Isolation of 3??-acetoxy-copalic and 3??-hydroxy-copalic from the non-volatile fraction of copaiba oil-resin (Copaifera L. spp. - Fabaceae) and semisynthesis of derivatives

Autor: Negreiros, Ronei de Souza, https://orcid.org/0000-0001-5350-9204
Přispěvatelé: Pohlit, Adrian Martin, Lopes, Edizon Veiga, Novais, Alisson Meza, Passo, Joel Aparecido
Jazyk: portugalština
Rok vydání: 2022
Předmět:
Zdroj: Biblioteca Digital de Teses e Dissertações da UFAM
Universidade Federal do Amazonas (UFAM)
instacron:UFAM
Popis: Submitted by Ronei de Souza Negreiros (roneidesouzanegreiros@gmail.com) on 2022-12-07T16:23:01Z No. of bitstreams: 2 CartaEncaminhamento DISSERTA????O.pdf: 110196 bytes, checksum: 294253c5601a5ecefbb8904631a8c2cf (MD5) Disserta????o Ronei Negreiros-Dep??sito.pdf: 8026559 bytes, checksum: 2589f978d9464142935c643f0bcb8dfc (MD5) Approved for entry into archive by PPGQ Qu??mica (ppgqsecretaria@gmail.com) on 2022-12-07T17:14:29Z (GMT) No. of bitstreams: 2 CartaEncaminhamento DISSERTA????O.pdf: 110196 bytes, checksum: 294253c5601a5ecefbb8904631a8c2cf (MD5) Disserta????o Ronei Negreiros-Dep??sito.pdf: 8026559 bytes, checksum: 2589f978d9464142935c643f0bcb8dfc (MD5) Approved for entry into archive by Divis??o de Documenta????o/BC Biblioteca Central (ddbc@ufam.edu.br) on 2022-12-21T15:18:55Z (GMT) No. of bitstreams: 2 CartaEncaminhamento DISSERTA????O.pdf: 110196 bytes, checksum: 294253c5601a5ecefbb8904631a8c2cf (MD5) Disserta????o Ronei Negreiros-Dep??sito.pdf: 8026559 bytes, checksum: 2589f978d9464142935c643f0bcb8dfc (MD5) Made available in DSpace on 2022-12-21T15:18:55Z (GMT). No. of bitstreams: 2 CartaEncaminhamento DISSERTA????O.pdf: 110196 bytes, checksum: 294253c5601a5ecefbb8904631a8c2cf (MD5) Disserta????o Ronei Negreiros-Dep??sito.pdf: 8026559 bytes, checksum: 2589f978d9464142935c643f0bcb8dfc (MD5) Previous issue date: 2022-07-15 CNPq - Conselho Nacional de Desenvolvimento Cient??fico e Tecnol??gico Copaibeiras are well known in the Amazon region for arousing much interest among researchers, mainly due to the biological properties of the oil-resin of this plant. The oil resin is extracted from the trunk. It consists mainly of sesquiterpenes and diterpenes. Sesquiterpenes predominate in the volatile fraction or essential oil while diterpenes are the main chemical constituents of the fixed fraction or resin. Essential oil is used by the cosmetic industry as a raw material for various products. Its separation from the oil-resin takes place through distillation processes. The latter generate a residual non-volatile fraction that is rich in diterpenes. The present work has as its main objectives to perform an extensive survey of literature on the chemical composition and biological activity of Copaifera spp., to isolate substances from the residual, non-volatile fraction of copaiba oleoresin obtained after commercial distillation and to prepare semi-synthetic derivatives of isolated substances (thru straight-forward chemical reactions such as acylation or hydrolysis). Two diterpenes were isolated from the non-volatile fraction of copaiba oleoresin using sequential normal phase column chromatographies followed by RP-HPLC and identified as 3??-hydroxycopalic and 3??-acetoxycopalic acids based on 1H and 13C NMR, DEPT 135, COSY, HSQC, HMBC, LC HRMS and optical rotation, as well as comparison with literature data. These two carboxylic acids are known by several names in the literature. Consistent with the structure and C-5 and C-10 absolute configurations established originally for copalic acid by Nakano e Djerassi these compounds are called 3??-substituted copalic acid derivatives. 