Submitted to: Phytochemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/5/2006
Publication Date: 11/4/2005
Citation: Meepagala, K.M., Schrader, K., Wedge, D.E., Duke, S.O. 2005. Algicidal and antifungal compounds from the roots of ruta graveolens and synthesis of their analogs. Phytochemistry. 66(22): 2689-2695.
Interpretive Summary: The blue-green alga, Oscillatoria perornata is a pest in commercial catfish (Ictalurus punctatus) production ponds in the southeastern United States. This blue-green alga produces 2-methylisoborneol (MIB), which accumulates in the flesh of catfish, giving them a 'musty' off-flavor and thereby rendering them unpalatable and unmarketable. The agents currently approved by the United States Environmental Protection Agency to control off-flavor compound-producing blue-green algae, copper-based products and the pesticide diuron, are limited in their usefulness due to their persistence in the environment, lack of selectivity towards noxious blue-green algae, and little margin of safety between concentrations toxic to algae and concentrations toxic to catfish. As an alternative to these synthetic algicides, we are evaluating natural compounds and extracts from plants to discover selective and environmentally-safe algicides for use in catfish aquaculture. In our investigation of the ethyl acetate extract of the roots of the plant R. graveolens, we found the presence of constituents with selective toxicity towards O. perornata, when compared to Selenastrum capricornutum, a green alga that is found in fish production ponds and considered to be one beneficial type of phytoplankton. Separation of this extract led to the isolation of active compounds. These compounds also showed potent fungicidal activity against several agriculturally important pathogenic fungi Colletotrichum fragariae, Colletotrichum gloeosporiodes, Colletotrichum acutatum, Botrytis cineara, and Fusarium oxysporum.
Technical Abstract: Bioassay-guided fractionation of the ethyl acetate extract of Ruta graveolens roots yielded rutacridone epoxide with potent selective algicidal activity towards the 2-methyl- isoborneol (MIB) -producing blue-green alga Oscillatoria perornata, with relatively little effect on the green alga Selenastrum capricornutum. The diol- analog of rutacridone epoxide, gravacridondiol, which was also present in the same extract, had significantly less activity towards O. perornata. Rutacridone epoxide also showed significantly higher activity than commercial fungicides captan and benomyl in our micro-bioassay against the agriculturally important pathogenic fungi Colletotrichum fragariae, C. gloeosporiodes, C. acutatum, and Botrytis cineara and Fusarium oxysporum. Rutacridone epoxide is reported as a direct-acting mutagen, precluding its use as an agrochemical. In order to understand the structure activity relationships and to develop new potential biocides without toxicity and mutagenicity, some analogs containing the (2-methyloxiranyl)-dihydrobenzofuran moiety with an epoxide were synthesized and tested. None of the synthetic analogs showed comparable activities to rutacridone epoxide. The absolute stereochemistry of rutacridone was determined to be 2'(R) and that of rutacridone epoxide to be 2' (R), 3' (R) by CD and NMR analysis.