Article Dans Une Revue Tetrahedron Année : 2012

Single- and double-chained truncated jaspine B analogues: asymmetric synthesis, biological evaluation and theoretical study of an unexpected 5-endo-dig process

Résumé

An optimized synthesis of jaspine B analogues bearing an n-octyl or a p-fluorophenethyl lipophilic appendage was developed. Key to the approach was the use of acetylenic nucleophiles for the stereocontrolled introduction of the side chain and the implementation of a novel cyclization procedure to build the tetrahydrofuran ring. Three N-substituted amine or amide derivatives were also accessed. The biological activity of these four jaspine B analogues was shown to strongly depend on the nature of both the N-substituent and the aliphatic moiety connected to the tetrahydrofuran ring. Gratifyingly, the truncated jaspine B derivative proved to be a pro-apoptotic inhibitor of the conversion of ceramide into sphingomyelin. Finally, the efficient formation of a fused bis-furan derivative according to a 5-endo-dig process was observed under saponification conditions. On the basis of a theoretical study, a mechanistic pathway was delineated highlighting the Lewis acidity of the K þ ion as the driving force for this transformation in a strongly alkaline medium.

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inserm-04963295 , version 1 (24-02-2025)

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Yahya Salma, Stéphanie Ballereau, Sonia Mallet-Ladeira, Christine Lepetit, Rémi Chauvin, et al.. Single- and double-chained truncated jaspine B analogues: asymmetric synthesis, biological evaluation and theoretical study of an unexpected 5-endo-dig process. Tetrahedron, 2012, 67, pp.4253 - 4262. ⟨10.1016/j.tet.2011.04.027⟩. ⟨inserm-04963295⟩
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