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

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Synthesis of a new class of bisheterocycles via the Heck reaction of eudesmane type methylene lactones with 8-bromoxanthines. / Patrushev, Sergey S.; Rybalova, Tatyana V.; Ivanov, Igor D. et al.

In: Tetrahedron, Vol. 73, No. 19, 11.05.2017, p. 2717-2726.

Research output: Contribution to journal › Article › peer-review

BibTeX

@article{2303d5b5745047b991af62f616061c3d,

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

abstract = "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.",

keywords = "Acetylcholinesterase inhibitors, Heck reaction, Isoalantolactone, Sesquiterpene lactones, Xanthine, PURINES, XANTHINE DERIVATIVES, ISOALANTOLACTONE, ALANTOLACTONE, SESQUITERPENE LACTONES, INHIBITION, ACETYLCHOLINESTERASE, MONOAMINE-OXIDASE-B, TRANSFORMATIONS, WATER",

author = "Patrushev, {Sergey S.} and Rybalova, {Tatyana V.} and Ivanov, {Igor D.} and Vavilin, {Valentin A.} and Shults, {Elvira E.}",

year = "2017",

month = may,

day = "11",

doi = "10.1016/j.tet.2017.03.016",

language = "English",

volume = "73",

pages = "2717--2726",

journal = "Tetrahedron",

issn = "0040-4020",

publisher = "Elsevier",

number = "19",

}

RIS

TY - JOUR

T1 - Synthesis of a new class of bisheterocycles via the Heck reaction of eudesmane type methylene lactones with 8-bromoxanthines

AU - Patrushev, Sergey S.

AU - Rybalova, Tatyana V.

AU - Ivanov, Igor D.

AU - Vavilin, Valentin A.

AU - Shults, Elvira E.

PY - 2017/5/11

Y1 - 2017/5/11

N2 - 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.

AB - 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.

KW - Acetylcholinesterase inhibitors

KW - Heck reaction

KW - Isoalantolactone

KW - Sesquiterpene lactones

KW - Xanthine

KW - PURINES

KW - XANTHINE DERIVATIVES

KW - ISOALANTOLACTONE

KW - ALANTOLACTONE

KW - SESQUITERPENE LACTONES

KW - INHIBITION

KW - ACETYLCHOLINESTERASE

KW - MONOAMINE-OXIDASE-B

KW - TRANSFORMATIONS

KW - WATER

UR - http://www.scopus.com/inward/record.url?scp=85016418486&partnerID=8YFLogxK

U2 - 10.1016/j.tet.2017.03.016

DO - 10.1016/j.tet.2017.03.016

M3 - Article

AN - SCOPUS:85016418486

VL - 73

SP - 2717

EP - 2726

JO - Tetrahedron

JF - Tetrahedron

SN - 0040-4020

IS - 19

ER -

ID: 10267465