Academic literature on the topic 'Morpholino Chemistry'
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Journal articles on the topic "Morpholino Chemistry"
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Huber, Gerald, Annette Schier, and Hubert Schmidbaur. "The Stereochemistry of Chloro-bis(N-morpholino)phenylsilane." Zeitschrift für Naturforschung B 54, no. 1 (January 1, 1999): 18–20. http://dx.doi.org/10.1515/znb-1999-0106.
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Treatment of phenyltrichlorosilane with an excess of morpholine and N-lithium-morpholide in pentane/toluene affords only the disubstitution product Cl(Ph)Si(Mor)2 with Mor = O(CH2CH2)2N-. The third halogen atom is not replaced owing to sterical hindrance. The title compound crystallizes with two independent molecules in the unit cell. These two molecules can be classified as enantiomers, because a disrotatory twist of the two morpholino ligands away from the potential mirror plane induces a chiral conformation. In benzene solution there is racemization owing to completely free rotation, chair/boat interconversion, and nitrogen inversion of the morpholino groups on the NMR time scale, but all CH2 protons remain anisochronous (diastereotopic).
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Paul, Sibasish, and Marvin H. Caruthers. "Synthesis of Backbone-Modified Morpholino Oligonucleotides Using Phosphoramidite Chemistry." Molecules 28, no. 14 (July 13, 2023): 5380. http://dx.doi.org/10.3390/molecules28145380.
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Phosphorodiamidate morpholinos (PMOs) are known as premier gene knockdown tools in developmental biology. PMOs are usually 25 nucleo-base-long morpholino subunits with a neutral phosphorodiamidate linkage. PMOs work via a steric blocking mechanism and are stable towards nucleases’ inside cells. PMOs are usually synthesized using phosphoramidate P(V) chemistry. In this review, we will discuss the synthesis of PMOs, phosphoroamidate morpholinos (MO), and thiophosphoramidate morpholinos (TMO).
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Hao, Xue-chen, Jiu-fu Lu, Ye Chen, Yang Wang, Shi Ding, and Ju Liu. "Synthesis, Crystal Structure and Antitumour Activity of 3-Amino-N-(5-Fluoro-2-Methylphenyl)-4-Morpholino-1H-Indazole-1-Carboxamide." Journal of Chemical Research 41, no. 11 (November 2017): 624–26. http://dx.doi.org/10.3184/174751917x15065183733178.
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Compound 3-amino- N-(5-fluoro-2-methylphenyl)-4-morpholino-1 H-indazole-1-carboxamide has been synthesised by condensation of 4-fluoro-2-isocyanato-1-methylbenzene with 4-morpholino-1 H-indazol-3-amine, which was prepared from 2,6-difluorobenzonitrile by amination with morpholine and then cyclisation with hydrazine hydrate. The crystal structure of the title compound was determined. In addition, the compound inhibits proliferation of some cancer cell lines.
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Tang, Zhi-hua, and Wei-Jun Fu. "Synthesis, Crystal Structure and Antitumour Activity of 3-Amino-4-Morpholino-1H-Indazol-1-yl(3-Fluorophenyl)Methanone." Journal of Chemical Research 42, no. 11 (November 2018): 552–55. http://dx.doi.org/10.3184/174751918x15402939385990.
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3-Amino-4-morpholino-1H-indazol-1-yl(3-fluorophenyl)methanone was synthesised by condensation of 3-fluorobenzoic acid with 4-morpholino-1H-indazol-3-amine, which was prepared from 2,6-difluorobenzonitrile by amination with morpholine and then cyclisation with hydrazine hydrate. The molecular structure was tested by single crystal X-ray diffraction. Preliminary biological tests showed that the compound possesses distinct inhibition on the proliferation of A549, BGC-823 and HepG-2 cancer cell lines.
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Lu, Jiu-fu, Ling-xia Jin, Hong-guang Ge, Juan Song, Cai-bin Zhao, Xiao-hua Guo, Si-yu Yue, and Li Li. "Synthesis, Crystal Structure and Antitumour Activity of 4-(3-Amino-4-Morpholino-1H-Indazole-1-Carbonyl)Benzonitrile." Journal of Chemical Research 42, no. 6 (June 2018): 309–12. http://dx.doi.org/10.3184/174751918x15287920661730.
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The title compound, 4-(3-amino-4-morpholino-1 H-indazole-1-carbonyl)benzonitrile was synthesised by condensation of 4-cyanobenzoic acid with 4-morpholino-1 H-indazol-3-amine, which was prepared from 2,6-difluorobenzonitrile by amination with morpholine and then cyclisation with hydrazine hydrate. The crystal structure of the title compound was determined and the crystals belong to the monoclinic system, space group P21/ c. In addition, the compound showed some inhibition of the proliferation of some cancer cell lines.
