oxazolidinonyl-fused piperidines of interest as selective muscarinic (M1) receptor agonists: a novel M1 allosteric modulator
Organic and Biomolecular Chemistry, 2016Co-Authors: Kenneth J. Broadley, Maxime G. P. Buffat, Robin H. Davies, Erica S. Burnell, Xavier Moreau, Stephen Snee, Eric J. ThomasAbstract:Syntheses of (1RS,2SR,6SR)-2-alkoxymethyl-, 2-hetaryl-, and 2-(hetarylmethyl)-7-arylmethyl-4,7-diaza-9-oxabicyclo[4.3.0]nonan-8-ones, of interest as potential muscarinic M1 receptor agonists, are described. A key step in the synthesis of (1RS,2SR,6SR)-7-benzyl-6-cyclobutyl-2-methoxymethyl-4,7-diaza-9-oxabicyclo[4.3.0]nonan-8-one, was the addition of isopropenylmagnesium bromide to 2-benzyloxycarbonylamino-3-tert-butyldimethylsilyloxy-2-cyclobutylpropanal. This gave the 4-tert-butyldimethylsilyloxymethyl-4-cyclobutyl-5-isopropenyloxazolidinone with the 5-isopropenyl and 4-tert-butyldimethylsilyloxymethyl groups cis-disposed about the five-membered ring by chelation controlled addition and in situ cyclisation. This reaction was useful for a range of organometallic reagents. The hydroboration–oxidation of (4SR,5RS)-3-benzyl-4-(tert-butyldimethylsilyloxymethyl)-4-cyclobutyl-5-(1-methoxyprop-2-en-2-yl)-1,3-Oxazolidin-2-One gave (4SR,5RS)-3-benzyl-4-(tert-butyldimethylsilyloxymethyl)-4-cyclobutyl-5-[(SR)-1-hydroxy-3-methoxyprop-2-yl]-1,3-Oxazolidin-2-One stereoselectively. 4,7-Diaza-9-oxabicyclo[4.3.0]nonan-8-ones with substituents at C2 that could facilitate C2 deprotonation were unstable with respect to oxazolidinone ring-opening and this restricted both the synthetic approach and choice of 2-heteroaryl substituent. The bicyclic system with a 2-furyl substituent at C2 was therefore identified as an important target. The addition of 1-lithio-1-(2-furyl)ethene to 2-benzyloxycarbonylamino-3-tert-butyldimethylsilyloxy-2-cyclobutylpropanal gave (4SR,5RS)-4-tert-butyldimethylsilyloxymethyl-4-cyclobutyl-5-[1-(2-furyl)ethenyl]-1,3-oxazolidinone after chelation controlled addition and in situ cyclisation. Following oxazolidinone N-benzylation, hydroboration at 35 °C, since hydroboration at 0 °C was unexpectedly selective for the undesired isomer, followed by oxidation gave a mixture of side-chain epimeric alcohols that were separated after SEM-protection and selective desilylation. Conversion of the neopentylic alcohols into the corresponding primary amines by reductive amination, was followed by N-nosylation, removal of the SEM-groups and cyclisation using a Mitsunobu reaction. Denosylation then gave the 2-furyloxazolidinonyl-fused piperidines, the (1RS,2SR,6SR)-epimer showing an allosteric agonistic effect on M1 receptors. Further studies resulted in the synthesis of other 2-substituted 4,7-diaza-9-oxabicyclo[4.3.0]nonan-8-ones and an analogous tetrahydropyran.
