Medicinal plants of euphorbiaceae occurring and utilized in thailand. V. Skin irritants of the daphnane and tigliane type in latex of Excoecaria bicolor and the uterotonic activity of the leaves of the tree

Abstract

From latex of Excoecuria bicolor (Euphorbiaceae) four TLC-homogeneous fractions highly enriched in diterpene esters were obtained . Fraction F3 by NMR was found to be a mixture of 9,13,14-orthoester-2O-esters (la) of 5/3-hydroxyresiniferonol-6a,7a-epoxide (I). Alkaline transesterification yielded from l a a mixture of 58-hydroxyresiniferonol-6a,7a-epoxide-9,13-14-orthoesters (If) carrying unsaturated orthoester groups as a TLC-homogeneous material (final isolation of Excoecuriu factors Bl/B2, B3 and B4). The transesterification mixture also contained, according to GC-MS, methyl n-carboxylates corresponding to the even numbered C22-CJo acids from 20-positions in la. Fraction F4 by NMR contained molecular species (2a) structurally closely related to la, carrying 5/l,12~-dihydroxyresiniferonol-6a,7a-epoxide (2) as the parent alcohol. From 2a, by alkaline transesterification, a two-component mixture of Excoecuriu factors B5/B6, i.e. 5/l,12&dihydroxy-resiniferonol-6a,7a-epoxide-9,13,14-ortho(2,4,6-hexadecatrienoate)/-(2,4,6,8-hexadecatetraenoate) (2b/2c) was obtained. GC-MS of the transesterification mixture revealed methyl n-carboxylates corresponding to even numbered c 1 6 -c 3 0 acids from 20-positions in 2a (omitting CI8 and Cm). Fractions F1 and F2 by alkaline transesterifications yielded 12-deoxyphorbol (3) and its 13-(3,54etradecadienoate) 3b (Excoecuriu factor B7). Moreover 4,12-dideoxy(4a)phorbol (4), its 13-(3,5-tetradecadienoate) 4b and the natural 4-epimer of 4b 4,12-dideoxyphorbol-13-(3,5-tetradecadienoate) (5a) (new Excoecuriu factor B8) were obtained. GC-MS of the transesterification mixtures revealed mainly methyl n-carboxylates corresponding to even numbered c 1 6 -c 3 0 acids. Thus the latex and the fractions F1 and F2 contain 13,20-diesters of the parent alcohols 12-dmxyphorbol (3) and 4,12-dideoxyphorbol (5). 4,12-dideoxy(4a)phorboI (4) and its derivatives may be considered artifacts from alkaline epimerization of 5. The daphnane type Excoecuriu factors Bl-B6 are structurally very closely related to diterpenes such as yuanhuacine occurring in certain Daphne and Wikstroerniu species. Daphnane type esters of this kind are currently used routinely in China for fertility regulation. Similarly, daphnane and tigliane type Excoecuriu factors present in the latex of E . bicolor may be responsible for the uterotonic activity of its leaves utilized in Thai herbal medicine.

Tigliane Diterpenoids from the Euphorbiaceae and Thymelaeaceae Families

“…IFN γ-Inducing Activity. Five tigliane diterpene esters (49,63,65,68,241) were obtained from the leaves of Aleurites fordii and evaluated for their ability to induce IFN-γ in NK92 cells. Compounds 49 and 241 exhibited the most potent responses in IFN-γ induction that were comparable to that of the positive control, phorbol 12-myristate 13-acetate (PMA).…”

“…A new parent alcohol, 12-deoxyphorbol ( 74 ), was obtained from a variety of different plants including Excoecaria bicolor, Euphorbia triangularis, and Euphorbia resinifera . 12-Deoxyphorbol can be readily esterified at the C-13 and C-20 positions, and 12-deoxyphorbol esters exist predominantly in one of two groups.…”

Diterpenes from European Euphorbia Species Serving as Prototypes for Natural‐Product‐Based Drug Discovery

“…Two tigliane‐type diterpenes, compounds 61 and 62 (Figure 9), were isolated from the aerial parts of E. pannonica 83. These compounds are derivatives of 4,12‐dideoxyphorbol, a diterpene alcohol that is very rare in the plant kingdom, previously isolated only from Excoecaria bicolor and E. guyoniana 84,85. Furthermore, 62 is substituted with an isovalerianate group, which was found for the first time in this group of tigliane diterpenes.…”

Daphnane-Type Diterpene Orthoesters and their Biological Activities

“…Interestingly, peracetylation abolished ichtyotoxicity, suggesting that either or both the hydroxyls on ring B are essential for activity [19]. Analogues with shorter orthoester group also show a diminished piscicidal activity [20][21][22][23][24], as exemplified by excoecariatoxin (3) Fig 1). Among their analogues, simplexin (4) and the Pimelea factor P4 (5), isolated from various Pimelea spp.…”

“…Further daphnetoxin-analogues were isolated from various plants belonging to the Excoecaria, Wikstroemia and Synaptolepsis species [22][23][24]26,29,[38][39][40][41][42][43]80]. The strong irritant and tumor promoting activity of synaptolepsis factor K7 (23) is worth mention [26].…”