3??-hydroxycopalic acid was obtained from isolated 3??-acetoxycopalic acid under hydrolysis conditions (10% KOH in 9:1 MeOH/H2O) in 76% yield. 3??-hydroxycopalic acid (from isolation) was subjected to acetylation (treatment with acetic anhydride in pyridine and DMAP) and butyrylation (treatment with butyric anhydride in pyridine and DMAP) reactions resulting in the formation of semi-synthetic products 3??-acetoxy-copalic and 3??-butanoyloxycopalic acids in 70 and 42%, respectively. The formation of the reaction products was confirmed based on their 1H NMR and LC-HRMS characteristics. Conformational analyses and multiplicities (J values) of the 1H signals corresponding to H-3 and H-5 were consistent with H-3, H-5 and angular CH3 (at C-10) relative configurations of ??, ?? and ??, respectively, with small distortion of the chair conformation in the A ring due to 1,3-diaxial repulsions among the CH3 substituents at C-4 and C-10 in isolates and reaction products. As copaibeiras s??o muito conhecidas na regi??o Amaz??nica por despertar muitas pesquisas, principalmente devido as propriedades biol??gicas que o ??leo-resina desse vegetal apresenta. A partir do tronco dessas plantas ?? extra??do o ??leo-resina. Esse ?? constitu??do principalmente de sesquiterpenos e diterpenos. Os sesquiterpenos s??o majorit??rios na fra????o vol??til, conhecida como ??leo essencial. Enquanto os diterpenos s??o os principais constituintes qu??micos da parte fixa, classificada como resina. O ??leo essencial tem sido usado pela ind??stria cosm??tica como mat??ria-prima de variados produtos. A sua separa????o do ??leo resina acontece por processo de destila????o. Este processo gera um res??duo denominado de fra????o n??o vol??til rico em ??cidos diterp??nicos. O presente trabalho teve como objetivos principais: fazer levantamento extensivo de dados sobre a composi????o qu??mica e atividade biol??gica de Copaifera spp., isolar subst??ncias da fra????o n??o vol??til do ??leo-resina da copa??ba p??s-destila????o de origem comercial e submet??-las a rea????es qu??micas (hidr??lise ou acila????o). Dois diterpenos foram isolados da fra????o n??o vol??til utilizando cromatografia em coluna de fase normal sequencial seguido de CLAE-FR e identificados como os ??cidos 3?? hidr??xi-cop??lico e 3??-acet??xi-cop??lico baseado nos seus dados de RMN de 1H, 13C, DEPT 135, COSY, HSQC, HMBC, CL-EMAR, rota????o ??ptica, e compara????o com dados existentes na literatura. O ??cido 3??-hidr??xi-cop??lico foi obtido do ??cido 3??-acet??xi-cop??lico (proveniente de isolamento) em condi????es de hidr??lise (KOH 10% em MeOH/H2O 9:1) com 76% de rendimento. O ??cido 3??-hidr??xi-cop??lico (proveniente de isolamento) foi submetido ??s rea????es de acetila????o (tratamento com anidrido ac??tico em piridina e DMAP) e de butirila????o (tratamento com anidrido but??rico em piridina e DMAP), levando aos produtos semissint??ticos, os ??cidos 3??-acet??xi-cop??lico e 3??-butanoil??xi-cop??lico, com rendimentos de 70 e 42%, respectivamente. A forma????o dos produtos das rea????es foi confirmada baseado nas suas caracter??sticas de RMN de 1H e CL-EMAR. An??lises conformacionais e multiplicidades (valores de J) dos sinais correspondentes a H-3 e H-5 foram consistentes com as configura????es relativas dos H-3, H-5 e da CH3 angular (em C-10) como ??, ?? e ??, respectivamente, com pequena distor????o da conforma????o cadeira no anel A devido ?? repuls??o 1,3-diaxial entre as CH3 nas posi????es 4 e 10 para os isolados/produtos das rea????es.
Databáze: OpenAIRE
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