Submitted to: Journal of Agricultural and Food Chemistry
Publication Type: Peer reviewed journal
Publication Acceptance Date: 9/21/2005
Publication Date: 12/14/2005
Citation: Krasnoff, S.B., Lobkovsky, E., Wach, M.J., Loria, R., Gibson, D.M. 2005. Chemistry and phytotoxicity of thaxtomin a alkyl ethers. Journal of Agricultural and Food Chemistry. 53(24):9445-9451. Interpretive Summary: Several Streptomyces species cause “scab” diseases on potato tubers, sweet potato storage roots and expanded tap roots of radish, beet and similar crops. All of these species produce a family of toxins known as thaxtomins that are critical for pathogenicity, and these compounds also possess potent herbicidal activity. This work describes the production of a series of thaxtomin derivatives that afforded the opportunity to investigate the key structural components required for activity. We found that only a specific configuration of the compound was active and that additional groups added at carbon position 14 had reduced activity. These studies will be useful for defining the chemical requirements responsible for herbicidal activity.
Technical Abstract: The thaxtomin phytotoxins (1, 2) from scab-producing Streptomyces pathogens of potato are 2,5-dioxopiperazines consisting of modified L-tryptophanyl- and L-phenylalanyl-units. Thaxtomin A (1) is hydroxylated at C-14, the a-carbon of the modified L-phenylalanyl moiety. Refluxing thaxtomin A in acidified MeOH, EtOH, and iPrOH afforded C-14 thaxtomin A methyl- (3a, b), ethyl- (4a, b), and isopropyl- (5a, b) ethers respectively in both the L,L (3a, 4a, 5a) and L,D configuration (3b, 4b, 5b). Crystal structures were determined for 3a and 4a. Extensive NMR as well as other spectral data supported structural assignments for all of the derivatives. The L,L-configured derivatives were slightly less potent than the natural products (1, 2) as inhibitors of lettuce seedling root growth, whereas the activity of the L,D epimers was much reduced, indicating that the L-configuration at C-14 in the naturally-occurring thaxtomins is essential for biological activity. Among the L,L-configured compounds, potency decreased with increasing size of the substituted alkyl group. This is consistent with previous findings of others that glucosylation at C-14 reduces the phytotoxicity of thaxtomin A.