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Total Synthesis of Phlegmarine Alkaloids

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[eng] This doctoral thesis consists in two main parts. The first part focus in the study of methodology development in order to bring modularity and diversification to compounds studied within the research group. It consists first in the development of an easy procedure to access enantiopure substituted octahydroindoles relevant for natural products synthesis, then in the diversification of a common building block used for the total synthesis of phlegmarine alkaloids allowing access to unprecedented heterocyclic tetrahydrocarbazoles compounds, but most importantly in the achievement of a methodology allowing access to any phlegmarine alkaloids from a simple common precursor i.e. using a unified methodology. A stereodivergent hydrogenation route is reported in each phlegmarine alkaloid series, allowing modulation of the diastereoselectivity in key intermediates of the synthetic approach. The second part focuses on synthetic applications of the methodology developed to allow to perform the first total synthesis of various phlegmarine alkaloids and also shed light on missassigned structures. These structure reassignments gave birth to a revised classification of the phlegmarine alkaloids and were confirmed by total synthesis using the unified methodology developed in the first part. All of the analytical data obtained during this project led us to the establishment of general rules to determine easily the stereochemistry of any phlegmarine type alkaloids. In summary, the first total syntheses of (+)-serratezomine E, (-)-serralongamine, (-)-huperzine K, huperzine M and (-)-huperzine N have been achieved and the usefulness of the tandem intermolecular Michael reaction/intramolecular aldol reaction and in-situ intramolecular aza-Michael process has been extended to other series of azabicyclic compounds in enantiopure form.

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BOSCH, Caroline. Total Synthesis of Phlegmarine Alkaloids. [consulta: 28 de gener de 2026]. [Disponible a: https://hdl.handle.net/2445/106167]

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