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A stereoselective synthesis of a 3,4,5-substituted piperidine of interest as a selective muscarinic (M1) receptor agonist
Synlett, 2015Co-Authors: Kenneth J. Broadley, Maxime G. P. Buffat, Robin H. Davies, Eric J. ThomasAbstract:Syntheses of (1RS,2SR,6SR)-2-alkoxymethyl-, 2-hetaryl-, and 2-(hetarylmethyl)-7-arylmethyl-4,7-diaza-9-oxabicyclo[4.3.0]nonan-8-ones, of interest as potential muscarinic M1 receptor agonists, are described. A key step in the synthesis of (1RS,2SR,6SR)-7-benzyl-6-cyclobutyl-2-methoxymethyl-4,7-diaza-9-oxabicyclo[4.3.0]nonan-8-one, was the addition of isopropenylmagnesium bromide to 2-benzyloxycarbonylamino-3-tert-butyldimethylsilyloxy-2-cyclobutylpropanal. This gave the 4-tert-butyldimethylsilyloxymethyl-4-cyclobutyl-5-isopropenyloxazolidinone with the 5-isopropenyl and 4-tert-butyldimethylsilyloxymethyl groups cis-disposed about the five-membered ring by chelation controlled addition and in situ cyclisation. This reaction was useful for a range of organometallic reagents. The hydroboration–oxidation of (4SR,5RS)-3-benzyl-4-(tert-butyldimethylsilyloxymethyl)-4-cyclobutyl-5-(1-methoxyprop-2-en-2-yl)-1,3-Oxazolidin-2-One gave (4SR,5RS)-3-benzyl-4-(tert-butyldimethylsilyloxymethyl)-4-cyclobutyl-5-[(SR)-1-hydroxy-3-methoxyprop-2-yl]-1,3-Oxazolidin-2-One stereoselectively. 4,7-Diaza-9-oxabicyclo[4.3.0]nonan-8-ones with substituents at C2 that could facilitate C2 deprotonation were unstable with respect to oxazolidinone ring-opening and this restricted both the synthetic approach and choice of 2-heteroaryl substituent. The bicyclic system with a 2-furyl substituent at C2 was therefore identified as an important target. The addition of 1-lithio-1-(2-furyl)ethene to 2-benzyloxycarbonylamino-3-tert-butyldimethylsilyloxy-2-cyclobutylpropanal gave (4SR,5RS)-4-tert-butyldimethylsilyloxymethyl-4-cyclobutyl-5-[1-(2-furyl)ethenyl]-1,3-oxazolidinone after chelation controlled addition and in situ cyclisation. Following oxazolidinone N-benzylation, hydroboration at 35 °C, since hydroboration at 0 °C was unexpectedly selective for the undesired isomer, followed by oxidation gave a mixture of side-chain epimeric alcohols that were separated after SEM-protection and selective desilylation. Conversion of the neopentylic alcohols into the corresponding primary amines by reductive amination, was followed by N-nosylation, removal of the SEM-groups and cyclisation using a Mitsunobu reaction. Denosylation then gave the 2-furyloxazolidinonyl-fused piperidines, the (1RS,2SR,6SR)-epimer showing an allosteric agonistic effect on M1 receptors. Further studies resulted in the synthesis of other 2-substituted 4,7-diaza-9-oxabicyclo[4.3.0]nonan-8-ones and an analogous tetrahydropyran
Bruno Botta - One of the best experts on this subject based on the ideXlab platform.
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Oxazolidin-2-Ones: Antibacterial activity and chemistry
Antimicrobials, 2013Co-Authors: Giovanni Zappia, Cinzia Ingallina, Francesca Ghirga, Bruno BottaAbstract:Since the introduction in the pharmaceutical market of linezolid, an Oxazolidin-2-One based new class of antibacterial agents with a unique mechanism of action, this cyclic carbamate bought a wider popularity and interest for the scientific community. In fact the 1,3-Oxazolidin-2-One nucleus is a popular heterocycle framework in synthetic organic chemistry for its use as chiral auxiliary in stereoselective transformations. This chapter describes the antibacterial activity of linezolid and the status of the activities of other Oxazolidin-2-Ones based antibacterial agents under active clinical investigation. Linezolid and other Oxazolidin-2-One antibacterial agents are currently prepared by chemical synthesis via diverse synthetic routes that have been extensively studied in academic and industrial labs. Biological active Oxazolidin-2-One derivatives are quite rare among natural products.