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Ji, Xiao-hui, Ling-xia Jin, Cai-bin Zhao, Nan Zheng, Juan Song, Hong-guang Ge, Quan Liu, and Jiu-fu Lu. "Synthesis, Crystal Structure and Antitumour Activity of 3-Amino-N-[4-chloro-3-(Trifluoromethyl)Phenyl]-4-Morpholino-1H-Indazole-1-Carboxamide." Journal of Chemical Research 42, no. 10 (October 2018): 504–7. http://dx.doi.org/10.3184/174751918x15380423621264.
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Compound 3-amino-N-[4-chloro-3-(trifluoromethyl)phenyl]-4-morpholino-1H-indazole-1-carboxamide has been synthesised by condensation of 1-chloro-4-isocyanato-2-(trifluoromethyl)benzene with 4-morpholino-1H-indazol-3-amine, which was prepared from 2,6-difluorobenzonitrile by amination with morpholine and then cyclisation with hydrazine hydrate. The crystal structure of the title compound was determined. In addition, the compound possesses a distinct inhibitory capacity against proliferation of the A549 and BGC-823 cancer cell lines.
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Lu, Jiu-fu, Xing-long Zhou, Yu-hang Xu, Si-yu Yue, Xiao-hui Ji, Nan Zheng, and Ling-xia Jin. "Synthesis, Crystal Structure, and Biological Activity of 3-Amino-4-Morpholino-N-[2-(Trifluoromethoxy)Phenyl]-1H-Indazole-1-Carboxamide." Journal of Chemical Research 41, no. 9 (September 2017): 526–28. http://dx.doi.org/10.3184/174751917x15033157981988.
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The title compound, 3-amino-4-morpholino- N-[2-(trifuoromethoxy)phenyl]-1 H-indazole-1-carboxamide has been synthesised by condensation of 1-isocyanato-2-(trifluoromethoxy)benzene with 4-morpholino-1 H-indazol-3-amine, which was prepared from 2,6-difluorobenzonitrile by amination with morpholine and then cyclisation with hydrazine hydrate. The crystal of the title compound belongs to the monoclinic system, space group P21/n with a = 11.0292(7) Å, b = 11.4332(8) Å, c = 15.6690(8) Å, α = 90°, β = 102.481(6)°, γ = 90°. In addition, the compound possesses distinct effective inhibition on the proliferation of cancer cell lines.
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Rádl, Stanislav, and Pavel Hradil. "Synthesis of some 1-alkyl-1,4-dihydro-4-oxo-1,7-naphthyridine-3-carboxylic acids." Collection of Czechoslovak Chemical Communications 56, no. 11 (1991): 2420–29. http://dx.doi.org/10.1135/cccc19912420.
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Reaction of substituted 2-aminopyridines IIIa, IIIb, IIIe, and IIIf with ethyl ethoxymethylene malonate provided corresponding pyridylaminomethylenemalonates Va-Vd, respectively. Thermal cyclization of Va, Vc, and Vd yielded substituted ethyl 4-hydroxy-1,7-naphthyridine-3-carboxylates VIa, VIc, and VId. Compounds VIc and VId treated with morpholine gave 8-morpholino derivatives VIe and VIf. These compounds were ethylated to mixtures of N-ethylated (VIIa, VIIb) and O-ethylated products (VIIIa, VIIIb). Compound VIIIb was also prepared from ethyl 4-chloro-6-fluoro-8-morpholino-1,7-naphthyridine-3-carboxylate VIIIc and sodium ethanolate. Esters VIIa and VIIb were hydrolyzed under acidic conditions to the respective acids VIIc and VIId.
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Tiravia, Martina, Federica Sabuzi, Francesca Valentini, Valeria Conte, and Pierluca Galloni. "3-Morpholino-7-[N-methyl-N-(4′-carboxyphenyl)amino]phenothiazinium Chloride." Molbank 2022, no. 4 (November 14, 2022): M1493. http://dx.doi.org/10.3390/m1493.
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The synthesis of 3-morpholino-7-[N-methyl-N-(4′-carboxyphenyl)amino]phenothiazinium chloride is reported here. Interestingly, non-symmetric phenothiazinium salt is functionalized with a carboxylic acid group that allows the easy and stable anchoring on metal oxides. In addition, the morpholine unit reduces the dye aggregation tendency; thus, improving its potential applications in the biomedical and photo-electrocatalytic field.
