Description du projet :
Recently, we have reported a facile manganese pentacarbonyl bromide catalyzed cyclopropanation of N-acetyl indole, with aryl diazoesters (Orglett, 2019, 21, 2025). Post publication of this work we got interested to explore the outcome of this reaction with nitrogen free indole or with indoles protected with electron donating group at the nitrogen. To our most surprise both the substrates afforded mixtures of C2/ C3 functionalized products with aryl diazoesters instead of the cyclopropanated expected products. Next, application of this reaction on tryptamine derivatives followed by further synthetic manipulation afforded two molecules containing azepino and spiropiperidino indole framework. These scaffolds are found in natural products Ibogamine, Koumine, Surugatoxin and etc who generally demonstrates antagonistic activity against G protein coupled receptors (GPCRs). GPCRs are implicated in brain related ailments. Based on our published report and aforementioned proof of concept study we herein propose an optimized metal or metal promoted photocatalyzed protocol to access regioselective C2 and C3 functionalized tryptamine and tryptophan with aryl diazoesters and their application in the synthesis of a DOS (Diversity Oriented Synthesis) library with structural framework inspired from natural products Ibogamine & Koumine. We intend to screen the library against a diverse set of GPCRs to investigate their extent of modulation against the receptors. It is extremely important to collaborate with the partner abroad in this project. Prof. Gremaud has vast experience in metal mediated C-C, C-N and C-O bond forming reactions which will be utilized in this project to identify the ideal reaction condition for the optimum regioselectivity.
Research team within HES-SO:
Gremaud Ludovic
Partenaires académiques: Subhabrata Sen, Shiv Nadar universitiy - New Dehli India
Durée du projet:
01.09.2020 - 31.03.2021
Montant global du projet: 25'000 CHF
Statut: Completed
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