Total synthesis and evaluation of the cytotoxicity of cyclic depsipeptides Kohamamides A, B and C

• Grant number: 17/24294-4
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: January 01, 2018
• End date: December 31, 2018
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Organic Chemistry
• Principal Investigator: Júlio Cezar Pastre
• Grantee: Gabriel Aparecido Miranda e Silva
• Host Institution: Instituto de Química (IQ). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 14/26378-2 - Development of methodologies and synthetic processes employing a new technological platform: micro and meso reactor assisted synthesis of natural products and derivatives with potential pharmacological activity, AP.JP

Abstract

This project proposes the total synthesis of the cyclic depsipeptides kohamamides A, B and C, which belong to the kulolide super family, and are characterized for having a ²-hydroxyoctanoic acid derivate with a well defined sequence of aminoacid or hydroxyacid residues. These compounds present pharmacological potential, and some depsipeptides are currently on clinical trials. In this context, synthesis of novel kohamamides are highly desirable, and it may contribute to the development of new antitumour agents. The synthetic plan consists in a total of 15 steps, being 10 steps the longest linear sequence, that includes classical transformations to generate amides and esters, addition/remotion of protecting groups, and functional groups manipulation. After conclusion of kohamamides A, B and C syntheses, we propose the evaluation of the cytotoxic activity in vitro. (AU)