Total synthesis and biological evaluation of tamandarin B analogues.
Tamandarins A and B are a class of marine natural cyclodepsipeptides with structures and biological activities closely related to those of the didemnins. The easier synthetic access to tamandarins accelerates the preparation of new macrocyclic derivatives of this family of antitumor, antiviral, and immunosuppressive compounds. The optimization of the previously reported synthetic route to tamandarins by changing the macrolactamization site from Nst1 and Thr6 to Pro4 and N,O-Me2Tyr5 residues led to a significant improvement in the reaction yield. Using this new synthetic approach, four new macrocyclic analogues of tamandarin B were prepared and evaluated for anticancer activity. These results provide further insight into the structure-activity relationship of the tamandarins and didemnins.
Adrio
Javier
J
Departamento de Química Orgánica, Facultad de Ciencias, Universidad Autónoma de Madrid, 28049 Madrid, Spain.
Cuevas
Carmen
C
Manzanares
Ignacio
I
Joullié
Madeleine M
MM
D000596:Amino Acids / Q000737:chemistry; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D047630:Depsipeptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity*; D006801:Humans; D008745:Methylation; D015394:Molecular Structure; D009281:Naphthalenes / Q000737:chemistry
D000596:Amino Acids; D047630:Depsipeptides; D009281:Naphthalenes; C433835:tamandarin B; C031721:naphthalene; C030051:didemnins