Syntheses of tetrahydrofurobenzofurans and dihydromethanobenzodioxepines from 5-hydroxy-3-methyl-3H-benzofuran-2-one. Rearrangement and ring expansion under reductive conditions on treatment with hydrides.
5-Hydroxy-3-methyl-3H-benzofuran-2-one, 5, easily obtained from pyruvic acid and 1,4-cyclohexanedione, was used as a starting material to prepare (+/-)-5-hydroxy-3a-methyl-2,3,3a,8a-tetrahydro-furo[2,3-b]benzofuran, 10, and (+/-)-7-hydroxy-5-methyl-4,5-dihydro-2,5-methano-1,3-benzodioxepine, 14. Reduced reactivity relative to 5-hydroxy-3-methoxycarbonylmethylene-3-methyl-3H-benzofuran-2-one, 6, was preliminarily studied. Meanwhile, a plausible mechanism with regard to the formation of 10 and 14, which included cyclization, rearrangement, and ring expansion of hemiacetal, 15, is proposed. Specific carbamates of phenols, 10 and 14, have shown impressive inhibitory activities against human acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) ex vivo.
Luo
Weiming
W
Drug Design & Development Section, Laboratory of Neurosciences, Intramural Research Program, National Institute on Aging, National Institutes of Health, 5600 Nathan Shock Drive, Baltimore, Maryland 21224, USA.
Yu
Qian-Sheng
QS
Holloway
Harold W
HW
Parrish
Damon
D
Greig
Nigel H
NH
Brossi
Arnold
A
D001572:Benzofurans / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002802:Cholinesterases / Q000378:metabolism; D006358:Hot Temperature; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D010082:Oxepins / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology
C504697:5-hydroxy-3-methyl-3H-benzofuran-2-one; D001572:Benzofurans; D002800:Cholinesterase Inhibitors; D010082:Oxepins; D002802:Cholinesterases; C105430:benzofuran