Full text
| |
| Author(s): |
Erica Cristina da Silva
Total Authors: 1
|
| Document type: | Doctoral Thesis |
| Press: | Campinas, SP. |
| Institution: | Universidade Estadual de Campinas (UNICAMP). Instituto de Química |
| Defense date: | 2017-08-04 |
| Examining board members: |
Fernando Antonio Santos Coelho;
Nelson Luís de Campos Domingues;
Sergio Pinheiro;
Cátia Ornelas;
José Augusto Rosário Rodrigues
|
| Advisor: | Fernando Antonio Santos Coelho |
| Abstract | |
Polyhydroxylated pyrrolidines and piperidines present a range of biological activities and can be used as prototypes for the design of new drugs for the treatment of diabetes, cancer, viral infections, etc. In the first part of this work we performed a study aimed at the synthesis of pyrrolidines from a Morita-Baylis-Hillman (MBH) adduct. An advanced intermediate was prepared in six steps in an overall yield of 16%. In the second part of this work we describe the asymmetric synthesis of LAB-1, a polyhydroxylated pyrrolidine exhibiting potent ?-glycosidase inhibitory activity. In addition to being a potent agent for combating HIV replication. The synthesis was performed in six steps, with an overall yield of 12%. This is the first report of total asymmetric synthesis of a polyhydroxylated pyrrolidine from Morita-Baylis-Hillman adducts. Studies aiming to obtain derivatives of this pyrrolidine were also performed without success. In the third part of this work, we performed studies aimed at the synthesis of polyhydroxylated piperidines, however, problems related to the displacement of an aldehyde-hydrate balance, made it impossible to use the initially proposed route. We changed the synthetic route for the formation of a new aldehyde that would be used with substrate for an MBH reaction, however in the penultimate stage, a 1.4 migration of the silyl group occurred, making the sequence unviable. Alterations in the protecting groups led us to the synthesis of benzylated alcohol, an intermediate which may lead to the formation of the desired aldehyde and the completion of piperidine synthesis (AU) | |
| FAPESP's process: | 13/06757-6 - Synthesis and biological evaluation of functionalized pyrrolidines and piperidines having potential inhibitory activity against alpha-glycosidase, from Morita-Baylis-Hillman adducts |
| Grantee: | Érica Cristina da Silva |
| Support Opportunities: | Scholarships in Brazil - Doctorate |