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Master's Dissertation
DOI
https://doi.org/10.11606/D.9.2009.tde-18092009-153237
Document
Author
Full name
Giancarlo di Vaccari Botteselle
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2009
Supervisor
Committee
Stefani, Hélio Alexandre (President)
Ludtke, Diogo Seibert
Omori, Alvaro Takeo
Title in Portuguese
Síntese de 2-aril e 2,5-diarilfuranos funcionalizados: potenciais sondas fluorescentes
Keywords in Portuguese
2-Aril/2.5-diarilfuranos
Aminoácidos conjugados
Insumos farmacêuticos
Medicamento (Síntese)
Organotelúrio/Organoboro
Síntese orgânica
Sondas fluorescentes
Suzuki- Miyaura
Abstract in Portuguese
A utilização de sondas fluorescentes para marcação ou detecção de biomoléculas de interesse em processos biológicos distintos, vem recebendo grande atenção em pesquisas biomédicas, de análises clínicas e biologia celular. Em geral, estas sondas fluorescentes são constituídas por moléculas orgânicas pequenas, as quais apresentam características fluorescentes e capacidade de conjugar-se com estas biomoléculas. Desta forma, esta dissertação descreve inicialmente a síntese de compostos 2-aril ou 2,5- diarilfuranos e tiofenos (3, 5, 7 e 9a-i), a partir de espécies orgânicas de telúrio (1, 4, 6 e 8) e sais de ariltrifluoroboratos de potássio (2a-i), via reação de acoplamento cruzado tipo Suzuki-Miyaura, sob catálise de paládio [ver a figura no arquivo original]. Em seguida, descreve a síntese de um derivado 2,5-diarilfurano assimétrico, o 2-(3-aminofenil)-5-(4-metoxifenil)furano 11, o qual apresenta propriedades químicas e luminescentes adequadas para atuar como uma nova e promissora sonda fluorescente em processos de marcação ou detecção biológica. A síntese desta nova sonda, também chamada de 3-AFA (3-AnililFuranoAnisol), foi realizada a partir da reação de acoplamento cruzado tipo Suzuki-Miyaura, sob catálise de paládio, entre o ácido (3-aminofenil) borônico 5e e o 2- (butiltelanil)-5-(4-metoxifenil)furano 10 em 65 % de rendimento. Esta nova sonda 3-AFA 11 foi conjugada com uma série de L-aminoácidos 12a-l, a partir de uma reação de acoplamento peptídico para formação dos respectivos produtos 13a-l em rendimentos satisfatórios. Estes produtos conjugados 13a-l, apresentam potencial para marcação fluorescente de enzimas proteolíticas de interesse [ver a figura no arquivo original]. Adicionalmente, foram caracterizadas propriedades fotofísicas importantes desta nova sonda 3-AFA 11, entre as quais seus espectros eletrônicos de absorção e emissão de fluorescência, que obtiveram valores de λex a 320 nm e λem a 400 nm, respectivamente. Por fim, foi testado o potencial de acúmulo intracelular da sonda 3-AFA 11 em sistemas celulares tais como: eritrócitos infectados com Plasmodium chabaudi e amastigotas de Leishmania L. amazonensis, sendo possível observar em todos os casos a marcação fluorescente dos respectivos parasitas.
