New 4,12-dideoxyphorbol esters from Euphorbia pannonica Host

Ingenane, tigliane and daphnane diterpenes, called in common as phorboids, are typical constituents of the families Euphorbiaceae and Thymelaeaceae. Earlier studies on these compounds focused mainly on their powerful skin irritant and tumour promoting activities, which are the result of their protein kinase C activating potential. Further investigations have disclosed much wider pharmacological activities e.g. cytotoxic, antileukemic, antiviral, sedative and analgesic effects [1,2,3]. As part of our ongoing search for biologically active compounds from Hungarian Euphorbiaceae, we report herein the isolation and structure determination of two new diterpenes from Euphorbia pannonica Host. This plant is a perennial herb native to south, eastern and central regions of Europe. Phytochemical or biological investigations on E. pannonica have not been reported previously.

The methanolic extract of the dried whole plants of E. pannonica was subjected to solvent partitioning to furnish dichloromethane and water-soluble fractions. The organic phase was fractionated by column chromatography on polyamide, then by vacuum liquid chromatography on silica gel. Selected fractions from these separations were further purified by CPC, preparative TLC and HPLC to yield two pure compounds. The structure elucidation was carried out by extensive NMR studies using advanced experiments (¹H NMR, JMOD, ¹H-¹H COSY, HSQC and HMBC). The isolated compounds were identified as 4,12-dideoxyphorbol-20-benzoate-13-isobutyrate and 4,12-dideoxyphorbol-20-benzoate-13-isovalerianate. 4,12-dideoxyphorbols occur rarely, only the parent alcohol and its two esters were isolated earlier from Excoecaria bicolor [4].

References: [1] Fatope, M.O. et al. (1996) J Med Chem 39: 1005–1008. [2] El-Mekkawy, S. et al. (2000) Phytochemistry 53: 457–464. [3] Ma, Q.-G. et al. (1997) Phytochemistry 44: 663–666. [4] Karalai, C. et al. (1995) Phytother Res 9: 482–488.