2006 Feb 2
Synthesis and Biological Evaluation of Tamandarin B Analogues.
Adrio J, Cuevas C, Manzanares I, Joullie MM.
Department of Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6323, Departamento de Quimica Organica, Faculdad de Ciencias, Universidad Autonoma de Madrid, 28049 Madrid, Spain, and Pharma Mar S.A., Sociedad Unipersonal, Avd. de los Reyes, 1.P.I. La Mina Norte 28770 Colmenar Viejo, Spain.
The synthesis of two tamandarin B analogues in which the N,O-Me(2)Tyr(5) unit was replaced by N-Me-phenylalanine (N-MePhe(5)) and (S)-2-(methylamino)-3-(naphthalen-2-yl)propanoic acid (N-MeNaphth(5)) is described. The choice of the macrocyclization site was crucial to achieve satisfactory macrolactamization. Coupling between norstatine (Nst(1)) and threonine (Thr(6)) afforded only a 15% yield, while lactamization between proline (Pro(4)) and the aromatic moiety could be achieved in 65% yield .