Asymmetric Organocatalysis in the Synthesis of New Artemisin Analogues

• Grant number: 24/07893-5
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: June 01, 2024
• End date: February 29, 2028
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Organic Chemistry
• Principal Investigator: Bruno Matos Paz
• Grantee: Natan de Moura Uchiyama
• Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 22/14310-0 - Linear free energy relationships in asymmetric catalysis, AP.JP

Abstract

In this project, the synthetic preparation of a chemotheque of artemisinin analogues is proposed, in order to evaluate its efficacy to treat malaria, especially in resistant strains. In addition, the potential application in tumor cells will be studied with the main focus on verifying if there is cell death by ferroptosis. These syntheses will be guided by two main scopes: a pathway to Michael's adducts obtaining analogues with differences in lacton ring connectivity and, mainly, containing the ozonide group as a possible pharmacophore group; the other via cycloaddition of silyl-ketene-bis-vinylic acetals in order to obtain analogues with the common artemisinin connections. Both scopes will have organocatalyzed steps to study enantioselectivity and perform studies of linear free energy relationships.