Towards the total synthesis of momilactones: asymmetric Diels-Alder reactions of quinones and sulfinylquinones for the synthesis of terpenes

PhD thesis defended by Loïc JEANMART (Prof. Steve LANNERS) - 08/12/2021

Prof. Steve LANNERS, UNamur, NISM/NARILIS, Laboratory of Synthetic Organic Chemistry (COS)

  • Prof. Johan WOUTERS (Département de Chimie, UNamur), Président
  • Prof. Steve LANNERS (Département de Chimie, UNamur), promoteur et secrétaire
  • Prof. Stéphane VINCENT (Département de Chimie, UNamur)
  • Dr Gilles HANQUET (ECPM, Université de Starsbourg)
  • Prof. M. Carmen CARREÑO (Université de Madrid)
  • Prof. Johan WINNE (Université de Gand)

Momilactones A and B are two secondary metabolites isolated from rice husks that participate in the defence mechanism of the rice plant.  They are pimarane diterpenes with a 4,6-transannular lactone and have been first identified as antifungal, antibacterial compounds and growth inhibitors. More recently, studies reported that momilactones showed anticancer activities against several cell lines without decreasing the viability of healthy cells, making them good candidates as potential medicinal agents.

The aim of this project was to propose the first enantioselective synthesis of momilactones using an asymmetric Diels-Alder reaction for the formation of the two first rings, and a metal-catalysed annelation for the formation of the third ring.  

In this thesis, we present the preparation of the precursors for the Diels-Alder reaction:  oxygenated dienes, quinones and sulfinylquinones. During the preparation of those starting materials, we developed new efficient and elegant synthetic methods for some of them, and we serendipitously prepared new peculiar products. We then studied the sulfinylquinones from a structural point of view and assessed their reactivity in different solvents. We finally studied the asymmetric Diels-Alder reactions for the total synthesis of momilactones, which highlighted two potential pathways towards the target molecules.