P-Santonin

Santonin (la,b), an effective drug for treating intestinal roundwormS/ was first isolated from unexpanded flower heads of Artemesia plants (Levant Wormseed) grown in Russian and Chinese Turkestan and the Southern Ural region. The structure of this compound was established by Clemo et al. [2,3] and Ruzicka and Steiner [4]. Santonin exists in two forms, a-santonin and p-santonin, the stereochemistry of which has been worked out by several workers [5-7]. 

The synthesis of a- and P-santonins (la,b) has been described by Abe and coworkers [89]. The key intermediate for preparing santonins utilizes eusantonin (38) which is obtained by condensing 3-keto-4,9-dimethyl-l,2,3,7,8,9-hexahydro-naphthalene (37) with diethyl methylmalonate. The two different routes to arrive at a-and P-santonins are given in scheme 1. 

Frullanolide (338), with a d s-lactone ring, has been isolated from the epiphytic liverwort, Frullania tamarisci. The structure was deduced from its spectral properties (775,255, 287) and confirmed by conversion to l,2-dihydro-6-epi-P-santonin (366) also obtained from 6-epi-P-santonin (367) (775, 287) (Scheme 40). The enantiomer (339) of (338) was isolated from European F, dilatata (30, 175, 287). 

Scheme 40. Correlation of (— )-frullanolide with 6-epi-p-santonin and synthesis of (—)-...

A stereocontrolled total synthesis of a-santonin (la) and the less stable P-san-tonin (lb) has been developed by Marshall and Wuts [90] which is outlined in scheme 2. 

Pentaacetoxy-9-benzoyloxy-4-hydroxy-dihydro-P-agarofiiran Triptogelin A-1 Triptofordin F-2 a-Santonin Orbiciilin H Orbiculin I Orbiculin D Trichothecinol A Trichothecinol B Trichothecinol C Trichothecin Euonymine Atractylon Germacrane... 

Costunolide-1,10-epoxide (364) has been synthesized and subsequently converted into a mixture of santamarine (365a) and reynosin (365b) under a variety of reaction conditions [cf. conversion of santonin into (365a) and (365b), p. 128]. A similar study has shown that treatment of herbolide B (366) with acidic reagents produces eudesmanolides (367) and (368) (Scheme 34). The general tendency... 

Modification of the synthetic strategy previously used " in the synthesis of ( )-occidentalol (c/. Vol. 8, p. 103) has resulted in a new synthesis of a-santonin (418) and its less stable /S-epimer (419) (Scheme 36). An extension of previous... 

Santonate of Soda. Put into a flask, 2 ounce.s santuninic acid, 4 fluid ounces pure caustic soda lye. and 12 fluid ounces distilled water. Heat the flask in a sand-bath or over a stove to 7(P or 80 Fahr., until the santonine solutionis complete which usually requires about half an hour then remove... 

The 13-methyl group of a-santonin has only recently been proved by X-ray crystallography to be a-oriented. Based on solvent shift data for many sesquiterpene lactones with a- and -oriented 13-methyl groups, Narayanan and Venkatasubramanian have found that an 0 -methyl resonance gives A values (d ==5cdci3 — CeHe) 0-23+0-06 p.p.m., whereas -methyl resonances give A values of 0 46 + 0-06 p.p.m. 

Startg. bromolactone hydrogenated with Pd-on-charcoal in alcohol containing 1 equivalent K-acetate as buffer dihydro-i/ -santonin. Y ca. 100%. D. A. Denton, F. J. McQuillin, and P. L. Simpson, Proc. Chem. Soc. 196A, 297. 

Ocouts with santonin in se of Ai miaia maritima, Liim.. Cryst. M.p. 203°. Soil EtOH. Spar. soL HgO. [al> — 84-3° in EtOH. 

Cannizzaro and Rossi discovered dibenzoyl. Santonin was discovered in wormseeds (known to Dioskourides and Pliny) simultaneously in 1830 by the pharmacists P. Kahler in Diisseldorf and P. Alms in Penzlin, who recommended its use in medicine. Another pharmacist, J. H. C. Oberdorffer (1786-1851) found that it is soluble in alkalis. H. Trommsdorff and W. Heldt ... 

Fig. 5 Dependence of vs. concentration of sodium dodecyl sulfate in mobile phase for investigated alkaloids. System C18W/ MeOH/water (8 2) buffered with phosphate buffer 0.01 MfL at pH 3. Em—emetine, S—santonine, Co—colchicine, C—caffeine, Y—yohimbine, L—lobeline, Q—quinine, Br brucine, St— strychnine, P—papaverine, G—glaucine. Bo—boldine.

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