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dc.contributor.authorAlmeida, Paulo Afonso de
dc.date.accessioned2023-12-21T18:59:13Z-
dc.date.available2023-12-21T18:59:13Z-
dc.date.issued2004-03-12
dc.identifier.citationAlmeida, Paulo Afonso de. Mesoiônicos da Classe 1,3-Ditiólio-4-Tiolatos: síntese, reações de cicloadição 1,3-Dipolar e estudo do efeito hidrofóbico. 2004. 257 f. Tese (Programa de Pós-Graduação em Química) - Universidade Federal Rural do Rio de Janeiro, Seropédica-RJ.por
dc.identifier.citationAlmeida, Paulo Afonso de. Mesoiônicos da Classe 1,3-Ditiólio-4-Tiolatos: síntese, reações de cicloadição 1,3-Dipolar e estudo do efeito hidrofóbico. 2004. 257 f. Tese (Programa de Pós-Graduação em Química) - Universidade Federal Rural do Rio de Janeiro, Seropédica-RJ.por
dc.identifier.urihttps://rima.ufrrj.br/jspui/handle/20.500.14407/10230-
dc.description.abstractOs compostos mesoiônicos despertam muito a atenção por serem heterocíclicos dipolares de estruturas não convencionais, apresentando uma atividade biológica muito diversificada e, também, por serem intermediários em reações de cicloadição, para a obtenção de novos derivados heterocíclicos. Neste trabalho foram sintetizados 17 novos derivados mesoiônicos, da classe dos 1,3-ditiólio-4-tiolatos, incluindo uma série homóloga de 13 derivados 2-N-morfolino-5- alquil-1,3-ditiólio-4-tiolatos. Os derivados 2-N-morfolino-5-etil-1,3-ditiólio-4-tiolatos e 2-N-morfolino-5- tetradecil-1,3-ditiólio-4-tiolatos foram submetidos a reações de cicloadição 1,3-dipolar frente a dipolarófilos usuais, como DMAD e ácido fenilpropiólico, gerando 8 novos derivados tiofênicos. Todos os novos derivados mesoiônicos e tiofênicos foram devidamente caracterizados por pontos de fusão, técnicas espectroscópicas de IV, RMN de 1H e 13C (incluindo técnicas heteronucleares bidimensionais) e técnica espectrométrica de massas. A espectrofotometria de UV foi utilizada somente para os derivados mesoiônicos da série homóloga. Todos os derivados mesoiônicos foram submetidos a ensaios de toxicidade geral frente a Artemia salina Leach. Foi feito um estudo do efeito hidrofóbico dos derivados mesoiônicos da série homóloga 5-alquil substituídos, correlacionando-se a toxicidez geral frente a Artemia salina versus o número de carbonos da cadeia alquílica e também versus a hidrofobicidade na forma de logPpor
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico - CNPqpor
dc.formatapplication/pdf*
dc.languageporpor
dc.publisherUniversidade Federal Rural do Rio de Janeiropor
dc.rightsAcesso Abertopor
dc.subjectSíntesepor
dc.subjectCompostos Mesoiônicospor
dc.subjectReações de Cicloadição 1,3-Dipolarpor
dc.subjectEfeito Hidrofóbicopor
dc.subjectToxidez geralpor
dc.subjectArtemia salinapor
dc.subjectSinthesiseng
dc.subjectMesoionic compoundseng
dc.subjecthydrophobic effecteng
dc.subjectArtemia salinaeng
dc.subjectheterocyclic derivativeseng
dc.subject1,3-dipolar cycloaddition reactionseng
dc.titleMesoiônicos da Classe 1,3-Ditiólio-4-Tiolatos: síntese, reações de cicloadição 1,3-Dipolar e estudo do efeito hidrofóbicopor
