Stellatolides, a New Cyclodepsipeptide Family from the Sponge Ecionemia acervus: Isolation, Solid-Phase Total Synthesis, and Full Structural Assignment of Stellatolide A

• Published in: Journal of the American Chemical Society 2014-05, Vol.136 (18), p.6754-6762
• Main Authors: Martín, María Jesús, Rodríguez-Acebes, Raquel, García-Ramos, Yésica, Martínez, Valentín, Murcia, Carmen, Digón, Isabel, Marco, Isabel, Pelay-Gimeno, Marta, Fernández, Rogelio, Reyes, Fernando, Francesch, Andrés M, Munt, Simon, Tulla-Puche, Judit, Albericio, Fernando, Cuevas, Carmen
• Format: Article
• Language: English
• Subjects: Animals; Depsipeptides - chemical synthesis; Depsipeptides - chemistry; Depsipeptides - isolation & purification; Molecular Structure; Porifera - chemistry; Spectrometry, Mass, Electrospray Ionization
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja502744a

The marine environment is a rich source of metabolites with potential therapeutic properties and applications for humans. Here we describe the first isolation, solid-phase total synthesis, and full structural assignment of a new class of cyclodepsipeptides from the Madagascan sponge Ecionemia acervus that shows in vitro cytotoxic activities at submicromolar concentrations. Seven structures belonging to a new family of compounds, given the general name stellatolides, were characterized. The sequence and stereochemistry of all the amino acids in these molecules were established by a combination of spectroscopic analysis, chemical degradation, and derivatization studies. Furthermore, the complete structure of stellatolide A was confirmed by an efficient solid-phase method for the first total synthesis and the full structural assignment of this molecule, including the asymmetric synthesis of the unique β-hydroxy acid moiety (Z)-3-hydroxy-6,8-dimethylnon-4-enoic acid.