Orientierung der Hydroxyl‐Gruppe des (−)‐Cubebins und seines Epimeren Orientation of the Hydroxyl Group of (−)‐Cubebin and its Epimer

Abstract

Am Lignan (-)-Cubebin (1) aus Piper cubebn (Piperaceae)') und Aristolochia triangularis Cfaarnisso (Aristo1ochiaceae)z) ist die sterische Anordnung der halbacetalischen Hydroxyl-Gruppe an C-9' noch nicht gesichertl. *). Sie 1af3t sich aus dem in CDCI,/D,O aufgenommenen 300 MHz-'H-NMR-Spektrum (Tab. 1) ableiten.Die unmittelbar nach Losen von 1 exakt zu bestimmende Kopplungskonstante Js,, 9, = 4.6 Hz entspricht3) einem Diederwinkel von ca. 40" bzw. 135" zwischen dem pseudoaquatorialen') H-8' und dem Carbinolproton H-9'. Offenbar ist H-9' in der aus Ether umkristallisierten Substanz 1 (Schmp. 13 1-1 33")2) pseudoaquatorial a-standig und die Hydroxyl-Gruppe pseudoaxial P-standig angeordnet (Diederwinkel H-8'/H-9' im Dreiding-Model1 ca. 25-35", in beiden extremen Konformationen des Furanol-Ringes). Wie bei ahnlichen Lignanen4s tritt nach Losen ein 2. Signal mit abweichender Kopplungskonstanten J s~, 9' auf (Tab. l), das auf eine Epimerisierung zu ,,Epicubebin" (2) zuriickzufuhren ist, welches offenbar nach ca. 4 Tagen (Raum-Temp.) in einem Gleichgewicht mit 1 vorliegt. Der fur 2 bestimmte Wert von Js,, 9' = 1.8 Hz (CDClJ DzO) entspricht einem Diederwinkel von ca. 60" bzw. 115" 3, und damit der pseudoaquatorialen a-Stellung der Hydroxyl-Gruppe (Diederwinkel H-8'/H-9' im Dreiding-Model1 ca. 90" oder 150" je nach Konformation des Furanol-Ringe~)~). Beim Ubergang von 1 nach 2 wird zusatzlich, offenbar infolge einer Konformationsanderung des Fura-

Melanogenesis Stimulation in Murine B16 Melanoma Cells by Piper nigrum Leaf Extract and Its Lignan Constituents

“…Thus, recent reports concerning the structural elucidation of dibenzylbutyrolactol lignans based on 1 H-and 13 C-NMR spectra taken in CDCl 3 solution described that these lignans exist as a mixture of a-isomer and b-isomer. 11,12,14,15) As shown in Table 1, the ratio of a-isomer and b-isomer of 1 in CDCl 3 solution based on the signal integral value of one (9b-H) of the methylene protons was 60 : 40, in accordance with the reported ratio (60 : 40) of 1 in CHCl 3 solution.…”

“…As to NMR spectral analysis, it is noted that the dibenzylbutyrolactol lignans, such as 1 and 2, afforded characteristic NMR spectra, since it has been reported 11) that these lignans exist as an equilibrium mixture of a-isomer and b-isomer in solution accompanied with a mutarotation. According to the literature, 11) the ratios of a-isomer and b-isomer of 1 were 60 : 40 and 65 : 35 in chloroform and methanol, respectively. Thus, recent reports concerning the structural elucidation of dibenzylbutyrolactol lignans based on 1 H-and 13 C-NMR spectra taken in CDCl 3 solution described that these lignans exist as a mixture of a-isomer and b-isomer.…”

“…From analysis of the 1 H-and 13 C-NMR spectral data (Tables 1, 2) for 1 and 2, it was found that these lignans were obtained as a mixture of a-isomer and b-isomer, as previously reported for the dibenzylbutyrolactol class of lignans. 11,12,14,15) On the basis of the signal integral value of 9b-H shown in Table 1, the ratios of a-isomer and b-isomer of 1 and 2 in CDCl 3 solution were 60 : 40 and 65 : 35, respectively.…”

“…On the basis of comparison of the physicochemical data of 1 and 2 with those of the reported data, [7][8][9][10][11][12][13][14] 1 and 2 were identified as (Ϫ)-cubebin and (Ϫ)-3,4-dimethoxy-3,4-desmethylenedioxycubebin, respectively. The comparisons of 1 H-and 13 C-NMR spectral data of 1 with the reported data 11,13,14) are shown in Tables 1 and 2, respectively. From analysis of the 1 H-and 13 C-NMR spectral data (Tables 1, 2) for 1 and 2, it was found that these lignans were obtained as a mixture of a-isomer and b-isomer, as previously reported for the dibenzylbutyrolactol class of lignans.…”

Cubebin: A Small Molecule with Great Potential

“…T A (-)-cubebina tem sido geralmente identificada como uma mistura de dois diastereisômeros 8,8'-trans em C-9, 33,34,[38][39][40][41][42][43] entretanto, a configuração deste centro anomérico, bem como de outras lignanas butirolactolicas permanece obscura. Devido à sua estrutura e suas propriedades biológicas, algumas vias sintéticas tem sido propostas para a produção de cubebina e de outras lignanas com estruturas direta ou indiretamente relacionadas.…”