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| Author(s): |
Giovanni Wilson Amarante
Total Authors: 1
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| Document type: | Doctoral Thesis |
| Press: | Campinas, SP. |
| Institution: | Universidade Estadual de Campinas (UNICAMP). Instituto de Química |
| Defense date: | 2009-08-21 |
| Examining board members: |
Fernando Antonio Santos Coelho;
Peter Bakuzis;
Vitor Francisco Ferreira;
Luiz Carlos Dias;
Paulo Cesar Muniz de Lacerda Miranda
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| Advisor: | Fernando Antonio Santos Coelho |
| Abstract | |
This work explored the Morita-Baylis-Hillman (MBH) reaction. Mechanistic aspects are explored as well as the uses of its adducts as substrates for the synthesis of biologically active compounds. Using ESI-MS, we describe mechanistic studies of this reaction, intercepted and characterized intermediates under gas phase conditions. Using the same method, we re-evaluated the behavior of (thio)ureas as organocatalysts in the MBH reaction. In this work we propose a new mechanistic view for the role of (thio)ureas as Brønsted-acid catalysts in the MBH reaction. In the second part of this thesis, we used the MBH adducts to prepare substances with pharmaceutical properties. Thus, we synthesized a 4- fluorquinolone skeleton. As starting materials, we used MBH adducts from onitrobenzaldehyde. In particular, we studied one step of this synthesis, an intramolecular cyclization in presence of TFA. We used ESI-MS to intercept and characterize a new key intermediate for this reaction. After 4 steps, the antibiotic Norfloxacine was prepared. We also propose the enantioselective synthesis of DFP (5,5-dimethyl-3-(2- propoxy)-4-(4-methanesulfonylphenyl)-2-(5H)-furanone) analogues. We used a MBH adduct as a starting material, and after 3 steps we prepared an allylic alcohol derivative. This compound was then used in the asymmetric Sharpless epoxidation methodology. In the final steps, we used palladium to catalyze stereoselective ring opening and a sequential benzylic oxidation. After 2 steps, we concluded the synthesis of both enantiomers of the DFP analogues. In the last part of this work, we used the Curtius rearrangement on Morita- Baylis-Hillman adducts to prepare acyloins. They were treated with different types of amines to give diastereoselective 1,2-aminoalcohols. The first strategy was applied in the synthesis of the (+/-)-bupropion and the second was used in the diastereoselective synthesis of the (+/-)-spisulosine (AU) | |
| FAPESP's process: | 05/02373-2 - Synthesis of drugs and bioactive substances from Baylis-Hillman adducts: 1) synthesis of 4-fluoroquinolonic acid class antibiotics; 2) asymmetric synthesis of antiinflammatory DFP |
| Grantee: | Giovanni Wilson Amarante |
| Support Opportunities: | Scholarships in Brazil - Doctorate |