Modular Enantioselective Synthesis of an Advanced Pentahydroxy Intermediate of Antimalarial Bastimolide A and of Fluorinated and Chlorinated Analogues

Adrien Quintard (1) , Céline Sperandio (1) , Jean Rodriguez (1)

1 ISM2 - Institut des Sciences Moléculaires de Marseille

A short enantioselective catalytic synthesis of the key C15−C27 fragment of bastimolide A, a natural product showing promising antimalarial bioactivity, is disclosed. The strategic insertion of halogen atoms such as fluorine and chlorine by enantioselective organocatalytic halogenations allowed an excellent stereochemical control for the formation of complex acyclic fragments bearing up to four stereogenic centers. Furthermore, besides the formation of the 1,5,7,9,13-pentahydroxy fragment of the natural product, this strategy opens the route to the modulation of the bioactivity by halogenohydrins.

Mots clés: Organocatalysis; metal catalysis; Multi-catalysis; natural products; organic synthesis

Domaines: Chimie organique; Chimie thérapeutique

Adrien Quintard, Céline Sperandio, Jean Rodriguez. Modular Enantioselective Synthesis of an Advanced Pentahydroxy Intermediate of Antimalarial Bastimolide A and of Fluorinated and Chlorinated Analogues. Organic Letters, 2018, 20 (17), pp.5274 - 5277. ⟨10.1021/acs.orglett.8b02213⟩. ⟨hal-01871735⟩