Santonin from Artemisia maritima

Santonin (7.30) occurs in the oil known as Levant Wormseed Oil. This oil is not extracted from the seeds, but from the unopened flower heads of several herbs of the family Artemisia, principally from Artemisia maritima. Its use in folk medicine for the treatment of intestinal worms stems from the anthelmintic properties of santonin. Santonin undergoes a number of very interesting reactions, three of which are summarised in Figure 7.9. 

Artemisin (2) is an 8-hydroxy-functionalized eudesmanolide that is isolated from Artemisia maritima and is closely related to santonin, and is a compound that has been successfully used by our group in several syntheses of sesquiterpenolides functionalized at C(8) or C(9). For example, artemisin (2) has been transformed into the cytotoxic compounds artapshin (147) and dihydro-8a-hydroxybalchanin (148) [28] in a synthetic sequence (Scheme 19) in which the transformation of the A ring was achieved in a similar way to that described previously in the synthesis of dihydrosantamarin (see Scheme 8). 

Santonin (130), a sesquiterpene lactone from Artemisia maritima (Asteraceae) has been used as an ascaricide, and is especially active against roundworms (Ascaris spp.). 

Artemisin. 3a,5,5a,9b-Tetrahydro-4-hydroxy-3,5a, 9.trimethylnaphlho[l, 2-bffu ran-2,8(3H,4H l-dione 6a,8ct-dihydroxy-3-oxoeudesma-l,4-dien-12-oie acid 12,6-lactone 8-hydroxysantonin. C jH S04 mol wt 262.29, C 68.68%, H 6.92%, O 24.40%. From the closed, unexpanded flower heads of several Artemisia spp, especially Artemisia maritima L., and A. clna Berg., Compositae ( wormseed ). Found in the mother liquors from the extraction of santonin. Isoln E. Merck, Merck s Jahresber. 1894, 3 Chem. Zentr. 1895, I, 436. Structure Sumi. J. Am. Chem. Soc. 80, 4869 (1958) Cocker, McMurry, Tetrahedron 8, l8l (1960). Stereochemistry Bolt et of., J. Chem. Soc 1963, 5235. Synthesis of (+) -artemisin Nakazaki, Naemura, Tetrahedron Letters 1966, 2615. 

Several struetural variants of laetones derived from eudesmane oceur in Artemisia-species (Asteraeeae). These include various 3-oxo-12,6-eudesmanolides such as (+)-santonane from the flowers of A. pauciflora, (-)-taurin from A. taurica (not to be confused with taurine = 2-aminoethanesulfonic acid) and the antihelmintic but toxic santonines isolated from the dried unexpanded flowerheads of A. maritima (contents up to 1.5% of a-santonin) and allied species. 

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