P-9 メキシコ産植物、Trichilia cuneata由来の新規修飾型フラノエレモフィラン型セスキテルペンの構造、合成、生理活性(ポスター発表の部)

Herein we report the structures of eight compounds 1〜8 isolated from Trichilia cuneata, which belongs to Maliaceae Trichilia family. This plant is one of shrubs composing the endemic medicinal plant complex in Mexico, and the crude extract exhibited the highly antioxidative activity in our bioactivity-screening. The methanol extract of dried stem bark and leaves of T. cuneata was successively purified by column chromatography on silica gel and by recycling preparative GPC (gel permeation chromatography). Among the compounds, 1, 3, and 7 were novel modified furanoeremophilane-type sesquiterpenes, and others were known compounds. Next, the antioxidative activities were evaluated for those compounds with the mitochondria and the microsomes prepared from the rat livers. As the result, both the NADH-dependent mitochondrial and NADPH-dependent microsomal lipid peroxidations were strongly inhibited by these natural products. So it is thought that those compounds might be useful as the lead compounds in the field of medicinal chemistry. Therefore, we planned total syntheses of the three new compounds 1, 3, and 7. First, as for the compounds 3 and 7, we devised a highly convergent route based on the regioselective trisubstituted furan synthesis using a palladium-catalyzed three-component coupling reaction developed by Balme et al. The naphthofuran A,B,C-ring framework could be constructed by an intramolecular Friedel-Crafts acylation of carboxylic acid 12. Next, as for the compound 1 which has a substituent at C-6 position, the different strategy from that for the compounds 3 and 7 would be needed. So we envisaged the brominated tetralin as the possible intermediate, which would be derived from the tetralone 19 via the furan ring formation. The tetralone 19 will be constructed from commercially available γ-valerolactone 20 and 4-bromoveratrole 21 by Friedel-Crafts reactions. As the result we achieved the first total syntheses of compounds 1, 3, and 7, and the spectral characteristics of three synthetic compounds were consistent with those observed for the natural products, respectively.