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Basha, S. Farook, and M. Syed Ali Padusha. "Ultrasonic Studies on the Nature of Molecular Interaction of Synthesized Mannich Bases in DMSO at Different Temperatures." Asian Journal of Chemistry 31, no. 4 (February 27, 2019): 960–64. http://dx.doi.org/10.14233/ajchem.2019.21893.
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This work deals with the ultrasonic studies of the Mannich bases (morpholin-4-yl)(pyridin-3- yl)methyl]hydrazine carboxamide (MPH) and (morpholino)(thiophen-2-yl)methyl)nicotine hydrazide (MTN) by the measurements of parameters such as ultrasonic velocity (U), density (ρ), viscosity (η), adiabatic compressibility (κ), intermolecular free length (Lf), molar volume (Vm), relaxation time (τ), specific acoustic impedance (Z), lenard jones potential (LJP), internal pressure (πi), free volume (Vf) and molecular cohesive energy (MCE), available volume (Va), Gibbs free energy (ΔG) and absorption coefficient (α/f2). These results are inferred that the strong interaction exists between the solvent (DMSO) and solute (MPH and MTN).
Dissertations / Theses on the topic "Morpholino Chemistry"
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Sukackienė, Zita. "Investigation of peculiarities of cobalt and its alloys electroless deposition." Doctoral thesis, Lithuanian Academic Libraries Network (LABT), 2014. http://vddb.library.lt/obj/LT-eLABa-0001:E.02~2014~D_20140701_110312-91991.
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As new technological tasks arise, electroless coatings on the basis of cobalt have come into use in microelectronics and micromechanics in order to form a protective layer against copper migration in integral schemes. Copper possesses a low specific resistance, however it also has some disadvantages, such as a low corrosion resistance and a high diffusion coefficient into So and SiO2 as well as into other substances. These problems can be diminished by using a thin barrier layer protecting from copper diffusion. The barrier properties of CoP and CoB layers which can be further improved by addition of tungsten would be suited for this purpose. At present, investigations of this kind are being carried out in many countries.
Recently much attention is given to the search of new substances, which could be used in direct borohydride fuel cells as catalysts for the borohydride oxidation reaction.
The aim of our work was to investigate the peculiarities of electroless cobalt coatings deposition in glycine solutions using sodium hypophosphite and morpholine borane as reducing agents, as well as to determine the composition of the coatings obtained and the possibilities of their employment for the formation of barrier layers on copper and application for fuel cells production.
It has been determined that using hypophosphite as a reducing agent the rate of CoP and CoWP coatings deposition and the quantity of P in them increases with increase in solution pH. After appropriate... [to full text]Iškilus naujiems technologiniams uždaviniams, chemines dangas kobalto pagrindu, pradėta naudoti mikroelektronikoje ir mikromechanikoje siekiant sudaryti apsauginį sluoksnį vario migracijai integralinėse schemose. Varis turi mažą specifinę varžą, tačiau turi ir keletą trūkumų, tokių kaip blogas korozinis atsparumas ir aukštas difuzijos koeficientas į Si ir SiO2, bei kitas medžiagas. Šios problemos gali būti sumažintos naudojant ploną barjerinį sluoksnį, apsaugantį nuo vario difuzijos. Tam tiktų CoP bei CoB sluoksnių barjerinės savybės, kurias galima pagerinti įvedant volframą. Šiuo metu tokie tyrimai vyksta daugelyje šalių. Taip pat pastaruoju metu skiriamas didelis dėmesys naujų medžiagų paieškai, kurios būtų taikomos tiesioginiuose borohidrido kuro elementuose katalizatoriais borhidrido oksidacijos reakcijai. Mūsų darbo tikslas ištirti kobalto dangų cheminio nusodinimo glicininiuose tirpaluose ypatumus, reduktoriais naudojant natrio hipofosfitą ir morfolino boraną, bei nustatyti gaunamų dangų sudėtį ir jų panaudojimo galimybes barjerinių sluoksnių formavimui ant vario bei taikymui kuro elementų gamybai. Nustatyta, kad naudojant reduktoriumi hipofosfitą didinant tirpalų pH, CoP ir CoWP dangų nusėdimo greitis ir P kiekis jose didėja. Parinkus tinkamas sąlygas buvo gautos kokybiškos kobalto dangos, į kurias patenka nuo 2,9 iki 6,3 at.% P ir nuo 3 iki 5 at.% W. Nustatyta, kad dikarboninės rūgštys gerina tirpalų buferines savybes, pagreitina kobalto dangų nusėdimą ir didina... [toliau žr. visą tekstą]
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Sukackienė, Zita. "Kobalto ir jo lydinių cheminio nusodinimo ypatumų tyrimas." Doctoral thesis, Lithuanian Academic Libraries Network (LABT), 2014. http://vddb.library.lt/obj/LT-eLABa-0001:E.02~2014~D_20140701_110300-61887.
