Probing host-selective phytotoxicity: Synthesis of destruxin B and severalnatural analogues

The syntheses of the host-selective phytotoxin destruxin B [cyclo(beta Ala- Hmp-Pro-Ile-MeVal-MeAla), Hmp = (2R)-2-hydroxy-4-methylpentanoic acid], and the closely related natural analogues homodestruxin B (MeVal --> MeIle), d esmethyldestruxin B (MeVal --> Val), hydroxydestruxin B (Hmp --> Dhmp, Dhmp = (2R)-2,4-dihydroxy-4-methylpentanoic acid), and hydroxyhomodestruxin B ( MeVal --> MeIle, Hmp-Dhmp) are described. In each case, the MeAla-beta Ala linkage was formed by cyclization and the precursor linear hexadepsipeptide s were formed by condensing two three-residue fragments. Radiolabeled sampl es of destruxin B, homodestruxin B, and hydroxydestruxin B were prepared by coupling [3-C-14]-beta -alanine to the appropriate pentadepsipeptide follo wed by cyclization. A noteworthy feature of the synthesis involves the nove l use of a Boc-hydrazide protecting group on dipeptides with a C-terminal N -methylalanine residue to inhibit the otherwise facile dioxopiperazine form ation during peptide coupling.