Acidic isomerization of alantolactone derivatives

Abstract

A series of derivatives of the natural sesquiterpene lactones alantolactone (1) and isoalantolactone (2) was prepared. The α-methylene-γ-lactone moiety was retained in the structures of these for further modifications using reactions that affected exclusively the nonconjugated double bonds of the decalin ring.The great potential biological and pharmacological activities of natural sesquiterpene lactones are responsible for the interest in developing this area of chemistry [1,2]. The most promising direction is the chemical modification of compounds isolated from natural sources in order to prepare substances with new properties. Certain natural sesquiterpene lactones have been used as effective medicinal preparations (for example, the antitumor preparation Arglabin [3]).The goal of the present work was to prepare a series of derivatives based on the natural sesquiterpene lactones alantolactone (1) and isoalantolactone (2) in the structures of which the α-methylene-γ-lactone moiety was retained for further modifications. This was achieved using reactions that affected exclusively the nonconjugated double bonds of the decalin ring.A mixture of lactones 1 and 2 (~1:1 ratio) was isolated from roots of Inula helenium L. (Asteraceae) by a method consisting of extraction of the ground raw material with CHCl 3 and subsequent chromatography over a column of SiO 2 . Fractions containing this mixture were evaporated and crystallized (2-3 times) from aqueous CH 3 OH (70%) to afford about 25% (of the total content of the extract) of pure 2. The isomers were further separated over a column of SiO 2 impregnated with AgNO 3 (5%) with gradient elution by benzene in light petroleum ether. The compounds isolated by chromatography over the column impregnated with Ag contained an impurity of Ag (2-5% according to elemental analysis) that was removed by passing their benzene solution over a layer of neutral Al 2 O 3 (activity I). The resulting compounds were identical to those in the literature [4].It is well known that olefins can undergo acidic isomerization to form intermediates and transition-state carbonium ions in which prototropic and skeletal rearrangements are observed. Therefore, we investigated the reactions of the alantolactone derivatives with acids.Alantolactone (1) is stable to acids (under drastic conditions the reaction mixture polymerizes) according to the literature [5] and our data.Shifts of the exocyclic double bond in the decalin ring of 2 that occur in the presence of acids have been reported [6]. This formed a mixture of the thermodynamically more favorable isomeric trisubstituted olefins that contain an endocyclic double bond between C-4 and C-5 (3) or C-3 and C-4. The ratio of products depends on the acid used (2:1 for methanesulfonic acid in trifluoroethanol [5] and 1:3 in formic acid [7]). We found the conditions for selective isomerization of 2 into 3. The PMR spectrum of 3 contained a singlet for the methyl on the double bond (1.60 ppm) instead of signals for the exomethylene protons on C-15. The 13 C NMR...

Mosquito Larvicidal Constituents from the Ethanol Extract ofInula racemosaHook. f. Roots againstAedes albopictus

“…13 C-NMR (125 MHz, CDCl 3 ) (ppm): 170.5 (C-12), 141.8 (C-11), 120.5 (C-13), 76.6 (C-8), 58.5 (C-4), 50.7 (C-15), 44.1 (C-5), 41.8 (C-1), 41.3 (C-9), 40.3 (C-7), 35.3 (C-3), 34.2 (C-10), 23.1 (C-6), 20.3 (C-2), 18.6 (C-14). The data matched previous report[23].…”

Natural sesquiterpenoids

“…301 The acid catalysed isomerisation of several alantolactone derivatives has been studied. 302 A rearranged eudesmane sesquiterpenoid 317, with a novel bicyclic ring system, has been obtained from Jasonia montana. 303 This compound was named jasomontanone, but unfortunately a norsesquiterpene, also isolated from this species, had previously been given the same name.…”

Metabolism Analysis of Alantolactone and Isoalantolactone in Rats by Oral Administration

“…In addition, six relevant lactones 3,4-dehydroalantolactone (3), 5 ,6 -epoxyalantolactone (4), 6-hydroxyl alantolactone (5), 4-hydroxymethyl isolalantolactone (6), 11-carboxyl alantolactone (7), and 11-carboxyl alantolactone (8) were obtained. Their structures were confirmed by MS and NMR determination [14][15][16][17][18][19].…”