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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Diastereoselective Synthesis of Biologically Active Cyclopenta[b]indoles

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Autor(es):
Santos, Marilia S. ; Fernandes, Daniara C. ; Rodrigues, Jr., Manoel T. ; Regiani, Thais ; Andricopulo, Adriano D. ; Ruiz, Ana Lucia T. G. ; Vendramini-Costa, Debora B. ; de Carvalho, Joao E. ; Eberlin, Marcos N. ; Coelho, Fernando
Número total de Autores: 10
Tipo de documento: Artigo Científico
Fonte: Journal of Organic Chemistry; v. 81, n. 15, p. 6626-6639, AUG 5 2016.
Citações Web of Science: 11
Resumo

The cyclopenta{[}b]indole motif is present in several natural and synthetic biologically active compounds, being directly responsible for the biological effects some of them present. We described herein a three step sequence for the synthesis of cyclopenta{[}b]indoles with a great structural diversity. The method is based on an oxidative Michael addition of suitable indoles on the double bond of Morita-Baylis-Hillman adducts mediated by a hypervalent iodine reagent (IBX) to form beta-ketoesters, which were chemoselectively reduced with NaBH4 in THE to give the corresponding beta-hydroxyesters. The diastereoisomeric mixture was then treated with a catalytic amount of triflic acid (20 mol %) to give cyclopenta{[}b]indoles with overall yields ranging from 8 to 73% (for 2 steps). The acid-catalyzed cyclization step gave the required heterocycles via an intramolecular Friedel Crafts reaction, with high diastereoselectivity, where only the trans product was observed. A mechanistic study monitored by ESI-(+)-MS was also conducted to collect evidence about the mechanism of this reaction. The new molecules herein synthesized were also evaluated against a panel of human cancer cells demonstrating a promising antiturnoral profile. (AU)

Processo FAPESP: 13/10449-5 - Adutos de Morita-Baylis-Hillman como blocos de contrução eficientes para a síntese de moléculas de interesse biológico
Beneficiário:Fernando Antonio Santos Coelho
Linha de fomento: Auxílio à Pesquisa - Regular
Processo FAPESP: 13/07600-3 - CIBFar - Centro de Inovação em Biodiversidade e Fármacos
Beneficiário:Glaucius Oliva
Linha de fomento: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
Processo FAPESP: 10/04716-2 - Aplicações sintéticas de adutos de Morita-Baylis-Hillman: nova abordagem para a síntese de compostos tricarbonílicos vicinais
Beneficiário:Marília Simão dos Santos
Linha de fomento: Bolsas no Brasil - Mestrado