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Iškilus naujiems technologiniams uždaviniams, chemines dangas kobalto pagrindu, pradėta naudoti mikroelektronikoje ir mikromechanikoje siekiant sudaryti apsauginį sluoksnį vario migracijai integralinėse schemose. Varis turi mažą specifinę varžą, tačiau turi ir keletą trūkumų, tokių kaip blogas korozinis atsparumas ir aukštas difuzijos koeficientas į Si ir SiO2, bei kitas medžiagas. Šios problemos gali būti sumažintos naudojant ploną barjerinį sluoksnį, apsaugantį nuo vario difuzijos. Tam tiktų CoP bei CoB sluoksnių barjerinės savybės, kurias galima pagerinti įvedant volframą. Šiuo metu tokie tyrimai vyksta daugelyje šalių.
Taip pat pastaruoju metu skiriamas didelis dėmesys naujų medžiagų paieškai, kurios būtų taikomos tiesioginiuose borohidrido kuro elementuose katalizatoriais borohidrido oksidacijos reakcijai.
Mūsų darbo tikslas ištirti kobalto dangų cheminio nusodinimo glicininiuose tirpaluose ypatumus, reduktoriais naudojant natrio hipofosfitą ir morfolino boraną, bei nustatyti gaunamų dangų sudėtį ir jų panaudojimo galimybes barjerinių sluoksnių formavimui ant vario bei taikymui kuro elementų gamybai.
Nustatyta, kad naudojant reduktoriumi hipofosfitą didinant tirpalų pH, CoP ir CoWP dangų nusėdimo greitis ir P kiekis jose didėja. Parinkus tinkamas sąlygas buvo gautos kokybiškos kobalto dangos, į kurias patenka nuo 2,9 iki 6,3 at.% P ir nuo 3 iki 5 at.% W. Nustatyta, kad dikarboninės rūgštys gerina tirpalų buferines savybes, pagreitina kobalto dangų nusėdimą ir didina... [toliau žr. visą tekstą]As new technological tasks arise, electroless coatings on the basis of cobalt have come into use in microelectronics and micromechanics in order to form a protective layer against copper migration in integral schemes. Copper possesses a low specific resistance, however it also has some disadvantages, such as a low corrosion resistance and a high diffusion coefficient into So and SiO2 as well as into other substances. These problems can be diminished by using a thin barrier layer protecting from copper diffusion. The barrier properties of CoP and CoB layers which can be further improved by addition of tungsten would be suited for this purpose. At present, investigations of this kind are being carried out in many countries. Recently much attention is given to the search of new substances, which could be used in direct borohydride fuel cells as catalysts for the borohydride oxidation reaction. The aim of our work was to investigate the peculiarities of electroless cobalt coatings deposition in glycine solutions using sodium hypophosphite and morpholine borane as reducing agents, as well as to determine the composition of the coatings obtained and the possibilities of their employment for the formation of barrier layers on copper and application for fuel cells production. It has been determined that using hypophosphite as a reducing agent the rate of CoP and CoWP coatings deposition and the quantity of P in them increases with increase in solution pH. After appropriate... [to full text]
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Guardado, Puentes Julian. "Trans diequatorially fused 3',3'-Diphenyl-2'-morpholinone derivatives of 2-Amino-2-deoxy-D-glucose." Scholarly Commons, 1985. https://scholarlycommons.pacific.edu/uop_etds/2113.
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The chemistry of amino sugar compounds has been studied in the last years in connection with the study of natural products, and many of them have been isolated. 57,17,18 Amino sugars play an important role in biochemistry, forming blocks of homo- and heteropolymers and complex molecules such as microbial polysaccharides, enzymes, gangliosides, glycoproteins, and antibiotics.
This research project had the purpose of preparing a derivative of 2-amino-2-deoxy-D-glucose, with a free hydroxyl group at the anomeric carbon, with the 4,6-positions blocked with the benzylidene cyclic acetal, and the 2,3-positions being blocked by a 3,3-diphenyl-2-morpholinone ring trans diequatorially fused to the amino sugar ring. The C-1 position was initially protected with a β-benzyl aglycon, which was expected to be removable selectively by catalytic hydrogenation. It was also hoped that we could optimize conditions for the synthesis of the morpholinone derivative. Selective cleavages of the blocking groups were to be investigated.
