29347-10-2Relevant articles and documents
Metal-Free Synthesis of Oxazolidine-2,4-diones and 3,3-Disubstituted Oxindoles via ICl-Induced Cyclization
Yi, Wei,Fang, Xing-Xiao,Liu, Qing-Yun,Liu, Gong-Qing
, p. 6671 - 6681 (2019/01/04)
A metal-free method for the construction of oxazolidine-2,4-diones and oxindoles was discussed. Using iodine monochloride (ICl) as both the reaction promoter and iodide source, the iodolactonization of N-Boc acrylamides proceeded readily and provided the corresponding iodo oxazolidine-2,4-diones and oxazolidin-2-ones in good isolated yields. The obtained oxazolidine-2,4-diones can be used as key intermediates in the synthesis of toloxatone. When N-alkyl-N-arylacrylamide derivatives were subjected to the same reaction, iodocarbocyclization products 3,3-disubstituted oxindoles were obtained. The obtained oxindoles can be used as key intermediates in the synthesis of the alkaloids (±)-esermethole and (±)-physostigmine.
Inhibition of human acetyl- and butyrylcholinesterase by novel carbamates of (-)- and (+)-tetrahydrofurobenzofuran and methanobenzodioxepine
Luo, Weiming,Yu, Qian-Sheng,Kulkarni, Santosh S.,Parrish, Damon A.,Holloway, Harold W.,Tweedie, David,Shafferman, Avigdor,Lahiri, Debomoy K.,Brossi, Arnold,Greig, Nigel H.
, p. 2174 - 2185 (2007/10/03)
A new enantiomeric synthesis utilizing classical resolution provided two novel series of optically active inhibitors of cholinesterase: (-)- and (+)-O-carbamoyl phenols of tetrahydrofurobenzofuran and methanobenzodioxepine. An additional two series of (-)- and (+)-O-carbamoyl phenols of pyrroloindole and furoindole were obtained by known procedures, and their anticholinesterase actions were similarly quantified against freshly prepared human acetyl- (AChE) and butyrylcholinesterase (BChE). Both enantiomeric forms of each series demonstrated potent cholinesterase inhibitory activity (with IC50 values as low as 10 nM for AChE and 3 nM for BChE), with the exception of the (+)-O-carbamoyl phenols of pyrroloindole, which lacked activity (IC50 values > 1 μM). Based on the biological data of these four series, a structure-activity relationship (SAR) analysis was provided by molecular volume calculations. In addition, a probable transition-state model was established according to the known X-ray structure of a transition-state complex of Torpedo californica AChE-m-(N,N,N-trimethylammonio)-2,2,2-trifluoroacetophenone (TcAChE-TMTFA). This model proved valuable in explaining the enantioselectivity and enzyme subtype selectivity of each series. These carbamates are more potent than, or similarly potent to, anticholinesterases in current clinical use, providing not only inhibitors of potential clinical relevance but also pharmacological tools to define drug-enzyme binding interactions within an enzyme crucial in the maintenance of cognition and numerous systemic physiological functions in health, aging, and disease.
Catalytic asymmetric synthesis of either enantiomer of the calabar alkaloids physostigmine and physovenine
Matsuura, Takaharu,Overman, Larry E.,Poon, Daniel J.
, p. 6500 - 6503 (2007/10/03)
A potentially versatile asymmetric route to hexahydropyrrolo[2,3-b]indoles having carbon substituents at C-3a (Scheme 1) is demonstrated through enantioselective total syntheses of the Calabar alkaloids (-)physostigmine (2), (-)-physovenine (10), and their enantiomers. The synthesis of enantiopure (-)physostigmine proceeds from commercially available 2-butyn-1-ol (11) and N-methyl-p-anisidine (15) in 15-20% overall yield by way of eight isolated and purified intermediates. The central step is catalytic asymmetric Heck cyclization of (Z)-2-methyl-2-butenanilide 17 to-form oxindole aldehyde (S)-19 in 84% yield and 95% ee.