dc.title.alternativeMesoionic Derivatives from the 1,3-Dithiolium- 4- Thiolate Class: Synthesis, 1,3-Dipolar Cycloaddition Reactions and Hydrophobic Effect Studypor
dc.typeTesepor
dc.description.abstractOtherThe mesoionic compounds have been receiving much attention because of their dipolar special structures and wide-ranging biological activities, they have also being utilized as cycloaddition reactions intermediates to afford new heterocyclic derivatives. In this work 17 new mesoionic derivatives were synthesised from the 1,3- dithiolium-4-thiolate class, including a homologous series of 13 2-N-morpholino-5- alkyl-1,3-dithiolium-4-thiolate. The 2-N-morpholino-5-ethyl- and 2-N-morpholino-5-tetradecyl-1,3- dithiolium-5-thiolates were submitted at 1,3-dipolar cycloaddition reactions against DMAD and phenylpropiolic acid as dipolarophiles affording 8 new thiophenic derivatives. The experimental results were in agreement with the theoretical studies employing semi-empirical molecular modelling methods. All heterocyclic derivatives were fully characterised by spectroscopic techniques, IR, 1H and 13C NMR (1D and 2D experiments) and MS. The UV spectroscopy was utilised only for the homologous mesoionic series. The mesoionic derivatives were assayed against Artemia salina Leach in the general toxicity tests. The hydrophobic effect was studied on mesoionic derivatives of the 5-alkyl homologous series, correlating the Artemia salina general toxicity versus lateral chain number carbon atoms, and the logP values. The results indicated a bell-shaped relationship between the number of carbon of side chain in mesoionic derivatives and LD50 in brine shrimp toxicity assays. The experimental results were in agreement with the theoretical studies which were employing semi-empirical molecular modelling methods. All heterocyclic derivatives were fully characterized by spectroscopic techniques, IR, 1H and 13C NMR (1D and 2D experiments), and MS. The UV spectroscopy was utilized only for the homologous mesoionic serieseng
dc.contributor.advisor1Lima, Aurea Echevarria Aznar Neves
dc.contributor.advisor1Latteshttp://lattes.cnpq.br/1879077396134052por
dc.contributor.referee1Lima, Aurea Echevarria Aznar Neves
dc.contributor.referee2Braz Filho, Raimundo
dc.contributor.referee3Boechat, Núbia
dc.contributor.referee4Lima, Marco Edilson Freire de
dc.contributor.referee5Costa, João Batista Neves da
dc.creator.Latteshttp://lattes.cnpq.br/4266221191908452por
dc.publisher.countryBrasilpor
dc.publisher.departmentInstituto de Ciências Exataspor
dc.publisher.initialsUFRRJpor
dc.publisher.programPrograma de Pós-Graduação em Químicapor
