Modular total syntheses of mycolactone A/B and its [ 2 H]- isotopologue

Sarah Saint-Auret (1) , Hajer Abdelkafi (1) , Didier Le Nouen (2) , Laure Guenin-Macé (3) , Caroline Demangel (3) , Philippe Bisseret (1) , Nicolas Blanchard (1)

1 LCM - Laboratoire de chimie moléculaire
2 COB - Laboratoire de Chimie organique et bioorganique
3 Immunobiologie de l'Infection - Immunobiology of Infection

A modular total synthesis of mycolactone A/B, the exotoxin produced by Mycobacterium ulcerans has been achieved through the orchestration of several Pd-catalyzed key steps. While this route leads to a mixture of the natural product and its C12 epimer (4:1 ratio), this was inconsequential from the biological activity standpoint. Compared to previously reported routes, this synthetic blueprint allows the late-stage modification of the toxin, as exemplified with the preparation of [22,22,22-2

Domains: Life Sciences [q-bio]; Biochemistry, Molecular Biology; Life Sciences [q-bio]; Toxicology

Sarah Saint-Auret, Hajer Abdelkafi, Didier Le Nouen, Laure Guenin-Macé, Caroline Demangel, et al.. Modular total syntheses of mycolactone A/B and its [ 2 H]- isotopologue. Organic & Biomolecular Chemistry, 2017, 15, pp.7518-7522. ⟨10.1039/C7OB01943B⟩. ⟨pasteur-01666631⟩