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| Author(s): |
Gilmar Araújo Brito Júnior
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: | 2014-12-12 |
| Examining board members: |
Ronaldo Aloise Pilli;
Silvio do Desterro Cunha;
Diogo Sibert Lüdtke;
Igor Dias Jurberg;
Luciana Gonzaga de Oliveira
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| Advisor: | Ronaldo Aloise Pilli |
| Abstract | |
The Stemona alkaloids are a group of about 170 substances that possess unique structural features. Among those compounds, Parviestemoamide (11a/11b) was isolated in 1991, but its tridimensional structure was not elucidated. Through previous studies in our research group, a possible epimer of the proposed structure 11b was synthetized, but the spectroscopic analysis did not match with the reported data, preventing an unambiguous structural elucidation of this compound. Several synthetic approaches toward the 10 membered lactam in 48, 52 and 57 were tested, but the desired products were never obtained in any condition tested. A alternative synthetic strategy to initially prepare the 10 membered ring and then the 5 membered lactone was planned. In this way, compound 92 was prepared by the radical cyclization reaction, already having all the carbon atoms present in the proposed structure 11a/11b, but unfortunately it was not possible to conduct the double bond functionalization in this bicyclic compound using the tested methodologies. Employing computational tools and by comparative analysis with the natural product Stemoamide (17), we suggest that the natural product isolated by Xu and coworkers is Stemoamide (17) itself or an isomer of 17. On the other hand, Stemoamide (17) already has had its tridimensional structure elucidated through syntheses by many research groups. The hydrogenolysis followed by cascade cyclization on intermediate 51a led to the core 96b present in 9a-epi-Estemoamida (98) and its 9a epimer in a 5:1 ratio, respectively. Inspired by this result, we sought a condition that could provide the other diastereomer, 96a, present in the natural Stemona alkaloid, Stemoamide (17). Based on this, the intermediate 51b was submitted to a similar condition, with 10 atm of H2 pressure and trifluoroethanol as solvent. In this way, the desired isomer 96a was obtained with 10:1 diastereoisomeric ratio. Computational calculations have been employed to explain this facial selectivity. The conversion of compounds 96a and 96b in the alkaloids (±)-Stemoamide (17) and (±)-9a-epi-Stemoamide (98) is already reported in the literature, so we could perform a short and efficient synthesis of these alkaloids (AU) | |
| FAPESP's process: | 10/00219-4 - Asymmetric synthesis and structural determination of (-)-parviestemoamide. |
| Grantee: | Gilmar Araujo Brito Junior |
| Support Opportunities: | Scholarships in Brazil - Doctorate |