Diverted approaches to the synthesis of indolizidine alkaloids

Author(s)

Vagner Dantas Pinho

• Document type: Doctoral Thesis
• Press: São Carlos.
• Institution: Universidade de São Paulo (USP). Instituto de Química de São Carlos (IQSC/BT)
• Defense date: 2013-07-19

Examining board members

Antonio Carlos Bender Burtoloso; Joao Valdir Comasseto; Luiz Carlos Dias; Kleber Thiago de Oliveira

• Advisor: Antonio Carlos Bender Burtoloso

Abstract

Herein were described three diverted oriented approaches for the construction of the bicyclic scaffold of indolizidines alkaloids, that figures between one of the most important classes of natural products. In the first approach, a new method to prepare α,β - unsaturated diazoketones was described using the Horner-Wadsworth-Emmons (HWE) reaction between diazophosphonate and aldehydes. The unsaturated diazoketones were used as powerful plataforms to construct the indolizidine carbocyclic scaffold, enploying the Wolff rearrangement as the key step. The second approach was the development of a reductive coupling between α-aminocarbonyl derivatives and methyl acrylate, mediate by SmI2, from this approach, the well-known advanced intermediate for the synthesis of (-)-pumiliotoxin 251D e of the (+/-)-epiquinamide was obtained in only two steps. The third approach uses the intermolecular Wittig/HWE reaction as the key step in the construction of a bicyclic intermediate containing an α,β -unsaturated moiety that could be used for a diverted oriented approach in the indolizidine alkaloids synthesis. (AU)

• FAPESP's process: 08/09653-9 - Total syntheses of the cardiotonics pumiliotoxin 209 F and homopumiliotoxin 223 G
• Grantee: Vagner Dantas Pinho
• Support Opportunities: Scholarships in Brazil - Doctorate