Thapsia garganica

Thapsigargin Thapsia garganica (Apiaceae) Ca"+-AI Pase [activates... 

Thapsigargin (sesquiterpene lactone) Thapsia garganica (Apiaceae) Activates PKC (PKC-a) (Ca2+-ATPase)... 

Fig. (22). Structure of thapsigargin (TG), a guaianolide from Thapsia garganica.

Santonin (1) has been used as the starting material in the synthesis of simplified analogs of thapsigargin (185) (Figure 5), which is a selective and very potent inhibitor of the microsomal Ca + pumps that can only be isolated in poor yield from Thapsia garganica [36], Studies of structure-activity relationships have revealed that the presence of the 7,11-dihydroxy moiety is important for the Ca2+ pump inhibitory action of 185. 

Thapsic acid (hexadecanedioic acid) may be isolated from the dried roots of Thapsia garganica, a Mediterranean, umbelliferous plant, which was known already In ancient times to be poisonous (due to thapsigargin and other components). In Arabian caravans it was called "deadly carrot," because camels would eat it and die quickly... 

Occurs as esters in Thapsia garganica and in Jurtiperus sabitta. Cryst. (EtOH or EtOAc). Mp 126 . 

Biological properties and chemotaxonomic value of guaianolides have encouraged intensive studies. The best studied example is thapsigargin from Thapsia garganica L. 

Fig. 98.2 Guaianolides isolated from plants belonging to Asteraceae (3-8, 12) and Apiaceae (9-12). Compound 3 matricin fmm Matricaria chamomilla [2], 4 mpicolin A 8-0-acetate from Artemisia tripartita [2], 5 from Lasiolaena morii [9], 6 from Artemisia xanthochroa [10], 7 bacchariolide from Baccharis salicina [11], 8 cichopumolide from Cichorium pumilum [12], 9 from Hymenoxys scaposa var. villosa [13], 10 from Laser trilobum [14], 11 thapsigargin from Thapsia garganica [15], and 12 carmenin fromFerula sp. (Apiaceae) [16, 17] and from Artemisia lanata (Asteraceae) [18]...

Rasmussen U, Christensen SB, Sandberg F (1978) Thapsigargine and thapsigargicine, two new histamine liberators from Thapsia garganica L. Acta Pharm Suec 15(2) 133-140... 

Smitt UW, Moldt P, Christensen SB (1986) Structure of a pro-l,4-dimethylazulene guaianolide fi om Thapsia garganica L. Acta Chem Scand B 40 711-714... 

Liu HZ, Jensen KG, Tran LM, Chen M, Zhai L, Olsen CE, Sphoel H, Denmeade SR, Isaacs JT, Christensen SB (2006) Cytotoxic phenylpropanoids and an additional thapsigargin analogue isolated from Thapsia garganica. Phytochemistry 67(24) 2651-2658 Denmeade SR, Isaacs JT (2005) The SERCA pump as a therapeutic target making a smart bomb for prostate cancer. Cancer Biol Ther 4(l) 14-22... 

Larsen, P. K., and F. Sandberg Constituents of Umbelliferous Plants. XV. Coumarins from Thapsia garganica L. The Structure of a New Coumarin. Acta Chem. Scand. 24, 1113 (1970). 

Thapsigargin, a highly oxidized sesquiterpenoid, is a potent SERCA pump inhibitor [20] isolated from Mediterranean plant Thapsia garganica [21], This compound is of considerable pharmacological interest as a tumor promoter and as a potent activator of cells involved in the inflammatory response. Its biosynthesis has not yet fully elucidated but it is proposed to invoke FDP cyclization to... 

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