ACYL SECOIRIDOIDS AND ANTIFUNGAL CONSTITUENTS FROM GENTIANA MACROPHYLLA

LC-UV-mass spectrometry and bioassay co-directed fractionation of an a queous acetone extract of the roots of Gentiana macrophylla gave three new chromene derivatives and two novel and six known secoiridoids, al ong with kurarinone, kushenol I, beta-sitosterol, stigmasterol, daucos terol, beta-sitosterol-3-O-gentiobioside, alpha-amyrin, oleanolic acid , isovitexin, gentiobiose and methyl 2-hydroxy-3-(1-beta-D-glucopyrano syl)oxybenzoate. The structures of the new products were established f rom spectral and chemical evidence as 2-methoxyanofinic acid and macro phyllosides A-D. The six known secoiridoids were gentiopicroside, swer oside, 6'-O-beta-D-glucosylgentiopicroside, 6'-O-beta-D-glucosylsweros ide, trifloroside and rindoside. The new acid (2-methoxyanofinic acid) , its methyl ester, kurarinone and kushenol I were shown to be active against the plant pathogenic fungus Cladosporium cucumerinum. The meth yl ester and kurarinone inhibited also the growth of the human pathoge nic yeast Candida albicans. Structure-activity relationships were stud ied. Thus, addition of a methoxyl group to the benzene nucleus of anof inic acid (2,2-dimethyl-2H-1-benzopyran-6-carboxylic acid) increased t he antifungal activity remarkably whereas glycosylation at the carboxy lic moiety was found to remove the activity. Esterification of the new acid induced its activity against C. albicans, but decreased its grow th inhibition properties against C. cucumerinum. Hydroxylation of kura rinone at the 3 beta-position removed its activity against C. albicans and decreased the inhibition of C. cucumerinum. In addition, the chem otaxonomic significance of the identified constituents is discussed.