Stellatolides, a new cyclodepsipeptide family from the sponge Ecionemia acervus: isolation, solid-phase total synthesis, and full structural assignment of stellatolide A.
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.
Research and Development, PharmaMar, S. A. , Avenida de los Reyes 1, 28770 Colmenar Viejo, Madrid, Spain.
María Jesús
MJ
Martín
Raquel
R
Rodríguez-Acebes
Yésica
Y
García-Ramos
Valentín
V
Martínez
Carmen
C
Murcia
Isabel
I
Digón
Isabel
I
Marco
Marta
M
Pelay-Gimeno
Rogelio
R
Fernández
Fernando
F
Reyes
Andrés M
AM
Francesch
Simon
S
Munt
Judit
J
Tulla-Puche
Fernando
F
Albericio
Carmen
C
Cuevas
D000818:Animals; D047630:Depsipeptides / Q000138:chemical synthesis / Q000737:chemistry / Q000302:isolation & purification*; D015394:Molecular Structure; D011161:Porifera / Q000737:chemistry*; D021241:Spectrometry, Mass, Electrospray Ionization
D047630:Depsipeptides; C000597782:stellatolide A