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

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

Journal

Tetrahedron
ISSN: 0040-4020

Output data

Year: 2017, Volume: 73, Number: 19, Pages: 2717-2726 Pages count : DOI: 10.1016/j.tet.2017.03.016

Tags

Sesquiterpene lactones; Isoalantolactone; Xanthine; Heck reaction; Acetylcholinesterase inhibitors

Authors

Patrushev Sergey S. ^1,2 , Rybalova Tatyana V. ^1,2 , Ivanov Igor D. ³ , Vavilin Valentin A. ^2,3 , Shults Elvira E. ^1,2

Affiliations

1	(Данные Web of science) Russian Acad Sci, Novosibirsk Inst Organ Chem, Siberian Branch, Lavrentyev Ave 9, Novosibirsk 630090, Russia
2	(Данные Web of science) Novosibirsk State Univ, Pirogova St 1, Novosibirsk 630090, Russia
3	(Данные Web of science) Inst Mol Biol & Biophys, Timakova St 2-12, Novosibirsk 630117, Russia

The eudesmane-type methylene lactones (isoalantolactone, alantolactone, 4,15-epoxyisoalantolactone, 2',2'-dichloro-4H-spirolcyclopropane-1',4-eudesma-11(13)-en-8 beta,12-olidel, 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-8 beta,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-8 alpha,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 M. (C) 2017 Elsevier Ltd. All rights reserved.

Patrushev S.S. , Rybalova T.V. , Ivanov I.D. , Vavilin V.A. , Shults E.E.
Synthesis of a new class of bisheterocycles via the Heck reaction of eudesmane type methylene lactones with 8-bromoxanthines
Tetrahedron. 2017. V.73. N19. P.2717-2726. DOI: 10.1016/j.tet.2017.03.016 WOS Scopus РИНЦ

Published print:

May 1, 2017

Web of science	WOS:000400532000001
Scopus	2-s2.0-85016418486
Elibrary	29495948
OpenAlex	W2596244944