Multifaceted Study on a Cytochalasin Scaffold: Lessons on Reactivity, Multidentate Catalysis, and Anticancer Properties

Mehdi Zaghouani (1) , Oscar Gayraud (2) , Vincent Jactel (2) , Sébastien Prevost (2) , Ambre Dezaire (3, 4) , Michèle Sabbah (5) , Alexandre E. Escargueil (5) , Thanh-Lan Lai (6) , Christophe Le clainche (7) , Nathalie Rocques (8) , Stéphane Romero (8) , Alexis Gautreau (8) , Florent Blanchard (9) , Gilles Frison (10) , Bastien Nay (2, 4)

1 MCAM - Molécules de Communication et Adaptation des Micro-Organismes
2 DCSO - Laboratoire de synthèse organique
3 CRSA - Centre de Recherche Saint-Antoine
4 MCAM - Molécules de Communication et Adaptation des Micro-organismes
5 UMRS893 - Centre de Recherche Saint-Antoine
6 IBITECS - Institut de Biologie et de Technologies de Saclay
7 I2BC - Institut de Biologie Intégrative de la Cellule
8 BIOC - Laboratoire de Biochimie de l'Ecole polytechnique
9 ICSN - Institut de Chimie des Substances Naturelles
10 LCM - Laboratoire de chimie moléculaire

We report an intramolecular Diels-Alder reaction efficiently accelerated by Schreiner's thiourea, to build a functionalized cytochalasin scaffold (periconiasin series) amenable to biological purpose. DFT calculation highlighted a unique multidentate cooperative hydrogen bonding in this catalysis. The deprotection end-game afforded a collection of diverse structures and showed the peculiar reactivity of the Diels-Alder cycloadducts upon functionalization. Biological studies revealed strong cytotoxicity of a few compounds on breast cancer cell lines, while preserving actin polymerization.

Domaines: Chimie; Chimie organique

Mehdi Zaghouani, Oscar Gayraud, Vincent Jactel, Sébastien Prevost, Ambre Dezaire, et al.. Multifaceted Study on a Cytochalasin Scaffold: Lessons on Reactivity, Multidentate Catalysis, and Anticancer Properties. Chemistry - A European Journal, 2018, 24 (62), pp.16686-16691. ⟨10.1002/chem.201804023⟩. ⟨hal-02135339⟩