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Duchamp, Edouard. "Nouvelles exploitations des tétrazoles comme précurseurs en synthèse organique: accès aux morpholines, cyanamides et produits naturels." Thesis, 2021. http://hdl.handle.net/1866/25560.
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Les cycles azotés font partie intégrante de la vie sur Terre. Cette thématique est transcrite dans les travaux de cette thèse à travers les tétrazoles et les morpholines.
Les morpholines sont des azacycles saturés possédant de nombreuses propriétés physico-chimiques et structurales intéressantes, ce qui en fait un motif de choix en chimie médicinale. L'essor des morpholines est d'autant plus important que les industries pharmaceutiques tendent à limiter l'utilisation de cycles insaturés au profit de motifs permettant des structures plus complexes et occupant les trois dimensions de l'espace. Ainsi, le développement de nouvelles voies d'accès aux morpholines est contemporain. La contribution présentée dans ce manuscrit s'appuie sur la réduction de tétrazoles oxabicycliques par des hydrures. Le mécanisme du clivage réductif du tétrazole en amine a par ailleurs été étudié et élucidé.
Les cyanamides forment un groupement fonctionnel intéressant grâce à leur nature électronique ambivalente. Elles sont de plus en plus utilisées en chimie médicinale en tant qu'inhibiteurs covalents. Alors que les cyanamides ont été découvertes à l'aube de la chimie organique, leurs synthèses ont traditionnellement eu recours à des sources de cyanure, composé extrêmement toxique. La métallation en position 5 des tétrazoles 1-substitués permet d'induire la rétrocyclisation spontanée conduisant à l'expulsion d'une molécule de diazote et d'un sel de cyanamidure. Ce sel a pu être isolé ou alkylé in situ, offrant une nouvelle voie d'accès aux cyanamides sans source de cyanure. Les cyanamides ainsi obtenues ont pu être diversifiées en amidines par addition d'organolithiens.
La Polygonapholine est un alcaloïde contenant une morpholine 2,6-disubstituée isolé en 1997. La structure rapportée est probablement erronée et seule une synthèse en laboratoire peut confirmer son exactitude. Ainsi, la première synthèse totale de ce produit naturel a été débutée et est présentée dans le dernier chapitre de ce manuscrit.Nitrogen-containing rings are core entities in the living world. This theme is conveyed in the manuscript through tetrazoles and morpholines. Morpholines are saturated azacycles possessing numerous physico-chemical and structural properties, which makes them a motif of interest in medicinal chemistry. The impact of morpholines is even more important as pharmaceutical industries try to avoid overuse of unsaturated rings in favor of saturated motifs that allow for more complex structures in the three dimensions. Therefore, development of new methods to access morpholines is an ongoing activity in many laboratories. The approach presented herein relies on the hydride reduction of oxabicyclic tetrazoles to morpholines. A detailed mechanism of the reductive cleavage of the tetrazole unit is presented. Cyanamides are endowed with an ambident electronic character that adds value to this functional group. They are widely used in drug design as covalent inhibitors. Even though cyanamides were discovered in late 19th century, their synthesis has traditionally relied on the cyanation of amines using toxic cyanide reagents. 1-Substituted 5-metalotetrazoles undergo rapid cycloreversion releasing dinitrogen and forming N-metalated cyanamide salts. The salts can be isolated or alkylated in situ, providing a new method for accessing cyanamides without the use of cyanide reagents. The obtained cyanamides could be subjected to an addition reaction with organolithium reagents, thereby yielding novel amidines. The alkaloid Polygonapholine is a 2,6-disubstituted morpholine isolated in 1997. The reported structure has never been confirmed, nor has the natural product been synthesized in the laboratory. Efforts towards its total synthesis and stereochemical confirmation is presented in the last chapter of the thesis.
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Hocine, Sofiane. "Design et synthèse des composés azabicycliques contraints : de la chimie médicinale à la catalyse." Thesis, 2020. http://hdl.handle.net/1866/24767.
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Les azacycles tels que les morpholines ou les pyrrolidines, sont très répandus dans le domaine de l’organocatalyse et de la chimie médicinale. Cette thèse traitera d’analogues contraints de ces azacycles, qui peuvent moduler de par leurs structures, les propriétés de certains médicaments ou la sélectivité de certaines réactions.
Le cas de l’halopéridol, qui est connu pour son activité sur les récepteurs dopaminergiques D2 et D4, est au centre de la première partie de cette thèse, dans laquelle de nouveaux analogues contraints de type 2-oxa-5-azabicyclo[2.2.2]octane ont été développés pour pallier ses problèmes de stabilité métabolique.
