Synthesis and biological evaluation of tamandarin B analogues.

[structure: see text]. The synthesis of two tamandarin B analogues in which the N,O-Me2Tyr5 unit was replaced by N-Me-phenylalanine (N-MePhe5) and (S)-2-(methylamino)-3-(naphthalen-2-yl)propanoic acid (N-MeNaphth5) is described. The choice of the macrocyclization site was crucial to achieve satisfactory macrolactamization. Coupling between norstatine (Nst1) and threonine (Thr6) afforded only a 15% yield, while lactamization between proline (Pro4) and the aromatic moiety could be achieved in 65% yield.