Synthesis of Optically Active Monoacid Side-Chains of Cephalotaxus Alkaloids

Farouk Berhal , Sébastien Tardy (1) , Joelle Pérard-Viret (2) , Jacques Royer (2)

1 ICOA - Institut de Chimie Organique et Analytique
2 UMR 8638 - Equipe Pharmacognosie

The general preparation of enantiopure monoacid sidechains of several esters of cephalotaxine is described. The strategy, similar to Weinreb’s approach to the synthesis of deoxyharringtonine, used as key intermediate the chiral nonracemic epoxide 11a prepared from the commercially available monomethyl itaconate (8). The key step of the strategy was the ring-opening of the epoxide 11a by using different organo-cuprate nucleophiles. Hydrogenolysis as the final step gave the monacid side-chains of the corresponding esters of cephalotaxine in moderate to good overall yields from epoxide 11a.

Mots clés: Chirality; Ring-opening; Epoxides; Esters; Alkaloids

Domaines: Chimie organique; Chimie thérapeutique

Farouk Berhal, Sébastien Tardy, Joelle Pérard-Viret, Jacques Royer. Synthesis of Optically Active Monoacid Side-Chains of Cephalotaxus Alkaloids. European Journal of Organic Chemistry, 2009, 2009 (3), pp.437-443. ⟨10.1002/ejoc.200800935⟩. ⟨hal-02372735⟩