Submitted to: Journal of Natural Products
Publication Type: Peer reviewed journal
Publication Acceptance Date: 12/21/2002
Publication Date: 2/5/2003
Citation: SMITH, L.R., MAHONEY, N.E., MOLYNEUX, R.J. SYNTHESIS AND STRUCTURE-PHYTOTOXICITY RELATIONSHIPS OF ACETYLENIC PHENOLS AND CHROMENE ANALOGS FROM THE GRAPEVINE PATHOGEN EUTYPA LATA.. JOURNAL OF NATURAL PRODUCTS. v. 66. p.169-176. 2003. Interpretive Summary: Dying-arm disease of grapevines is produced by a fungus that infects the vine. The problem is worldwide and has been estimated to cause losses exceeding $260 million in California alone. Methods are urgently needed to predict infected vines and remove them as a source of infection. The fungus produces a number of compounds that are potentially toxic to the vine. In order to establish which of these compounds are actually toxic, a series of them have been prepared by chemical synthesis, in order to obtain sufficient amounts to test their biological activity. A simple and rapid method has been developed for determining toxic activity, involving application of test compounds to grape leaf disks. The loss of the green plant pigment, chlorophyll, provides a measure of the activity of each compound. Whereas some of the compounds were inactive, others were very active. The active compounds may be useful as specific markers for presence of the fungus in infected grapevines.
Technical Abstract: Eutypa lata, the fungus responsible for dying-arm disease in grapevines, produces a number of structurally related secondary metabolites of which eutypine (1) has been implicated as the principal phytotoxin. However, analysis of an E. lata strain from California known to be pathogenic to grapevines showed that eutypine was not present, suggesting that other metabolites could be phytotoxic. A lack of sufficient quantities of individual metabolites and a reliable bioassay has limited comparison of the relative phytotoxicities of these compounds. Metabolites of particular interest and their precursors were therefore synthesized by new or improved methods and a rapid, quantitative bioassay via topical application of individual compounds to discs of grape leaves and measurement of chlorophyll loss was developed to provide a quantitative measure of tissue damage. The recently reported metabolite, eulatachromene (2), was found to have phytotoxicity greater than that of eutypine (1). Furthermore, the eutypine cyclization product, 5-formyl-2-methylvinylbenzofuran (3), also showed significant activity whereas the reduction product, eutypinol (4) was inactive, as previously reported. These results indicate that before strains of Eutypa are incriminated as pathogenic they must be analyzed for the presence or absence of specific constituents for which the phytotoxicity has been unequivocally established.