dc.relation.referencesARÉVALO, M. J; ÁVALOS, M.; BABIANO, R.; CINTAS, P.; HURSTHOUSE, M. B.; JIMÉNES, J. L.; LIGHT, M.E.; LOPEZ, I. e PALACIOS, J. C. [3+2]- Cycloaddition of 2-Aminothioisomünchnones to Alkynes: Synthetic Scope and Mechanistic Insights. Tetrahedron. v. 56, p.1247-1255. 2000. ARÉVALO, M. J; ÁVALOS, M.; BABIANO, R.; CINTAS, P.; HURSTHOUSE, M. B.; JIMÉNES, J. L.; LIGHT, M .E.; LOPEZ, I. e PALACIOS, J. C., Expeditious Formation of 1,2,4-Triazine Derivatives via a Thioisomünchnone Cycloaddition Reactions. Tetrahedron Lett. v. 40, p. 8675-8678. 1999. ÁVALOS, M.; BABIANO, R.; CABANILLAS, A.; CINTAS, P.; HIGES, F. J.; JIMÉNES, J. L. e PALACIOS, J. C. Cycloaddition Chemistry of 1,3- Thiazolium-4-olate Systems. Reaction With Nitroalkenes and Interpretation of Results Using PM3 Calculations. J. Org. Chem. v.61, p.3738-3748. 1996. ÁVALOS, M.; BABIANO, R.; CINTAS, P.; CLEMENTE, F. R.; GORDILHO, R.; JIMÉNES, J. L.; PALACIOS, J. C e RAITHBY, P. R. Diastereoselective Cycloadditions of 1,3-Thiazolium-4-olates With Chiral 1,2-Diaza-1,3- butadienes. J. Org. Chem. v.65, p.5089-5097. 2000. ÁVALOS, M.; BABIANO, R.; CINTAS, P.; HURSTHOUSE, M. B.; JIMÉNES, J. L.; LIGHT, M. E.; LOPEZ, I. e PALACIOS, J. C., Chem. commun. p.1589- 1590. 1999. BARREIRO, E. J. & C. FRAGA, A. M. Química Medicinal: As Bases Moleculares da Ação dos Fármacos. Porto Alegre: Artmed : 2001. BAKER, W., OLLIS, W. D. & POOLE, V. D., J. Chem. Soc. 1542. 1950. BERGERS, W. W.; VAN DER STAP, J. G. M. M. e KIENTZ, C. E. Appl. Environ. Microbiol. v. 50, no. 3, p. 656-662. 1985. BESTHORN, E. & IBELE, J., Ber. v.37, p. 1236 .1904. BIER, O. Bacteriologia e Imunologia. 12 ed. São Paulo: Edições Melhoramentos. p. 950-953. 1965. BREITMAIER, E. & W. VOELTER. Carbon-13 NMR Spectroscopy: Hight-Resolution Methods and Applications in Organic Chemistry and Biochemistry. 3rd edition. Weinheim: VCH, 1987. CAREY, F. A. & SUNDBERG, R. J. Advanced Organic Chemistry, Part A: Structure and Mechanisms. 3rd edition. New York, N.Y.: Plenum Press, p. 625-640. 1993. COLGATE, S. M. & MOLYNEUX, R. J. Bioative Natural Products: Detection, Isolation and Structural Determination. COLEGATE, S. M. (ed). London: CRC Press. p. 441. 1993. DELLA CROCE, P. & LA ROSA, R. Stereoselective Synthesis of N-phenylsufonyl Substituted Spiro-b-lactamas. Tetrahedron Asym. v. 10, p.1193-1199 1999. DELLA CROCE, P.; FERRACIOLE, R. e LA ROSA, R. Reactions of Mesoionic Compounds Derivatives from Cyclic N-Acyl-a-Aminoacids With N- (Phenylmethylene)benzenesulfonamide. Tetrahedron, v. 55, p. 201-210. 1999. DEWICK, P. M., Medicinal Natural Products: A Biosynthetic Approach. London: Wiley & Sons Ltd. p. 342-350. 1998. 86 ENGISH JR., J. & CASSIDY, H. G. Principles of Organic Chemistry: Un introductory Text in Organic Chemistry. 2nd Edition. New York: Mcgraw-Hill Book Company, Inc. p. 228. 1956. EARL, J. C. & MACKNEY, A W., J. Chem. Soc. 899. 1935. FERREIRA, C. M.; OLIVEIRA, M. C. C.; VELANDIA, J. R. e ECHEVARIA, A. Química Nova. v. 23, p. 20. 2000. FISCHER, E. & BESTHORN, E., Ann., v. 212, p. 316. 1882. GODFROID, JEAN-JACQUES; BROQUET, C.; JOUQUET, S.; LEBBAR, M.; HEYMANNS, F.; REDEUILH, C.; STEINER, E.; MICHEL, E.; COEFFIER,E.; FICHELLE, J. e WORCEL, M. J. Med. Chem. v. 30, p. 792-797. 1987. GRYNBERG, N.; SANTOS, A. C. e ECHEVARRIA, A. Synthesis and in vivo Antitumor Activity of New Heterocyclic Derivatives of the 1,3,4- Thiadiazolium-2-aminide Class. Anti-cancer Drugs. v. 8, p. 88-91. 1997. GRYNBERG, N.; GOMES, R.; SHINZATO, T.; ECHEVARRIA, A e MILLER, J., Some New Aryl-Sydnones: Effects on Murine Tumours. Anticancer Res. v. 12, p. 1025-1028. 