| spelling |
Gaspar Diaz Muñozhttp://lattes.cnpq.br/6284564771639521Ricardo José AlvesAntonio Jacinto DemunerLuciana Gonzaga de OliveiraAmanda Silva de Mirandahttp://lattes.cnpq.br/0915713698167414Suélen Karine Sartori2021-08-28T14:57:34Z2021-08-28T14:57:34Z2021-04-30http://hdl.handle.net/1843/37821Lactonas são ésteres cíclicos e seu grupo funcional está presente na estrutura de diversos produtos naturais. Elas são uma classe de compostos orgânicos de grande importância, devido às suas atividades biológicas, sendo seus principais expoentes as d-lactonas. Dentre essas, as d-lactonas a,b-insaturadas, também conhecidas como 5,6-di-hidro-2H-piran-2-onas, são as que mais se destacam. A (-)-cleistenolida (1), (-)-argentilactona (92) e (-)-massoialactona (93) são exemplos importantes dessa classe de compostos com marcantes atividades biológicas, tais como, antibacteriana e antifúngica. Diante disso, o presente trabalho teve como objetivo desenvolver uma nova rota sintética visando a obtenção dessas d-lactonas a,b-insaturadas, empregando o D-manitol, um poliol natural, como precursor quiral. Esses estudos estão relatados em dois capítulos: o primeiro aborda o desenvolvimento de rotas sintéticas para a obtenção de (-)-1, e o segundo as sínteses de (-)-92 e (+)-93, o enantiômero do produto natural. As sínteses dessas lactonas foram planejadas empregando o D-manitol como fonte dos centros estereogênicos presentes nessas moléculas. Os estudos envolvendo a síntese de (-)-1 levaram a obtenção de 27 compostos, dentre os quais, quinze são inéditos. A olefina Z 55, um intermediário-chave e inédito para síntese de (-)-1, foi obtida com 89% de rendimento empregando a reação de olefinação de Horner-Wadsworth-Emmons, modificada por Ando, a partir do aldeído 54 e o fosfonato 58. Essa olefina proporcionou a obtenção de 11 derivados sintéticos, dentre os quais, quatro são g-lactonas a,b-insaturadas inéditas 64, 70, 71 e 79, obtidas com rendimentos que variaram de 63 a 91%. A obtenção dessas é de grande valia, uma vez que os anéis g-lactônicos podem ser convertidos em anéis d-lactônicos. Além dessas, obteve-se também um produto inédito contendo anel furano proveniente da reação de adição 1,4 ao sistema carbonílico a,b-insaturado. Com os estudos realizados para a obtenção de (-)-92 e (+)-93 foram obtidos mais 14 compostos, dentre os quais, treze são inéditos. Dentre eles, as nitrilas 143 e 150 são intermediários sintéticos avançados para a síntese de (-)-92 e (+)-93 e foram obtidas com 75% de rendimento. Esses compostos foram obtidos a partir de suas respectivas olefinas 128 e 129, provenientes de reação de olefinação de Wittig entre o (R)-gliceraldeído cetal 34 e os sais de Wittig 130 e 131, empregando metodologia aprimorada durante o desenvolvimento desse trabalho.Lactones are cyclic esters that are found in the chemical structures of several natural products. It is a class of organic compounds of great importance due to its biological activities, their main exponent being the d-lactones. Among these, a,b-unsaturated d-lactones, also known as 5,6-dihydro-2H-pyran-2-ones, are the ones that stand out the most. The (-)-cleistenolide (1), (-)-argentilactone (92) and (-)-massoialactone (93) are important members of this class of compounds with marked biological activities, such as antibacterial and antifungal. In view of this, the present work aimed to develop a new synthetic route aiming at obtaining these a,b-unsaturated d-lactones, using D-mannitol, a natural polyol, as a synthetic precursor. These studies were distributed in two chapters: the first portrays the development of synthetic routes aiming at the synthesis of (-)-1, and the second for the syntheses of (-)-92 and (+)-93, the enantiomer of the natural product. The syntheses of these lactones were envisaged using D-mannitol as the source of the stereogenic centers present in these molecules. In studies involving the synthesis of (-)-1, twenty-seven compounds were obtained, of which 15 have not been described in the literature. Among these, olefin Z 55, a key and unprecedented intermediary for the synthesis of (-)-1, obtained with 89% yield using Horner-Wadsworth-Emmons olefination reaction, modified by Ando, from aldehyde 54 and phosphonate 58. With this olefin, it was possible to prepare 11 synthetic derivatives, four of them (compounds 64, 70, 71 and 79) are a,b-unsaturated g-lactones that have not been previsouly reported and they were obtained with yields ranging from 63 to 91%. Obtaining these is of great value, since g-lactonic rings can be converted into d-lactonic rings. In addition to these, one unpublished, product containing furan ring was obtained from 1,4-addition reaction to the a,b-unsaturated carbonyl system. With the studies carried out to obtain (-)-92 and (+)-93, more 14 compounds were obtained, among which, thirteen are unpublished. Among them, nitriles 143 and 150 are advanced synthetic intermediates for the synthesis of (-)-92 and (+)-93 and were obtained with 75% yield. These products were obtained from their respective olefins 128 and 129, from Wittig's olefin reaction between (R)-glyceraldehyde ketal 34 and Wittig's salts 130 and 131, using improved methodology during the development of this work.CNPq - Conselho Nacional de Desenvolvimento Científico e TecnológicoporUniversidade Federal de Minas GeraisPrograma de Pós-Graduação em QuímicaUFMGBrasilICX - DEPARTAMENTO DE QUÍMICAQuímica orgânicaLactonasCompostos orgânicos SíntesePolióisProdutos naturaisOlefinasNitrilasCompostos bioativos5,6-Di-hidropiran-2-onasD-ManitolReação de WittigReação de Horner-Wadsworth-Emmons5,6-Dihydropyran-2-onesD-MannitolWittig reactionHorner-Wadsworth-Emmons reactionEstudos visando a síntese estereosseletiva de derivados de piran-2-onas com marcantes atividades biológicasStudies aiming at the stereoselective synthesis of piran-2-one derivatives with remarkable biological activitiesinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFMGinstname:Universidade Federal de Minas Gerais (UFMG)instacron:UFMGORIGINALTese ppg Suélen Karine Sartori.pdfTese ppg Suélen Karine Sartori.pdfarquivo da tese de doutorado de Suélen Karine Sartoriapplication/pdf7403350https://repositorio.ufmg.br/bitstream/1843/37821/1/Tese%20ppg%20Su%c3%a9len%20Karine%20Sartori.pdf9e45785327f01a792e0de4665a55b27fMD51LICENSElicense.txtlicense.txttext/plain; charset=utf-82118https://repositorio.ufmg.br/bitstream/1843/37821/2/license.txtcda590c95a0b51b4d15f60c9642ca272MD521843/378212021-08-28 11:57:34.602oai:repositorio.ufmg.br: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ório InstitucionalPUBhttps://repositorio.ufmg.br/oaiopendoar:2021-08-28T14:57:34Repositório Institucional da UFMG - Universidade Federal de Minas Gerais (UFMG)false
|