Diastereoselective Synthesis of Biologically Active Cyclopenta[b]indoles
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- 作者：Marilia S. Santos ; Daniara C. Fernandes ; Manoel T. Rodrigues Jr. ; Thais Regiani ; Adriano D. Andricopulo ; Ana Lúcia T. G. Ruiz ; Débora B. Vendramini-Costa ; João E. de Carvalho ; Marcos N. Eberlin ; Fernando Coelho
- 刊名：Journal of Organic Chemistry
- 出版年：2016
- 出版时间：August 5, 2016
- 年：2016
- 卷：81
- 期：15
- 页码：6626-6639
- 全文大小：631K
- 年卷期：0
- ISSN：1520-6904
文摘
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 β-ketoesters, which were chemoselectively reduced with NaBH4 in THF to give the corresponding β-hydroxy-esters. 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 antitumoral profile.