1992. GUYTON, A. C. & HALL, J. E. Guyton & Hall Tratado de Fisiologia Médica. 9 ed. Rio de Janeiro: Guanabara-Koogan, Cap. 2, 1997. HAJID, P.A. ; DEFEYTER, P. J. F.; VAN Der Wall, E. E.; WARDEH, R. e ROOS, J. P. N. Engl. J. Med., v.302, p.1-6. 1995. HANSCH, A. & LEO J. Exploring QSAR: Fundamentals and Applications in Chemistry and Biology. New York: ACS: 1995. HARDMAN, J. G.; LIMBIRD, L. E.; MOLINOFF, P. B e RUDDON, R. W., Goodman & Gilman: As Bases Farmacológicas da Terapêutica, 9 ed.(português). México-DF: Mcgraw-Hill Interamericana Editores S.A, p. 503. 1996. HOLM, P.; KANKAANRANTA, H.; METSÄ-KETELÄ, T. e MOILANEN, E. Radical Releasing Properties of Nitric Oxide Donors GEA 3162, SIN-1 and SNitroso-N-Acetylpenicillamine. Eur. J. Org. Chem. v. 346, p. 97-102. 1998. HWANG, San-Bao. Identification of a Second Putative Receptor of Platelet-Activating Factor from Human Polymorphonuclear Leukocytes. J. Biol. Chem. v. 263, n. 7, p. 3225-3233. 1988. KANKAANRANTA, H.; RYDELL, E.; PETERSSON, A. –S.; HOLM, P.; MOILANEN, E.; CORELL, T.; KARUP, G.; VUORINEN, P.; PEDERSEN, S. B.; WENNMALM, A. e METSÄ-KETELÄ, T. Nitric Oxide-Donating Properties of Mesoionic 3-Aryl Substituted Oxatriazole-5- Imine Derivatives. Br. J. Pharmacol. , v. 117, p. 401-406. 1996. KAPPE, C. O.; PETERS, K. e PETERS, Eva-Maria. Dipolar Cycloaddition Reactions of Dihydropyrimidine-Fuzed Mesoionic Betaines. Na Approach Toward Conformationally Restricted Dihydropyrimidine Derivatives. J. Org. Chem. v. 62, p. 3109-3118. 1997. KIER, L. B. & ROCHE, E. B. J. Pharm. Sci. v.56, p. 149. 1967. LÄHTEENMÄKI, T.; SIEVI, E. E VAPAATALO, H. Inhibitory Effefcts of Mesoionic 3-Aryl Substituted Oxatriazole-5-imine Derivatives on Vascular Smooth Cell Mitogenesis and Proliferation in vivo. Br. J. Pharmacol., v.125, p. 402-408. 1998. 87 LODISH, H.; BALTIMORE,D.; BERK, A.; ZIPURSKY, S.; L.; MATSUDAIRA, P. e DARNELL, J. Molecular Cell Biology. 3rd edition. New york: Scientific American Books, p. 595. 1995. MACKIE, R. K.; SMITH, D. M. E AITKEN, R. A., Guidebook to Organic Synthesis. 2nd edition. London: Longman Group UK. 1990. MARINO JR, J. P.; OSTERHOUT, M. H. e PADWA, A. An Approach to Lysergic Acid Utilizing na Intramolecular Isomünchnone Cycloaddition Pathway. J. Org. Chem. v. 60, p. 2704-2713. 1995. MARTIN, Y. C. Quantitative Drug Design – A Critical Introduction. REKKER, M. (eds). USA: p. 257.1987. MEYER, B. N.; FERRIGNE, N. R.; PUTNAN, J. E.; JACOBSEN, D. E.; MCLAUGHIIN, L. Planta Medica. v. 45, p. 31. 1982. NAKANISHI, K. & SOLOMON, P. H. Infrared Absorption Spectroscopy; 2nd edition. Oakland: Holden-Day, Inc. p. 47. 1977. NEWTON, C. G. & RAMSDEN, C. A. Meso-ionic Heterocycles (1976-1980). Tetrahedron. v. 38, n.20, p. 2965-301. 1982. OLLIS, W. D. & RAMSDEM, C. A., Adv. Hetercycl. Chem. v.19, p.1. 1976. OLLIS, W. D. & RAMSDEN, C. Adv. Heterocycl. Chem., v. 19, p. 3. 1976. OLIVEIRA, M. B. de; MILLER, J.; PERREIRA, A. B.; GALEMBECK, S. E; MOURA, G. L. De e SIMAS, A. M. Mesoionic 2-N-Cycloalkylamino-5- Alkyl-1,3-Dithiolium-4-Thiolates. Phosphorus, Sulfur and Silicon. v.108, p.75-84. 