- Enantioselective synthesis and anti-parasitic properties of aporphine natural products
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Chagas disease and visceral leishmaniasis are neglected protozoan diseases with significant impact in developing countries. Due to the limited number and toxicity of current therapies, new drug leads are urgently needed. In this work, four aporphine natural products were synthesized using an enantioselective, modular and convergent strategy, comprising eight steps in the longest linear sequence; key steps included Bischler-Napieralski cyclization/Noyori asymmetric reduction to construct the tetrahydroisoquinolines, and palladium-catalyzed arylation to close the C ring. Norglaucine, nordicentrine and dicentrine showed promising bioactivity against T. cruzi and L. infantum, suggesting potential for further development of these scaffolds as antiparasitic agents.
- Amaral, Maiara,Anderson, Edward A.,McHugh, Eliza,Pieper, Pauline,Tempone, Andre G.
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- In vitro functional evaluation of isolaureline, dicentrine and glaucine enantiomers at 5-HT2 and α1 receptors
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Compounds with activity at serotonin (5-hydroxytryptamine) 5-HT2 and α1 adrenergic receptors have potential for the treatment of central nervous system disorders, drug addiction or overdose. Isolaureline, dicentrine and glaucine enantiomers were synthesized, and their in vitro functional activities at human 5-HT2 and adrenergic α1 receptor subtypes were evaluated. The enantiomers of isolaureline and dicentrine acted as antagonists at 5-HT2 and α1 receptors with (R)-isolaureline showing the greatest potency (pKb?=?8.14 at the 5-HT2C receptor). Both (R)- and (S)-glaucine also antagonized α1 receptors, but they behaved very differently to the other compounds at 5-HT2 receptors: (S)-glaucine acted as a partial agonist at all three 5-HT2 receptor subtypes, whereas (R)-glaucine appeared to act as a positive allosteric modulator at the 5-HT2A receptor.
- Heng, Hui Li,Chee, Chin Fei,Thy, Chun Keng,Tee, Jia Ti,Chin, Sek Peng,Herr, Deron R.,Buckle, Michael J. C.,Paterson, Ian C.,Doughty, Stephen W.,Abd. Rahman, Noorsaadah,Chung, Lip Yong
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p. 132 - 138
(2018/10/15)
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- Discovery of Aporphine Analogues as Potential Antiplatelet and Antioxidant Agents: Design, Synthesis, Structure–Activity Relationships, Biological Evaluations, and in silico Molecular Docking Studies
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To explore the potential of aporphine alkaloids, a novel series of functionalized aporphine analogues with alkoxy (OCH3, OC2H5, OC3H7) functional groups at C1/C2 of ring A and an acyl (COCH3/sub
- Sharma, Vashundhra,Jaiswal, Pradeep K.,Kumar, Surendra,Mathur, Manas,Swami, Ajit K.,Yadav, Dharmendra K.,Chaudhary, Sandeep
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p. 1817 - 1832
(2018/09/10)
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- The palladium-catalyzed preparation of condensed tetracyclic heterocycles and their application to the synthesis of rac-mangochinine
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Dihydroisoquinoline derivatives and their analogues, prepared by the Bischler-Napieralsky reaction, were converted to their indole-fused derivatives. Scope and limitations of the palladium-catalyzed reaction, proceeding through the tautomeric enamine forms of these compounds, were studied and the process was extended to the preparation of racemic mangochinine. Georg Thieme Verlag Stuttgart.
- Vincze, Zoltan,Biro, A. Beatrix,Csekei, Marton,Timari, Geza,Kotschy, Andras
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p. 1375 - 1385
(2007/10/03)
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