Total synthesis of the 209F pumiliotoxin alkaloid via SmI2 mediated cascade reaction

• Grant number: 12/02367-6
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: June 05, 2012
• End date: December 04, 2012
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Organic Chemistry
• Principal Investigator: Antonio Carlos Bender Burtoloso
• Grantee: Vagner Dantas Pinho
• Supervisor: David John Procter
• Host Institution: Instituto de Química de São Carlos (IQSC). Universidade de São Paulo (USP). São Carlos , SP, Brazil
• Institution abroad: University of Manchester, England
• Associated to the scholarship: 08/09653-9 - Total syntheses of the cardiotonics pumiliotoxin 209 F and homopumiliotoxin 223 G, BP.DR

Abstract

Pumiliotoxins (indolizidine alkaloids), homopumiliotoxins (quinolizidine alkaloids) and their congeners are a class of compounds isolated from the skin of some frogs from the Dendrobatidae, Mantellidae, Bufonidae, e Myobatrachidae families, possessing interesting pharmacologic activities (cardiotonic activity in low concentrations). Because of the big number of compounds among these toxins (about 100), synthetic methodologies that provide the preparation of these compounds (as well as analogues) in great amounts and in a fast and efficient way using common intermediates, are very important for application in chemical-biology. Since its introduction in organic chemistry the scope of transformations induced by SmI2 quickly grew up due its versatility and its application in numerous total syntheses of complex molecules have been described. Among the transformations mediated by SmI2, the formation of carbon-carbon bonds (C-C) are specially interesting given its ability to aggregate high molecular complexity in a single step due to the capacity SmI2 has to promote cascade reactions. This project proposes the preparation of the indolizidine alkaloid pumiliotoxina 209 F using SmI2 reagent in a concise approach that will also easily obtainable analogues in a few steps. (AU)