1996. OSTERHOUT, M. H.; NADLER, W. R. e PADWA, A. Recent Advances in the Cycloaddition Chemistry of Isomünchnones and Thioisomünchnones, an Under-Utilized Class of Mesoionic Compounds. Synthesis. Revew, p.123- 141. Jan. 1994. PADWA, A.; BRODNEY, M. A.; MARINO JR, J. P.; OSTERHOUT, M. H. e PRICE, A. Tandem Dipolar Cycloaddition-Mannich Cyclization as na Approach to Tricyclic Nitrogen Heterocycles. J. Org. Chem. v. 62, p. 62-67. 1997. PADWA, A. 1,3-dipolar cycloadition Chemistry. New York: Wiley-Intercience publication. 1984. vol. 1. PATRICK, G. L. An Introduction to Medicinal Chemistry. New York: Oxford University Press, p. 9-14. 1995. POTTS, K. T.; HOUGHTON, E. e SINGH, U. P. Mesoionic Compounds. XXXI. The Preparation and Cycloaddition Reactions of The Anhydro-4- hydroxythiazolium Hydroxide System With Acetylenic Dipolarophiles. J. Org. Chem. v. 39, n. 25, p.3627. 1974. REKKER, R. & DEKORT, H. Eu. J. Med. Chem. v. 14, p. 47. 1979. SAKAI, N.; FUNABASHI, M.; HAMADA, T.; MINAKATA, S.; RYU, I. E KOMATSU, M. Synthesis of Mesomeric Betaines Containing a Pyrroloor Imidazotriaziniumolate System and Their Cycloaddition with Acetylenic Dipolarophiles Leading to Triazocinone Derivatives. Tetrahedron . v. 55, p.13703-13724. 1999. SCHÖNBERG, A. J. Chem. Soc., 824. 1938. SPONHOLTZ III, W. R.; TRUJILLO, H. A. e GRIBBLE, G. W. Tandem 1,3-dipolar Cycloaddition of Mesoionic 2,4-Diphenyl-1,3-oxathiolium-5-olate With Cycloocta-1,5-diene. A New Synthesis of the Tetracyclo[6.2.0.04,10.05,9]decane ring system. Tetrahedron Lett. v. 41, p. 1687-1690. 2000. 88 SANTOS, D. F.; MACIEL, M. A. M.; ECHEVARIA, A.; SARTI, S. J. e CARVALHO, J. C. T. Estudo da Ação Antiinflamatória e Potência Ulcerogênica de Compostos Mesoiônicos, 1,4-Difeniltiossemicarbazida e Derivados. Revista Brasileira de Ciências Farmacêuticas, Brazilian Journal of Pharmaceutical Sciences. v. 36, n. 2, p. 292-299. 2000. SILVIA, M. S. C. C.; CARNIERI, E. G. S.; ECHEVARRIA, A. e OLIVEIRA, M. B. M., Effect of MI-D, A New Mesoionic Compound, on Energy-Linked Functions of Rat Liver Mitochondria. FEBS Lett. v. 440, p. 46-50. 1998. SOLIS, P. N.; WRIGHT, C. W.; ANDERSON, M. M.; GUPTA, M. P. e PHILLIPSON, J. D., Planta Medica. v. 59, p. 250-252. 1992. STOTHERS, J. B. Carbon-13 NMR Spectroscopy: A Series of Monographs. A. T. Blonquist & H. Wasserman (eds). New York: Academic Press, v. 24, Chapter 7. 1972. SUSTMANN, R., A Simple Model For Substituent Effects In Cycloaddition Reactions. I. 1,3-Dipolar Cycloaddition. Tetrahedron Lett. v. 29, p. 2717-2720. 1971. WERMUTH, C. G. Molecular Variations in Homologous Series: Vinylogues and Benzologues. In: The Practice of Medicinal Chemistry. New York: Academic Press Ltd. p.181 – 201. 1996. VOGUEL, A. I. Vogel’s Textebook of Pratical Organic Chemistry, 5th. Edition. London: Logman Group-UK Ltd. p. 720-723. 1989.por
dc.subject.cnpqQuímicapor
dc.thumbnail.urlhttps://tede.ufrrj.br/retrieve/63677/2004%20-%20Paulo%20Afonso%20de%20Almeida.pdf.jpg*
dc.originais.urihttps://tede.ufrrj.br/jspui/handle/jspui/4308
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