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| Author(s): |
Ariane Fernandes Bertonha
Total Authors: 1
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| Document type: | Master's Dissertation |
| Press: | São Carlos. |
| Institution: | Universidade de São Paulo (USP). Instituto de Química de São Carlos (IQSC/BT) |
| Defense date: | 2014-02-21 |
| Examining board members: |
Antonio Carlos Bender Burtoloso;
Marcio Weber Paixão;
Alessandro Bolis Costa Simas
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| Advisor: | Antonio Carlos Bender Burtoloso |
| Abstract | |
The basic structure of indolizidine alkaloids is formed by a five and sixmembered bicyclic ring containing one nitrogen atom shared at the 4 position. This ring system has great prominence among the alkaloids, it is present in a large number of compounds and possess interesting biological profiles. Ipalbidine, for example, is an indolizidine alkaloid with analgesic and anti-oxidant properties. Although this compound has a relatively simple chemical structure, only four enantioselective synthesis are described for this compound. Thus, this dissertation aims to study a new synthetic strategy that allows the preparation of (+)-ipalbidine, as well as other alkaloids having the system 4- azabicyclo[4.3.0]non-3-ene with a phenolic substituent in position 3. A possible interesting route for the synthesis of these alkaloids is to obtain the indolizidine skeleton from a cyclization reaction using a functionalized α-chloroketone (derivative of protected (S)-prolinal (Boc and Cbz)). The key steps of this strategy are: an olefination reaction (Wittig), the preparation of α-chloroketones, addition of aryl group to the α-chloroketones and converting them into the indolizidine skeleton by a cyclization reaction. The α-chloroketones were prepared with overall yields varying from 56 % (Cbz) to 81% (Boc) starting from protected (S)-prolinal in just three steps: olefination reaction , followed by a reduction reaction of the obtained olefin and preparation of the α-chloroketone from an ester . The addition step of the aryl group to α-chloroketone was obtained for both Boc (40%) and Cbz (42%) groups. The Boc-protected α-chloroalcohol was converted to indolizidine skeleton through an \"one-pot\" deprotection reaction, followed by a cyclization reaction (80 %). The cyclization product, in turn, was converted to the novel (+)-ipalbidine analog, (S)-desoxyipalbidine (30 %). This strategy led to the synthesis of (S)-desoxyipalbidine in 6 steps and overall yield of 8 %. It is noteworthy that this type of approach using α-chloroketones was never employed in the synthesis of indolizidine alkaloids, and that strategy can be applied also to the total synthesis of (+)-ipalbidine and other indolizidine alkaloids such as phenanthroindolizidine. (AU) | |
| FAPESP's process: | 11/15903-0 - Studies Towards the Synthesis of Phenantroindolizidines |
| Grantee: | Ariane Fernandes Bertonha Delezuk |
| Support Opportunities: | Scholarships in Brazil - Master |