Dynamic Kinetic Resolution of amino acid derivatives, aiming at the synthesis of N-propargyl substituted compounds

• Grant number: 18/14154-3
• Support type: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): December 01, 2018
• Effective date (End): July 31, 2019
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Organic Chemistry
• Principal Investigator: Fernanda Amaral de Siqueira
• Grantee: Verônica Barros da Cunha
• Home Institution: Instituto de Ciências Ambientais, Químicas e Farmacêuticas (ICAQF). Universidade Federal de São Paulo (UNIFESP). Campus Diadema. Diadema , SP, Brazil

Abstract

He proposed project aims to synthesize amides derived from the N-substituted phenylglycine and phenylalanine amino acids with the propargyl group. The synthesis is based on four reaction steps: addition-elimination electrophilic substitution amidation; Dynamic kinetic resolution (DKR), with initial test of Palladium catalysts, performed in an alkaline medium and in a hydrogen atmosphere; followed by alkylation (insertion of the propargyl group); and finally, a hydrolysis reaction of the amide. The proposed synthesis is an unpublished route in the literature and aims to the formation of compounds that have inhibitory activity of the MAO-B enzyme present in the central nervous system, in which it is an important therapeutic target for disorders characterized by a decline in neurotransmission dopaminergic including Parkinson's disease (PD).