Judit Tulla-Puche
University of Barcelona, Spain
Title: The synthesis of complex marine depsipeptides
Biography
Biography: Judit Tulla-Puche
Abstract
Marine organisms are a rich source of bioactive molecules. Among them, cyclodepsipeptides show relevant biological profiles, mostly including cytotoxic and anti HIV activities, and they are, therefore, promising candidates for medicinal chemistry programs. Herein, we report the synthesis of the potent antineoplastic agents pipecolidepsin A and Stellatolide A, “head-to-sidechain” cyclodepsipeptides, where the C-terminus is linked to a hydroxy group via an ester bond, and of thiocoraline, a byciclic thiodepsipeptide that acts as bisintercalator. The three molecules present extremely challenging structures. Pipecolidepsin A bears the unprecedented and extraordinary bulky AHDMHA residue at the branching point, which makes the construction of the extremely hindered ester bond the major synthetic challenge to overcome. On the other hand, the high propensity of the unnatural MeOD- Tyr residue in Stellatolide A to suffer decomposition is the main limitation of its assembly. Finally, Thiocoraline’s large amount of cysteines in a rather small structure represents the principal restraint. The successful solid-phase synthetic strategies that resulted in the three synthetic and active cyclodepsipeptides will be discussed.