Title in English
Synthesis of functionalized 2-aryl and 2,5-diarylfurans: potential fluorescent probes
Keywords in English
2-Aryl/2.5-diarylfurans
Combined amino acids
Drug (Synthesis)
Fluorescent probes
Organic synthesis
Organotellurium/Organoboron
Pharmaceutical raw material
Suzuki- Miyaura
Abstract in English
The use of fluorescent probes for labeling or detection of biomolecules of interest in different biological processes, has received much attention in biomedical, clinical testing and cell biology research. In general, these fluorescent probes are composed of small organic molecules, which have fluorescent features and ability to combine with these biomolecules. Thus, this work initially describes the synthesis of 2-aryl or 2,5-diarylfurans and thiophenes (3, 5, 7 and 9a-i) from organic species of tellurium (1, 4, 6 and 8) and potassium organotrifluoroborate salts (2a-i) by palladium catalyzed Suzuki-Miyaura crosscoupling reaction [see the figure in the original file]. After describe the synthesis of a unsymmetrical 2,5-diarylfuran derivative, the 2-(3-aminophenyl)-5-(4-methoxyphenyl)furan 11, which presents chemical and luminescent properties appropriate to act as a promising new fluorescent probes in processes of marking or biological detection. The synthesis of this new probe, also called 3-AFA (3-AnilylFuranAnisole), was performed from palladium catalyzed Suzuki-Miyaura cross-coupling reaction, between (3- aminophenyl) boronic acid 5e and 2-(butyltellanyl)-5-(4-metoxyphenyl)furan 10 in 65 % yields. This new probe 3-AFA 11 was combined with a series of Lamino acids 12a-l from a peptidic coupling reaction to obtain their products 13a-l in satisfactory yield. These combined products 13a-l show a potential for fluorescent marking of proteolitic enzymes [see the figure in the original file]. Additionally, important photo physical properties of this new probe 3-AFA 11 were characterized. These include their electronic spectra of absorption and fluorescence emission, who obtained values of λex to 320 nm and λem to 400 nm, respectively. Finally, we tested the potential of probe 3-AFA 11 for intracellular accumulation in cellular systems such as: erythrocytes infected with Plasmodium chabaudi and amastigotes of Leishmania L. amazonensis, in all cases the fluorescent uptake cellular of their parasites can be observed.
 
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Publishing Date
2010-03-23
 
WARNING: The material described below relates to works resulting from this thesis or dissertation. The contents of these works are the author's responsibility.
  • ALVES, Diego, et al. Copper Catalyzed Cross-Coupling Reactions of Diaryl Ditellurides with Potassium Aryltrifluoroborate Salts. Journal of the Brazilian Chemical Society, 2009, vol. 20, p. 988-992.
  • Stefani, Hélio A., et al. Synthesis, anti-inflammatory activity and molecular docking studies of 2,5-diarylfuran amino acid derivatives [doi:10.1016/j.ejmech.2011.10.018]. European Journal of Medicinal Chemistry [online], 2012, vol. 47, p. 52-58.
  • VIEIRA, A. S., et al. Synthesis of potassium and tetra n-butylammonium 2-substituted-1,3- dithianotrifluoroborate salts and addition to chiral cyclic N-acyliminium ions. Tetrahedron (Oxford), 2008, vol. 64, p. 7234-7241.
  • ALVES, Diego, et al. Copper catalyzed cross-coupling reactions of diaryl ditellurides with potassium aryltrifluoroborate salts. In 13th Brazilian Meeting on Organic Synthesis, São Pedro, 2009. Copper catalyzed cross-coupling reactions of diaryl ditellurides with potassium aryltrifluoroborate salts., 2009. Resumo.
  • KEPPLER, A., et al. From Z-Vinylic Tellurides to E-Vinyl BF3K salts: Unexpected Isomerization of Double Bonds. In 12th Brazilian Meeting on Organic Synthesis, Itapema - SC, 2007. 12th Brazilian Meeting on Organic Synthesis.Tubarao - SC : Grafica Coan, 2007. Resumo.
  • STEFANI, H. A., et al. Synthesis and evaluation of anti-inflamatory activity of 2,5-diarylfuran amino acids. In 70th FIP World Congress of Pharmacy/Pharmceutical Sciences, Lisboa, 2010. Synthesis and evaluation of anti-inflamatory activity of 2,5-diarylfuran amino acids., 2010. Abstract.
  • STEFANI, H. A., et al. Synthesis of potassium and n-tetrabutylammonium 2-substituted-1,3-dithianotrifluoroborate salts and addition to chiral cyclic N-acyliminium íons. In XIII International Conference on Boron Chemistry (XIII IMEBORON), Platja d´Aro, 2008. Synthesis of potassium and n-tetrabutylammonium 2-substituted-1,3-dithianotrifluoroborate salts and addition to chiral cyclic N-acyliminium íons., 2008. Abstract.
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