Biomimetic total synthesis of meiogynin A, an inhibitor of Bcl-xL and Bak interaction

Dalia Fomekong Fotsop; Fanny Roussi; Aurélie Leverrier; Anne Bretéché; Françoise Guéritte

doi:10.1021/jo101088h

Biomimetic total synthesis of meiogynin A, an inhibitor of Bcl-xL and Bak interaction

J Org Chem. 2010 Nov 5;75(21):7412-5. doi: 10.1021/jo101088h.

Authors

Dalia Fomekong Fotsop¹, Fanny Roussi, Aurélie Leverrier, Anne Bretéché, Françoise Guéritte

Affiliation

¹ Centre de recherche de Gif, Institut de Chimie des Substances Naturelles, CNRS, UPR 2301, 1, avenue de la terrasse, 91198 Gif sur Yvette, France.

PMID: 20929197
DOI: 10.1021/jo101088h

Abstract

A short, convergent, and selective synthesis of meiogynin A, an inhibitor of the antiapoptotic protein Bcl-xL, has been performed. This synthesis, based on a biomimetic approach, allowed the determination of its absolute configuration. Three isomers of meiogynin A have also been elaborated. One of these was found to be three times more potent than the natural compound.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Biomimetics*
Isomerism
Protein Binding / drug effects
Sesquiterpenes / chemical synthesis*
Sesquiterpenes / chemistry
Sesquiterpenes / pharmacology*
bcl-2 Homologous Antagonist-Killer Protein / metabolism*
bcl-X Protein / metabolism*

Substances

Sesquiterpenes
bcl-2 Homologous Antagonist-Killer Protein
bcl-X Protein
meiogynin A