Total solid-phase synthesis of marine cyclodepsipeptide IB-01212.
A suitable combination of synthetic design, orthogonal protecting groups and coupling reagents was used to complete the first known synthesis of the natural marine cyclodepsipeptide IB-01212. The cyclic, symmetric octapeptide contains two of each of the following residues: L-N,N-Me2Leu, L-Ser, L-N-MeLeu and L-N-MePhe. IB-01212 also features two symmetric ester bonds between the hydroxyl group of Ser and the carboxyl function of the N-MePhe. Total solid-phase syntheses of the product was performed in parallel via three distinct routes: dimerization of heterodetic fragments, linear synthesis, and convergent synthesis. The convergent strategy gave the best results in terms of product yield and purity and is particularly suitable for the large-scale synthesis of IB-01212 and similar peptides.
Cruz
Luis J
LJ
Barcelona Biomedical Research Institute, Barcelona Science Park, University of Barcelona, 08028-Barcelona, Spain.
Cuevas
Carmen
C
Cañedo
Librada M
LM
Giralt
Ernest
E
Albericio
Fernando
F
D000903:Antibiotics, Antineoplastic / Q000138:chemical synthesis*; D047630:Depsipeptides / Q000138:chemical synthesis* / Q000737:chemistry; D019281:Dimerization
D000903:Antibiotics, Antineoplastic; D047630:Depsipeptides; C519452:IB-01212