Dynamic metabolism in Piper gaudichaudianum: study of stereoselectivity of gaudichaudianic acid cyclization steps

• Grant number: 11/16823-0
• Support type: Scholarships in Brazil - Master
• Effective date (Start): March 01, 2012
• Effective date (End): January 31, 2014
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Organic Chemistry
• Principal Investigator: Maysa Furlan
• Grantee: Amanda Uliana de Carvalho
• Home Institution: Instituto de Química (IQ). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil

Abstract

The family Piperaceae comprises about 4000 species, many of which are used in traditional medicine to treat various diseases. The biological potential of this family is due to the accumulation of different classes of secondary metabolites, among which stand out prenylated derivatives of p-hydroxybenzoic acid. The portion of isoprene present in these compounds is considered a potent pharmacophore group, which enhances the intrinsic bioactivity of these compounds. The species Piper gaudichaudianum in particular, presents in its constitution the 2-methyl-2-(4'-methyl-3'-pentenyl)-8-(3''-methyl-2''-butenyl)-2H-1-chromene-6-carboxylic acid, known as gaudichaudianic acid, a prenylated chromene, in addition to being the major constituent of the metabolites found in leaves and roots of this species, has known trypanocidal and antifungal activity against phytopathogens. Chemical studies showed the rare presence of two natural isomeric forms (+)-S and (-)-R-gaudichaudianic acid during the isolation of the compound, encouraging further interest in the evaluation of such metabolite biosynthetic steps. It is proposed that during the cyclization step and formation of the benzopyran nucleus can occur by enzymatic catalysis (enzyme cyclase), post-biosynthetic racemization or racemization during the isolation and purification processes. Based on this background, this project aims to study the metabolic pathways involved in the biosynthesis of this class of compound in order to evaluate the occurrence of racemization, and to verify the antifungal activity of each enantiomer and the racemic mixture against human pathogens.