- Stereoselective total synthesis of (S)- and (R)-nuciferine using benzyne chemistry
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Total syntheses of (S)- and (R)-nuciferine were accomplished through approach involving diastereoselective reaction between a chiral dihydroisoquinoline enamide and 2-(trimethylsilyl)phenyl trifluoromethanesulfonate promoted by CsF, affording a separable mixture of diastereoisomers, which provided (S)- and (R)-nuciferine via simple and efficient transformations.
- Casagrande, Gleison A.,Deflon, Victor M.,Martins, Gabriel R.,Oliveira-Silva, Diogo,Perecim, Givago P.,Pinto, Leandro M. C.,Raminelli, Cristiano
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- Synthesis and structure-Activity relationship of nuciferine derivatives as potential acetylcholinesterase inhibitors
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Acetylcholinesterase inhibitors (AChEIs) are currently the best available pharmacotherapy for Alzheimer patients, but because of bioavailability issues, there is still great interest in discovering better AChEIs. The aporphine alkaloid is an important class of natural products, which shows diverse biological activity, such as acetylcholinesterase inhibitory activity. To find new lead AChEIs compounds, eight aporphine alkaloids were synthesized by O-dealkylation, N-dealkylation, and ring aromatization reactions using nuciferine as raw material. The anti-Acetylcholinesterase activity of synthesized compounds was measured using modified Ellman's method. The results showed that some synthesized compounds exhibited higher affinity to AChE than the parent compound nuciferine. Among these compounds, 1,2-dihydroxyaporphine (2) and dehydronuciferine (5) were the most active compounds (IC50 = 28 and 25 μg/mL, respectively). Preliminary analysis of structure-Activity relationships suggested that aromatization of the C ring, the presence of the alkoxyl group at C1 and the hydroxy group at C2 position as well as the alkyl substituent at the N atom were favorable to the acetylcholinesterase inhibition. Molecular docking was also applied to predict the binding modes of compounds 1, 2, and 9 into the huperzine A binding site of AChE.
- Yang, Zhongduo,Song, Zhuwen,Xue, Weiwei,Sheng, Jie,Shu, Zongmei,Shi, Yin,Liang, Jibei,Yao, Xiaojun
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p. 3178 - 3186
(2014/05/06)
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- Aporphine alkaloid synthesis and diversification via direct arylation
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Palladium-catalyzed direct arylation of aryl chlorides, bromides and iodides has been applied to the preparation of new aporphine analogues including C2-substituted aporphines by reaction with benzodioxole, pyridine N-oxide and pyrazine N-oxide. Successful application of direct arylation in these diversification reactions highlights its utility not only in convergent, but also in divergent synthesis. We also describe enantioselective syntheses of (R)-nornuciferine and (R)-nuciferine employing a catalytic asymmetric transfer hydrogenation in high yield and excellent enantiomeric excess. Wiley-VCH Verlag GmbH & Co. KGaA, 2007.
- Lafrance, Marc,Blaquiere, Nicole,Fagnou, Keith
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p. 811 - 825
(2008/02/12)
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