Synthetic studies on a novel celastrol- fluo-rescent probe for in vivo imaging and novel amination methodologies

• Autor(a) principal: Gonçalves, Carlos Rafael Costa
• Data de Publicação: 2017
• Tipo de documento: Dissertação
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10362/25873
• topic: Aminomethylation; Amine synthesis; Unactivated Alkenes; Flavylium coumpounds; synthesis of fluorescent compounds; celastrol; Domínio/Área Científica::Engenharia e Tecnologia::Engenharia Química

This dissertation was divided into two parts: Part 1 A novel methodology of aminomethylation of alkenes and alkynes was studied. The methodology developed involved the use of TFA to promote iminium formation from tetramethyldiaminomethane, which in turn reacts with a nucleophilic double bond to deliver an amine. A very well-rounded scope was accomplished with examples that range from aliphatic, cyclic and aromatic alkenes. Functional group tolerance was also pursuit with the method showing a great tolerance towards commonly used groups such as halides and esters. A total number of 25 boc-protected amines were synthesized using alkenes with yields up 82 %. Part 2 The second part consisted on the development of a fluorescence probe using a fla-vylium ion for in vivo imaging. In order to develop a fluorescent system that could be used in in vivo imaging for detection cancer cells, the prepared flavilyum was coupled with the theraupeutical relevant Celastrol. A new flavilyum ion was synthesized via condensation of a 7-diethylaminophenol with acetophenone possessing an halogenated alkylic linker at the 4’ position. Different pathways were investigated in order to reach and optimize the synthesis of a C4 functionalized flavylium salt that was prepared in three steps. Attempts were performed to couple the prepared flavylium to Celastrol.