Dans une seconde partie, la synthèse de deux nouvelles chimères morpholine-proline pontées est rapportée. Leurs structures rigides et conformationnellement verrouillées permettent aux doublets d’électrons non liants sur les atomes d'azote et d'oxygène d’être respectivement orientés dans des directions « Est-Ouest » et « Nord-Est » spatialement différentes. En combinaison avec la présence d'un acide carboxylique, les propriétés électroniques de ces composés peuvent être utiles dans le contexte de la conception peptidomimétique de composés biologiquement pertinents. Des estimations quantitatives de la basicité des atomes d'azote ont été obtenues en utilisant une analyse DFT conceptuelle.
Dans la troisième partie de cette thèse, la synthèse de nouvelles pyrrolidines oxabicycliques sera développée. Les cyclopentan[c]pyrroles sont très répandus dans la littérature, et connus pour leurs propriétés analgésiques. Des dérivés fonctionnalisés en positions 4 et 5, synthétisés par Servier, ont notamment présenté de bonnes activités en tant que ligands nicotiniques 7, mais aussi des problèmes d’inhibition de hERG. Afin d’obtenir des composés moins lipophiles et donc de pallier les problèmes d’inhibition hERG, de nouveaux analogues oxygénés de type furo[2,3-c]pyrroles ont été développés par différentes voies de synthèse. Ces nouveaux composés pourront notamment être obtenus sous formes énantiomériquement enrichies, grâce à une étape clé de résolution enzymatique.
La proline a été largement utilisée ces dernières années comme organocatalyseur au sein d’importantes transformations asymétriques comme les aldolisations ou les additions de Michael. Cependant, malgré le succès de ce motif, plusieurs de ses dérivés ont été rapportés dans la littérature. C’est notamment le cas des 4,5-méthanoprolines qui furent rapportées pour la première fois par Hanessian en 1997, dont l’efficacité en tant qu’organocatalyseur pour la réaction de Hajos-Parrish ainsi que plusieurs autres types de réaction fut par la suite établie. Les dernières parties de cette thèse viennent compléter ces études. La synthèse de nouvelles 4,5-ethanoprolines a été développée, ainsi que leurs utilisations comme catalyseur lors de réactions de Hajos-Parrish et d’addition catalytique asymétrique de nitroalcanes sur des énones cycliques. Une étude DFT a été effectuée afin d’expliquer l’inversion de sélectivité observée pour ces nouveaux catalyseurs lors des réactions de Hajos-Parrish, le mécanisme de formation des énamines réactives a aussi été investigué.Azacycles such as morpholines and pyrrolidines, are very widespread in chemistry, especially in the fields of organocatalysis and medicinal chemistry. This thesis will deal with constrained analogues of those azacycles, which, depending on their structures, can modulate the properties of certain drugs or the selectivity of certain reactions. The case of haloperidol, which is known for its activity on the dopamine D2 and D4 receptors, is at the center of the first part of this thesis, in which new constrained analogs of the 2-oxa-5-azabicyclo type [2.2.2] octane have been developed to overcome its metabolic stability problems. In a second part, the synthesis of two new bridged morpholine-proline chimeras are reported. Their rigid structures allow the lone pairs on the nitrogen and oxygen atoms to be oriented in spatially different "East-West" and "North-East" directions, respectively. In combination with the presence of a carboxylic acid, the electronic properties of these compounds could be useful in the context of the design of biologically relevant peptidomimetics. Quantitative estimations of the basicity of the nitrogen atoms were obtained using DFT analysis. In the third part of this thesis, the synthesis of new oxabicyclic pyrrolidines is described. Cyclopentan[c]pyrroles are widely encountered and known for their analgesic properties. The Servier laboratories have synthesized derivatives with substituents at positions 4 and 5, exhibiting good activities as 7 nicotinic ligands, but problems of hERG inhibition. In order to obtain less lipophilic compounds and therefore overcome the problems of hERG inhibition, new oxygenated analogs of the furo[2,3-c]pyrrole type have been developed by different synthetic routes. These new compounds were obtained in enantiomerically enriched forms, using enzymatic resolution. Proline has been widely used in recent years as an organocatalyst in asymmetric transformations such as aldolizations or Michael additions The success of this motif, has inspired synthesis of derivatives, such as 4,5-methanoprolines, which were first reported by Hanessian in 1997, and shown to be effective as organocatalysts in the Hajos-Parrish and other reactions. The last parts of this thesis develop further these studies by the synthesis of new 4,5-ethanoprolines which act as a catalysts in the Hajos-Parrish reaction and the asymmetric catalytic addition of nitroalkanes to cyclic enones. A DFT study was carried out to explain the reversal of selectivity observed for the new catalysts in Hajos-Parrish reaction and to investigate formation of a reactive enamine in the mechanism.
