Directed functionalization of indolizines derived from propargylic alcohols aiming the synthesis of bioactive substances

• Grant number: 13/15375-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): September 01, 2013
• Effective date (End): August 31, 2014
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Organic Chemistry
• Principal Investigator: Giuliano Cesar Clososki
• Grantee: Camila Rodrigues de Souza Bertallo
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Despite organometallic bases such as those derived from magnesium and lithium may already being applied on preparative scale functionalization of various aromatics and heterocyclic rings, thir reactivity toward important substrates have not been properly studied. This is the case of indolizines and analogs. Because of its importance, the preparation methods of optimizing the existing methtods and developing new one aiming the construction of functionalized Indolizines is of great interest. Thus, the main objective of this project is to develop a methodology to allow the functionalization of indolizines synthesized from propargylic alcohols using organometallic bases. The corresponding organometallic intermediates will be then transmetalated with ZnCl2 and submitted to Negishi cross-coupling reactions. Aiming to demonstrate the importance of synthetic methodologies developed, we intend to apply these in the synthesis and structural modification of bioactive Indolizines such as STA-5312.