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Doctoral Thesis
DOI
10.11606/T.46.2006.tde-28032007-172228
Document
Author
Full name
Erika Rocha da Silva Gonçalo
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2006
Supervisor
Committee
Ferraz, Helena Maria Carvalho (President)
Bakuzis, Peter
Correia, Carlos Roque Duarte
Pardini, Vera Lúcia
Petragnani, Nicola
Title in Portuguese
bβ-enamino ésteres como precursores de análogos do GABA e de di-hidropiridinas
Keywords in Portuguese
Di-hidropiridinas
Enamino ésteres
GABA
Iodociclização
Abstract in Portuguese
Nesta tese foi empregada a iodociclofuncionalização de β-enamino ésteres para obtenção de análogos conformacionalmente restritos do ácido γ-aminobutírico (GABA) e de 4-aril-1,4-di-hidropiridinas (DHP's). Foram preparados ciclopentanos trissubstituídos a partir de b-enamino ésteres cíclicos, com o objetivo de investigar o mecanismo desta reação. Utilizando ESI(+)-MS/MS, foi possível identificar e caracterizar os intermediários bicíclicos catiônicos, confirmando que a reação se processa através de uma SN2 intramolecular. A biorredução do grupo acetila existente nos ciclopentanos, utilizando raízes de Daucus carota e células íntegras de Aspergillus terreus CCT 3320 e Rhizopus oryzae CCT 4964, forneceu novos análogos oticamente ativos do GABA, com excelente enantiosseletividade. Também foram preparados iodo-β-enamino ésteres cíclicos de seis membros, contendo um grupo arila na posição 4 do anel tetra-hidropiridínico, cuja desidroiodação forneceu os respectivos derivados 1,4-di-hidropiridínicos.
Title in English
β-enamine esters as precursors of GABA and dihydropyridines analogues
Keywords in English
Dihydropyridines
Enamine esters
GABA
Iodocyclization
Abstract in English
This thesis presents a study of iodo-cyclization of β-enamino esters in order to obtain conformationally restricted analogues of γ-amino butiric acid (GABA) and of 1,4-dihydropyridines (DHP's). Trisubstituted cyclopentanes were obtained from iodo-β-enamino esters and the mechanism of their formation was proposed and corroborated by (+)-ESI-MS/MS through the interception and structural characterization of the key bicyclic iminium ion intermediates. Optically active GABA analogues have been prepared in high enantiomeric excesses (up to >99%) by bioreduction of the keto group in cyclopentane derivatives using whole fungal cells of Aspergillus terreus CCT 3320, Rhizopus oryzae CCT 4964 and Daucus carota root. 4-aryl-1,4,5,6-tetrahydropyridine derivatives were synthesized by iodo-cyclization of a-alkenyl-b-enamino esters and 4-phenyl-1,4-dihydropyridine derivatives were obtained after base-promoted dehydroiodination of the corresponding cyclic iodo-b-enamino esters.
 
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tese1.pdf (2.43 Mbytes)
Publishing Date
2007-04-13
 
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