Tesis doctoral de Sonia Flores Penalba
Synthesis and biological evaluation of new fluorinated imidazoline and ethanolamine-type derivatives one of the main goals of organic chemistry is the search of new compounds with interesting biological activity. Nitrogenated compounds embrace most of the biomolecules and are very attractive due to their important role in many metabolic and structural processes. Introduction of fluorine atoms in organic compounds often lead to products with an improved pharmacokinetic and pharmacodynamic profile. Considering this statements, the main objective of this work is the synthesis of new fluorinated nitrogen-containing molecules with a potential biological application and the evaluation of their in vitro activity. in chapter 1, a new methodology for the synthesis of ¿-fluorinated allylic amines through alquilation of imines with 2-trimethylsilylethyl sulfones, as vinyl anion equivalentes, followed by íY-elimination, has been developed. This methodology has been applied to the asymmetric version, using chiral 2-trimethylsilylethyl substituted sulfoxides. In this case, a tandem addition-íY-elimination process provided the corresponding allylic amines, altought with low enantioselectivity. The tandem addition-íY-elimination process has been extended to the synthesis of racemic fluorinated quaternary aminoacid derivatives with an allylic amine moiety. the first achievement of chapter 2 has been the utilization of chiral sulfinimines as starting materials for the preparation of chiral fluorinated allylic amines holding a 1,1-difluoro-1-phenyl substituent, with good yields and diastereoselectivity. Functional modification of the aforementioned chiral allylic amines has led to a series of difluorophenylmethylated analogues of íY-secretase inhibitors with a central 1,3-diamino-4,4-difluoro-4-phenyl-2-butanol core, that have been submitted to biological evaluation. A family of fluorinated and non-fluorinated ethanolamines have been evaluated as antimicrobial agents, showing a noteworthy selective inhibitory activity of the growth of mycobacterium and nocardia species. in the third chapter, the preparation of fluorinated and non-fluorinated 2-imidazolines bearing an olefinic chain has been achieved by reaction of ethyl esters derived from 2,2-difluoro-4-phenyl-3-butenoic acid, 2,2-difluoro-4-pentenoic acid and 4-pentenoic acid with comercially available diamines in the presence of trimethylaluminium as catalyst. Subsequent n-allylation in barbier conditions led to dienic systems suitable for cyclisation. Dienic imidazolines afforded, after ring-closing metathesis reaction, the corresponding bi(tri)cyclic amidines. The fluorinated and non-fluorinated products with 3,5,8,9-tetrahydro-2h-imidazo[1,2-a]azepine backbone were isolated with high yield while the synthesis of the imidazo[1,2-a]pyridine-pattern was not as favourable.
Datos académicos de la tesis doctoral «Síntesis y evaluación biológica de nuevos derivados de tipo imidazolina y etanolamina fluorados«
- Título de la tesis: Síntesis y evaluación biológica de nuevos derivados de tipo imidazolina y etanolamina fluorados
- Autor: Sonia Flores Penalba
- Universidad: Universitat de valéncia (estudi general)
- Fecha de lectura de la tesis: 10/03/2011
Dirección y tribunal
- Director de la tesis
- Santos Fustero Lardiés
- Tribunal
- Presidente del tribunal: María dolores Badia urrestarazu
- josefa Florez gonzalez (vocal)
- noureddine Khiar el wahabi (vocal)
- michael h. Cynamon (vocal)