Book chapters on the topic "Morpholino Chemistry"
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Palacio-Castañeda, Valentina, Roland Brock, and Wouter P. R. Verdurmen. "Generation of Protein-Phosphorodiamidate Morpholino Oligomer Conjugates for Efficient Cellular Delivery via Anthrax Protective Antigen." In Methods in Molecular Biology, 129–41. New York, NY: Springer US, 2022. http://dx.doi.org/10.1007/978-1-0716-2010-6_8.
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AbstractPhosphorodiamidate morpholino oligomers (PMOs) offer great promise as therapeutic agents for translation blocking or splice modulation due to their high stability and affinity for target sequences. However, in spite of their neutral charge as compared to natural oligonucleotides or phosphorothioate analogs, they still show little permeability for cellular membranes, highlighting the need for effective cytosolic delivery strategies. In addition, the implementation of strategies for efficient cellular targeting is highly desirable to minimize side effects and maximize the drug dose at its site of action. Anthrax toxin is a three-protein toxin of which the pore-forming protein anthrax protective antigen (PA) can be redirected to a receptor of choice and lethal factor (LF), one of the two substrate proteins, can be coupled to various cargoes for efficient cytosolic cargo delivery. In this protocol, we describe the steps to produce the proteins and protein conjugates required for cytosolic delivery of PMOs through the cation-selective pore generated by anthrax protective antigen. The method relies on the introduction of a unique cysteine at the C-terminal end of a truncated LF (aa 1–254), high-yield expression of the (truncated) toxin proteins in E. coli, functionalization of a PMO with a maleimide group and coupling of the maleimide-functionalized PMO to the unique cysteine on LF by maleimide-thiol conjugation chemistry. Through co-administration of PA with LF-PMO conjugates, an efficient cytosolic delivery of PMOs can be obtained.
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Kumari, Archana, and Rajesh K. Singh. "Morpholine: Pharmacophore Modulating Pharmacokinetic Properties of Anticancer Leads." In Key Heterocyclic Cores for Smart Anticancer Drug–Design Part II, 137–73. BENTHAM SCIENCE PUBLISHERS, 2022. http://dx.doi.org/10.2174/9789815040043122020008.
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The morpholine ring is considered the most preferred and versatile heterocylic ring in medicinal chemistry due to its distinctive mechanistic activities that give it various biological activities. The eminence of the morpholine ring to modulate the pharmacokinetic properties of the compound, further makes it a fundamental pharmacophore in developing lead molecules. Multi-drug resistance in cancer leads to discovering selective and potent chemotherapeutic agents. Researchers are designing and synthesizing morpholine derivatives as potential anticancer drugs those act by targeting various signaling pathways driven by various protein kinases in the cell, i.e. Ras-Raf-MEK-ERK (ERK) and PI3K/Akt/mTOR, thereby inhibiting cell proliferation and growth. The potency of natural and synthetic derivatives of morpholine makes it a drug of choice for cancer treatment. Many of the morpholine containing anticancer drugs are under clinical trials. Hence, morpholine ring synthesis also becomes a central target for various scientists using green synthesis by straightforward one-step methods. A substantial literature is available on synthetic techniques of morpholine and substituted morpholine. The present chapter updates diverse new synthetic strategies of the morpholine ring and morpholine derivatives with potent anticancer activity. The chapter will also highlight the clinical data of morpholine derivatives with anticancer activity and mechanism of action. The latest information on novel anticancer morpholine derivatives with structural activity relationship (SAR) is also included. This chapter provides information about the necessary structural modifications required in drugs' chemical structure and contribute to the anticancer drug discovery program.
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DeRosa, Thomas F. "Morpholines." In Advances in Synthetic Organic Chemistry and Methods Reported in US Patents, 399–400. Elsevier, 2006. http://dx.doi.org/10.1016/b978-008044474-1/50054-2.
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Kumbhar, A. G., S. Rangarajan, S. V. Narasimhan, P. K. Mathur, and K. S. Venkateswarlu. "Paper 100. Evaluation of condensate demineralisation using morpholine form of the cation exchanger." In WATER CHEMISTRY OF NUCLEAR REACTOR SYSTEMS 4, 363–67. Thomas Telford Publishing, 1986. http://dx.doi.org/10.1680/wconrs4v1.03705.0074.
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Dauvois, V., I. Lambert, D. Desmoulins, and F. Nordmann. "Paper 101. Laboratory and plant investigations on decomposition products of morpholine in the secondary system of French PWRs." In WATER CHEMISTRY OF NUCLEAR REACTOR SYSTEMS 4, 372–75. Thomas Telford Publishing, 1986. http://dx.doi.org/10.1680/wconrs4v1.03705.0075.
