Entropically Favorable Macrolactamization. Synthesis of Isodityrosine Peptide Analogues by Tandem Erlenmeyer Condensation−Macrolactamization

Macrolactams containing a modified isodityrosine moiety were assembled by direct addition of a bis-4-aryliden-5(4H)-oxazolone, derived by double Erlenmeyer condensation of diaryl ether dicarboxaldehydes and an α,ω-diamine, derived from the same precursor. Tandem acylation of diamines with the bis-Erlenmeyer oxazolone gave macrolactams in yields of up to 30%. TECM demonstrates an entropically controlled 28-membered ring closure and allows rapid access to a variety of cyclic isodityrosine peptide analogues of the biologically active natural product bastadin-5.