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Oxazolidin-2-One Ring, a Popular Framework in Synthetic Organic Chemistry Part 2 [1]. Applications and Modifications
Current Organic Synthesis, 2007Co-Authors: Giovanni Zappia, Eszter Gács-baitz, G. Delle Monache, Domenico Misiti, Laura Nevola, G. Cancelliere, Bruno BottaAbstract:The present review is mainly focused upon the use of C-substituted Oxazolidin-2-Ones as chiral auxiliaries in the stereocontrolled C-C and C-X (X = hetero atom) bond formation. The recent progress in the stereoselective alkylation, cycloaddition and aldol reaction, as well as in the 1,4-coniugate addition, in [2+2]-photocycloaddition, in Lewis acid promoted free-radical copolymerization reactions are discussed. Emerging new applications of the Oxazolidin-2-One nucleus, such as building blocks in the design and preparation of foldamers or as organocatalyst in enantioselective epoxidation reactions, will be also discussed. © 2007 Bentham Science Publishers Ltd
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Oxazolidin-2-One Ring, a Popular Framework in Synthetic Organic Chemistry: Part 1. The Construction of the Oxazolidin-2-One Ring
Current Organic Synthesis, 2007Co-Authors: Giovanni Zappia, Eszter Gács-baitz, G. Delle Monache, Domenico Misiti, Laura Nevola, Bruno BottaAbstract:The 1,3-Oxazolidin-2-One nucleus is a popular heterocycle framework in synthetic organic chemistry, as well as in medicinal chemistry. This paper deals with the huge number of synthetic approaches addressed to the construction of this five-member ring, with a particular care for the mechanistic and stereochemical outcome. The 2-oxo-1,3-oxazolidine ring is a cyclic carbamate skeleton quite rare in natural product chemistry but very popular in the Synthetic Organic Chemistry since the Evans' report (1) in 1981 on the use of enantiomerically pure 4- substituted Oxazolidin-2-Ones as chiral auxiliaries in asymmetric synthesis. Oxazolidinones have also a large application as protective groups for the 1,2-aminoalcohol system. Finally, the introduction in the pharmaceutical market of Linezolid (2), an Oxazolidin-2-One-based antibacterial drug, attracted the interest of the scientists and resulted in the production of several publications.
Marina Galdino Da Rocha Pitta - One of the best experts on this subject based on the ideXlab platform.
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Synthesis and in vitro anticancer activity of new 2-thioxo-oxazolidin-4-one derivatives
Pharmacological Reports, 2017Co-Authors: Júlia Furtado Campos, Michelly Cristiny Pereira, Wanessa Layssa Batista De Sena, Caio Gomes De Barros Martins, Jamerson Ferreira De Oliveira, Cezar Augusto Da Cruz Amorim, Moacyr Jesus Barreto De Melo Rêgo, Marina Galdino Da Rocha Pitta, Maria Do Carmo Alves De LimaAbstract:Background Oxazolidinones derivatives exhibit different biological properties, including anticancer activity. This work aimed to investigate the anticancer potential of five novel 2-Thioxo-oxazolidin-4-one derivatives. Methods Cytotoxicity assays were performed in human peripheral blood mononuclear cells (PBMCs) from healthy individuals and seven tumor cell lines. Apoptosis detection and cell cycle were evaluated by flow cytometry and the expression of genes involved in cell death processes by Real-Time PCR. Results All oxazolinedione derivatives were not cytotoxic in PBMCs. NB-5 showed the best results in cancer cells, inhibiting the growth of all tumor cell lines tested. NB-4 exhibited the highest cytotoxicity in Jurkat cells (IC_50 = 15.19 μM) and NB-3 showed better anticancer effects in HL-60 (17.84 μM). Only NB-4 significantly induced apoptosis in acute leukemia cells ( p = 0.001). All compounds caused a significant increase in expression of pro-apoptotic gene BID ( p