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Lambert, Tristan H. "C–O Ring Formation." In Organic Synthesis. Oxford University Press, 2017. http://dx.doi.org/10.1093/oso/9780190646165.003.0044.
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The enantioselective bromocyclization of dicarbonyl 1 to form dihydrofuran 3 using thiocarbamate catalyst 2 was developed (Angew. Chem. Int. Ed. 2013, 52, 8597) by Ying-Yeung Yeung at the National University of Singapore. Access to dihydrofuran 5 from the cyclic boronic acid 4 and salicylaldehyde via a morpholine-mediated Petasis borono-Mannich reaction was reported (Org. Lett. 2013, 15, 5944) by Xian-Jin Yang at East China University of Science and Technology and Jun Yang at the Shanghai Institute of Organic Chemistry. Chiral phosphoric acid 7 was shown (Angew. Chem. Int. Ed. 2013, 52, 13593) by Jianwei Sun at the Hong Kong University of Science and Technology to catalyze the enantioselective acetalization of diol 6 to form tetrahydrofuran 8 with high stereoselectivity. Jan Deska at the University of Cologne reported (Org. Lett. 2013, 15, 5998) the conversion of glutarate ether 9 to enantiopure tetrahydrofuranone 10 by way of an enzymatic desymmetrization/oxonium ylide rearrangement sequence. Perali Ramu Sridhar at the University of Hyderabad demonstrated (Org. Lett. 2013, 15, 4474) the ring-contraction of spirocyclopropane tetrahydropyran 11 to produce tetrahydrofuran 12. Michael A. Kerr at the University of Western Ontario reported (Org. Lett. 2013, 15, 4838) that cyclopropane hemimalonate 13 underwent conversion to vinylbutanolide 14 in the presence of LiCl and Me₃N•HCl under microwave irradiation. Eric M. Ferreira at Colorado State University developed (J. Am. Chem. Soc. 2013, 135, 17266) the platinum-catalyzed bisheterocyclization of alkyne diol 15 to furnish the bisheterocycle 16. Chiral sulfur ylides such as 17, which can be synthesized easily and cheaply, were shown (J. Am. Chem. Soc. 2013, 135, 11951) by Eoghan M. McGarrigle at the University of Bristol and University College Dublin and Varinder K. Aggarwal at the University of Bristol to stereoselectively epoxidize a variety of aldehydes, as exemplified by 18. The amine 20-catalyzed tandem heteroconjugate addition/Michael reaction of quinol 19 and cinnamaldehyde to produce bicycle 21 with very high ee was reported (Chem. Sci. 2013, 4, 2828) by Jeffrey S. Johnson at the University of North Carolina, Chapel Hill. Quinol ether 22 underwent facile photorearrangement–cycloaddition to 23 under irradiation, as reported (J. Am. Chem. Soc. 2013, 135, 17978) by John A. Porco, Jr. at Boston University and Corey R. J. Stephenson, now at the University of Michigan.
Conference papers on the topic "Morpholino Chemistry"
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Saleh, Amer F., Andrey A. Arzumanov, Haifang Yin, Corinne Betts, Suzan Hammond, Matthew J. A. Wood, and Michael J. Gait. "Enhancement of exon skipping and dystrophin production by 3'-peptide conjugates of morpholino (PMO) oligonucleotides in a mdx mouse model of Duchenne muscular dystrophy." In XVth Symposium on Chemistry of Nucleic Acid Components. Prague: Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, 2011. http://dx.doi.org/10.1135/css201112292.
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Testa, Maria Luisa, Elena Zaballos-Garcia, and Ramón Zaragozá. "Solvent-mediated reactivity of b-aminoalcohols against dialkyloxalate: synthesis of tetrasubstituted oxalamide and/ or morpholin-2,3-dione derivatives." In The 12th International Electronic Conference on Synthetic Organic Chemistry. Basel, Switzerland: MDPI, 2008. http://dx.doi.org/10.3390/ecsoc-12-01198.
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Brychtova, Katerina, Jozef Csollei, Josef Jampilek, Radka Opatrilova, Lukas Placek, Barbora Slaba, and Sylva Dittrichova. "Synthesis of Esters of 6-(2,5-Dioxopyrrolidin-1-yl)-2- (morpholin-4-yl)hexanoic Acid as Potential Transdermal Penetration Enhancers." In The 13th International Electronic Conference on Synthetic Organic Chemistry. Basel, Switzerland: MDPI, 2009. http://dx.doi.org/10.3390/ecsoc-13-00210.
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