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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
1

Síntesi de base sòlida de pèptids biarílics contenint 5-arilhistidines

Cerezo Frias, Vanessa 28 May 2009 (has links)
Els aminoàcids biarílics es troben en una àmplia varietat de pèptids naturals amb important activitat biològica. Concretament, les arilhistidines formen part de les aciculitines, pèptids amb activitat citotòxica i antifúngica, La reacció de Suzuki-Miyaura és el mètode més versàtil per obtenir biarils assimètrics, encara que, fins el moment, no s'havia aplicat per a l'arilació de l'imidazole de la histidina. L'objectiu general d'aquesta tesi fou demostrar que es podia arilar l'imidazole de la histidina en fase sòlida mitjançant una reacció de Suzuki-Miyaura. En primer lloc, es sintetitzaren 4(5)-metil-5(4)-fenilimidazole i 4(5)-metil-5(4)-(2-metoxifenil)imidazole a través de l'acoblament creuat entre un N-benzilbromoimidazole i el corresponent àcid arilborònic. Posteriorment, s'arilaren 5-bromohistidines utilitzant diversos àcids arilborònics mitjançant una reacció de Suzuki-Miyaura assistida per irradiació micrones, tant en dissolució com en fase sòlida. I finalment, mitjançant aquesta metodología, es sintetitzaren pèptids antimicrobians contenint 5-arilhistidines actius contra bacteris gram-negatius responsables d'importants malalties en plantes com el foc bacterià. / Biaryl amino acids are present in a great variety of natural peptides which display important biological activities. In particular, arylhistidines naturally occur in cytotoxic and antifungal marine peptides, aciculitins. The Suzuki-Miyaura cross-coupling is the most versatile method to obtain unsymmetrical biaryls. Up to now, it had not been applied to the arylation of the histidine imidazole ring. The main objective of this thesis was to demonstrate that a Suzuki-Miyaura reaction was amenable to solid-phase arylation of the histidine imidazole ring. Firstly, it was synthesized 4(5)-methyl-5(4)-phenylimidazole and 4(5)-methyl-5(4)-(2-methoxyphenyl)imidazole by cross-coupling between N-benzylbromoimidazole and the corresponding arylboronic acid. Secondly, 5-bromohistidines were arylated with several arylboronic acids by a microwave-assisted Suzuki-Miyaura cross-coupling reaction in solution as well as solid-phase leading to the corresponding arylhistidines. Finally, antimicrobial peptides containing 5-arylhistidines were prepared using the previous methodology. They showed activity against gram-negative bacteria responsible of important plant diseases such as fire blight.

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