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 dicar-boxaldehydes and an alpha,omega-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.