Structure elucidation of bioactive constituents of Baccharis gaudichaudiana

A highly sweet novel labdane-type diterpene arabinoside, gaudichaudioside A, was isolated from the 1-butanol extract of the aerial parts of the sweet-tasting plant, Baccharis gaudichaudiana, which were collected in Paraguay, following ethnobotanical leads. With the use of 1D- and 2D-NMR experiments, the structure of this compound was elucidated as 15,19-dihydroxylabda-8(9)-13(14)E-dien-17-al-6{dollar}alpha{dollar}-O-{dollar}alpha{dollar}- scL-arabinopyranoside. Gaudichaudioside A was established as being non-toxic for mice and non-mutagenic toward Salmonella typhimiurium. Also isolated from this same extract were two novel diterpene arabinosides, gaudichaudiosides B and C, whose structures were determined as 15,17,19-trihydroxylabda-8(9),13(14)E-dien-6{dollar}alpha{dollar}- scL-arabinopyranoside and 2{dollar}alpha{dollar},15,17,19-tetrahydroxylabda-8(9),13(14)E-dien-6{dollar}alpha{dollar}-O-{dollar}alpha{dollar}- scL-arabinopyranoside, respectively. Gaudichaudiosides B and C were, in turn, found to be sweet-bitter and neutral-tasting, respectively.; On chromatographic separation of the ethyl acetate extract, twelve compounds were isolated, comprising three novel labdane-type arabinosides, gaudichaudiosides D-F, three novel labdane-type diterpene alcohols, gaudichaudols A-C, one novel clerodane-type diterpene, gaudichaudone, the known clerodane-type diterpene, articulin acetate, the known flavonoids, apigenin and hispidulin, the known sesquiterpene alcohol, spathulenol, and the known triterpene, ursolic acid.; Through the application of 1D- and 2D-NMR experiments, the structures of gaudichaudiosides D-F determined as 8{dollar}alpha{dollar},15,19-trihydroxylabda-13(14)E-en-6{dollar}alpha{dollar}-O-{dollar}alpha{dollar}- scL-arabinopyranoside, 2{dollar}alpha{dollar},8{dollar}alpha{dollar},15-trihydroxylabda-13(14)E-en-6{dollar}alpha{dollar}-O-{dollar}alpha{dollar}- scL-arabinopyranoside and 15,22-dihydroxy-19-oxo-17-trihomolabad-8(9),13(14)E-17(18)E-trien-6{dollar}alpha{dollar}-O-{dollar}alpha{dollar}- scL-arabinopyranoside, respectively. Gaudichaudioside F possessed an unprecedented 23-carbon aglycone. Gaudichaudiosides D-F were, in turn, found to be bitter, sweet-bitter and bitter-tasting. The structures of gaudichaudols A-C were established as 15,16,18,19-tetrahydroxylabda-5-ene, 15-O-acetyl-16,18,19-trihydroxylabda-5-ene and 16-p-t-O-coumaroyl-15,18,19-trihydroxylabda-5-ene, respectively, while the structure of gaudichaudone was assigned as 2{dollar}beta{dollar}-hydroxy-15,16-epoxy-cleroda-1(10)-15,16-trien-18,19-olide. The remaining known compounds, articulin acetate, hispidulin, apigenin, spathulenol and ursolic acid were identified by comparing the spectral parameters obtained in this investigation with those reported in the literature for these substances.; Among the isolates obtained in this study, gaudichaudol C, articulin acetate and hispidulin were found to be cytotoxic constituents. Gaudichaudol C was active against the P-388 murine lymphocytic leukemia (ED{dollar}sb{lcub}50{rcub}{dollar} 2.4 {dollar}mu{dollar}g/ml) and marginally active against vinblastine-resistant KB-V1 (ED{dollar}sb{lcub}50{rcub}{dollar} 4.7 {dollar}mu{dollar}g/ml) cells. Hispidulin was active against the P-388 (ED{dollar}sb{lcub}50{rcub}{dollar} 0.8 {dollar}mu{dollar}g/ml) and KB-V1 (ED{dollar}sb{lcub}50{rcub}{dollar} 2.8 {dollar}mu{dollar}g/ml) cell lines, while articulin acetate was cytotoxic only toward the P-388 cell line.