Function-Oriented Synthesis toward Peloruside A Analogues

Anne-Caroline Chany (1) , Frédéric Legros (1) , Heloua Haroun (1) , Uday Kumar Kundu (1) , Bohdan Biletskyi (1) , Sergii Torlak (1) , Monique Mathé-Allainmat (2) , Jacques Lebreton (2) , Aurélie Macé (3) , Bertrand Carboni (3) , Brigitte Renoux (4) , Pascal Gosselin (1) , Gilles Dujardin (1) , Catherine Gaulon-Nourry (1)

1 IMMM - Institut des Molécules et Matériaux du Mans
2 CEISAM - Chimie Et Interdisciplinarité : Synthèse, Analyse, Modélisation
3 ISCR - Institut des Sciences Chimiques de Rennes
4 IC2MP - Institut de Chimie des Milieux et Matériaux de Poitiers

A convergent and rapid synthesis of original C2,C3-unsaturated, C11,C13-keto-enol macrocycles with a peloruside A skeleton has been developed. These original unsaturated macrocycles constitute valuable platforms to access peloruside A analogues with high diversity. The four-fragment strategy implemented features two aldol-type couplings with the central C12-C14 building block TES-diazoacetone and a late-stage ring-closing metathesis. Enantiopure analogue 18ab showed antiproliferative activity in the low micromolar range on NCI and MCF7 tumor cell lines.

Keywords: Alcohols; Aldehydes; Cells; Mixtures; Toxicity

Domains: Chemical Sciences; Medicinal Chemistry; Chemical Sciences; Organic chemistry

Anne-Caroline Chany, Frédéric Legros, Heloua Haroun, Uday Kumar Kundu, Bohdan Biletskyi, et al.. Function-Oriented Synthesis toward Peloruside A Analogues. Organic Letters, 2019, 21 (9), pp.2988-2992. ⟨10.1021/acs.orglett.9b00413⟩. ⟨hal-02087811⟩