15 September 2006 .
Convergent Approaches for the Synthesis of the Antitumoral Peptide, Kahalalide F. Study of Orthogonal Protecting Groups.
Gracia C, Isidro-Llobet A, Cruz LJ, Acosta GA, Alvarez M, Cuevas C, Giralt E,
Albericio F.
Institute for Research in Biomedicine, Barcelona Science Park, University of Barcelona, 08028-Barcelona, Spain, Laboratory of Organic Chemistry, Faculty of Pharmacy, University of Barcelona, 08028-Barcelona, Spain, PharmaMar S.A.U., 28770-Colmenar Viejo (Madrid), Spain, and Department of Organic Chemistry, University of Barcelona, Marti i Franques 1, 08028-Barcelona, Spain.
Kahalalide compounds are peptides that are isolated from a Hawaiian herbivorous marine species of mollusc, Elysia rufescens, and its diet, the green alga Bryopsis sp. Kahalalide F and its synthetic analogues are the most promising compounds of the Kahalalide family because they show antitumoral activity. Linear solid-phase syntheses of Kahalalide F have been reported. Here we describe several new improved synthetic routes based on convergent approaches with distinct orthogonal protection schemes for the preparation of Kahaladide analogues. These strategies allow a better control and characterization of the intermediates because more reactions are performed in solution.