New synthetic asymmetric methodologies for the synthesis of bioactive building blocks and potential scale up/out

• Author(s): Gomes, Rafael
• Date: 2019
• Persistent ID: http://hdl.handle.net/10451/42269
• Origin: Repositório da Universidade de Lisboa
• Subject(s): Sustainability; Furfurals; Cyclopentenones; Continuous Flow Chemistry; Medicinal Chemistry
• Document Type: Doctoral thesis
• Language: English
• Contributor(s): Repositório Científico de Acesso Aberto da ULisboa; Afonso, Carlos Alberto Mateus; Mendonça, Ricardo Filipe de Jesus Gonçalves

Description

Preparation of medicinal relevant small molecules from biomass is a field of interest due to 1) structural diversity obtained in biomass modification, 2) being sustainable and an environmentally friendly approach, 3) low cost of starting materials most likely lead to low cost of final product. Amoungst biomass, the furans have been given special attention by the scientific community, namely furfural and 5-hydroxymethylfurfural (HMF). They can be obtained by de dehydration of non-edible carbohydrates and have been described as key building blocks for the future. On the other hand, cyclopentenones (CP) are a class of molecules that has used for medicinal purposes. The transformation of furfural to trans-4,5-diamino-cyclopent-2-enones or other CP derivatives has been reported by several different methodologies being available. However there has been no attempts on taking advantage of this sustainable transformation towards the development of new bioactive molecules. Also, although the transformation of furfural, Meldrum’s acid activated furfural and furyl alcohols to cyclopentenones has been studied, the same transformation using HMF has yet to be succeeded. In this thesis we studied the transformation of furans to CP, taking into consideration sustentability and possible scale up/out, and evaluate their biological activity. We observed that diferent families of CP prepared from furfural have remarkable anticancer and antibacterial activity, while CP prepared from HMF present antimalarial activity. The issue on HMF stability is also address during the course of this thesis, as well as the formation of aminals. The formation of aminals was used as means to protect furfural but was explored as a common protective group of aldehydes, as a way to scavenge genotoxic impurities and as a stimuli-responsive dynamic linker.