Total synthesis of phlegmarine alkaloids

• Autores: Caroline Bosch-Tijhof
• Directores de la Tesis: Josep Bonjoch Sesé (dir. tes.), Benjamin Hohn Bradshaw (dir. tes.)
• Lectura: En la Universitat de Barcelona ( España ) en 2016
• Idioma: español
• Tribunal Calificador de la Tesis: Antoine Baceiredo (presid.), Montserrat Diéguez Fernández (secret.), Carlos Jiménez González (voc.)
• Materias:
  • Química
    • Química orgánica
      • Estructura de moléculas orgánicas
• Enlaces
  • Tesis en acceso abierto en: TDX
• Resumen

  • This doctoral thesis consists in two distinct 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 in one part in the development of an easy procedure to access enantiopure substituted octahydroindoles relevant for natural products synthesis, in a second part 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 allows to perform the first total synthesis of various phlegmarine alkaloids and also sheds 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.

    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 synthesis of (+)-serratezomine E, (-)-serralongamine, (-)-huperzine K, huperzine M and (-)-huperzine N has 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.