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Synthesis of a new class of bisheterocycles via the Heck reaction of eudesmane type methylene lactones with 8-bromoxanthines

The eudesmane-type methylene lactones (isoalantolactone, alantolactone, 4,15-epoxyisoalantolactone, 2′,2′-dichloro-4H-spiro[cyclopropane-1′,4-eudesma-11(13)-en-8β,12-olide], and alantolactone) react with 8-bromoxanthines (8-bromocaffeine, 8-bromotheobromine, 8-bromo-3-butyltheobromine, 8-bromotheoph...

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Bibliographic Details
Published in:Tetrahedron 2017-05, Vol.73 (19), p.2717-2726
Main Authors: Patrushev, Sergey S., Rybalova, Tatyana V., Ivanov, Igor D., Vavilin, Valentin A., Shults, Elvira E.
Format: Article
Language:English
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Summary:The eudesmane-type methylene lactones (isoalantolactone, alantolactone, 4,15-epoxyisoalantolactone, 2′,2′-dichloro-4H-spiro[cyclopropane-1′,4-eudesma-11(13)-en-8β,12-olide], and alantolactone) react with 8-bromoxanthines (8-bromocaffeine, 8-bromotheobromine, 8-bromo-3-butyltheobromine, 8-bromotheophylline, 8-bromo-9-butyltheophylline) under Heck reaction conditions to produce the target (E)-13-(2,6-dioxo-2,3-dihydro-1H-purin-8-yl)eudesma-4(15),11(13)-dien-8β,12-olides and the subsequent endocyclic isomers - 11-(2,6-dioxo-2,3-dihydro-1H-purin-8-yl)-13-normethyleudecma-4(15)-7(11)-dien-8α,12-olides. It was revealed that the yield and product ratio depends on the reaction conditions and the structure of methylene lactone. The effectiveness of Pd(OAc)2–caffeine catalytic system has been demonstrated in this reaction. The electric eel acetylcholinesterase inhibitory activity of the eudecmanolide-xanthine hybrids was evaluated. Among the new type bisheterocycles compound 27 with butyl and 2-oxodecahydronaphtho[2,3-b]furan-3(2H)-ylidene)methyl substituents at C-7 and C-8 of the xanthine core showed moderate activity with IC50 value of 40 μM. Synthetic transformations of natural compounds. [Display omitted]
ISSN:0040-4020
1464-5416
DOI:10.1016/j.tet.2017.03.016