Probing host-selective phytotoxicity: synthesis of destruxin B and several natural analogues.
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.
Ward
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DE
Department of Chemistry, University of Saskatchewan, 110 Science Place, Saskatoon SK S7N 5C9, Canada. dale.ward@usask.ca
Gai
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Y
Lazny
R
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Pedras
M S
MS
D001937:Brassica / Q000187:drug effects / Q000382:microbiology; D047630:Depsipeptides; D004351:Drug Resistance; D015335:Molecular Probes; D009183:Mycotoxins / Q000138:chemical synthesis* / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000494:pharmacology; D018515:Plant Leaves / Q000187:drug effects / Q000382:microbiology
D047630:Depsipeptides; D015335:Molecular Probes; D009183:Mycotoxins; D010456:Peptides, Cyclic; C086296:homodestruxin B; C040424:destruxin B