Assembly of the Entire Carbon Backbone of a Stereoisomer of the Antitumor Marine Natural Product Hemicalide

Camille Lecourt; Sabrina Dhambri; Khalil Yamani; Guillaume Boissonnat; Simon Specklin; Etienne Fleury; Karim Hammad; Eric Auclair; Serge Sablé; Antonio Grondin; Paola B Arimondo; François Sautel; Georges Massiot; Christophe Meyer; Janine Cossy; Geoffroy Sorin; Marie-Isabelle Lannou; Janick Ardisson

doi:10.1002/chem.201806327

Assembly of the Entire Carbon Backbone of a Stereoisomer of the Antitumor Marine Natural Product Hemicalide

Chemistry. 2019 Feb 21;25(11):2745-2749. doi: 10.1002/chem.201806327. Epub 2019 Jan 25.

Authors

Camille Lecourt^{1

2}, Sabrina Dhambri¹, Khalil Yamani², Guillaume Boissonnat², Simon Specklin², Etienne Fleury¹, Karim Hammad¹, Eric Auclair³, Serge Sablé³, Antonio Grondin⁴, Paola B Arimondo⁴, François Sautel⁴, Georges Massiot⁴, Christophe Meyer², Janine Cossy², Geoffroy Sorin¹, Marie-Isabelle Lannou¹, Janick Ardisson¹

Affiliations

¹ CNRS (UMR8638), Faculté de Pharmacie, Université Paris Descartes, 4 avenue de l'observatoire, 75270, Paris Cedex 06, France.
² Laboratory of Organic Chemistry, Chemistry, Biology, Innovation, ESPCI Paris, CNRS (UMR8231), PSL Research University, 10 rue Vauquelin, 75231, Paris Cedex 05, France.
³ Sanofi R&D, Centre de Recherche de Vitry-Alfortville, 13 quai Jules Guesde, 94403, Vitry-sur-Seine Cedex, France.
⁴ Pharmacochimie de la Régulation Epigénétique du Cancer (ETac), CNRS-Pierre Fabre (USR3388), 3 avenue Hubert Curien, 31035, Toulouse Cedex 01, France.

PMID: 30600846
DOI: 10.1002/chem.201806327

Abstract

A strategy for the assembly of the entire carbon backbone of a stereoisomer of the antitumor marine natural product hemicalide has been investigated. The devised convergent approach relies on Horner-Wadsworth-Emmons and Julia-Kocienski olefination reactions for the construction of the C6=C7 and C34=C35 double bonds, respectively, an aldol reaction to create the C27-C28 bond, and a Suzuki-Miyaura cross-coupling as the endgame to form the C15-C16 bond.

Keywords: hemicalide; multistep synthesis; natural products; polyketides; stereochemistry.