Studies towards the total synthesis of halichlorine and analogues

• Grant number: 06/02801-7
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Effective date (Start): September 01, 2006
• Effective date (End): January 31, 2008
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Organic Chemistry
• Principal Investigator: Ronaldo Aloise Pilli
• Grantee: Leonardo José Steil
• Host Institution: Instituto de Química (IQ). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

The marine alkaloids halichlorine, pinnaic acid and tauropinnaic acid, isolated by Uemura and co-workers in 1996, show the common 1-aza-[4.5.0]-spirobicyclic core. The biological activity of halichlorine is related to inhibit vascular cell adhesion molecule-1 (VCAM-1) at IC50 7 mg/mL. The pinnaic acid and tauropinnaic acid are phospholipase A2 (PLA2) inhibitors. Despite the structural similarity of halichlorine, pinnaic acid and tauropinnaic acid, the synthetic approach to these natural products show a commom intermediary compound, the 1-aza-[4.5.0]-spirobicyclodecane core. The work that was already developed until now by our research group, which aims the racemic total synthesis of these natural products, has as key-steps the Michael addition of a N-propyonylpyrrolydine enolate to an alpha,beta-insaturated ester and subsequent in situ alkylation, a Dieckmann condensation and Beckmann rearrangement. The key-steps to be developed in this project involve a metathesis reaction and a catalytic Nozaki-Hiyama-Kishi reaction for the three natural products, a macrolactonization for halichlorine and a peptidic coupling for tauropinnaic acid. (AU)