Probing host-selective phytotoxicity: synthesis of destruxin B and several natural analogues. |
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Authors: | D E Ward Y Gai R Lazny M S Pedras |
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Affiliation: | Department of Chemistry, University of Saskatchewan, 110 Science Place, Saskatoon SK S7N 5C9, Canada. dale.ward@usask.ca |
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Abstract: | The syntheses of the host-selective phytotoxin destruxin B [cyclo(betaAla-Hmp-Pro-Ile-MeVal-MeAla), Hmp = (2R)-2-hydroxy-4-methylpentanoic acid], and the closely related natural analogues homodestruxin B (MeVal-->MeIle), desmethyldestruxin 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-betaAla linkage was formed by cyclization and the precursor linear hexadepsipeptides were formed by condensing two three-residue fragments. Radiolabeled samples of destruxin B, homodestruxin B, and hydroxydestruxin B were prepared by coupling [3-(14)C]-beta-alanine to the appropriate pentadepsipeptide followed by cyclization. A noteworthy feature of the synthesis involves the novel use of a Boc-hydrazide protecting group on dipeptides with a C-terminal N-methylalanine residue to inhibit the otherwise facile dioxopiperazine formation during peptide coupling. |
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