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Enantioselective synthesis and anti-parasitic properties of aporphine natural products

Abstract:
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.
Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1016/j.tet.2019.130814

Authors


More by this author
Institution:
University of Oxford
Division:
MPLS
Department:
Chemistry
Sub department:
Organic Chemistry
Oxford college:
Jesus College
Role:
Author
ORCID:
0000-0002-4149-0494


Publisher:
Elsevier
Journal:
Tetrahedron More from this journal
Volume:
76
Issue:
2
Article number:
130814
Publication date:
2019-11-25
Acceptance date:
2019-11-19
DOI:
EISSN:
1464-5416
ISSN:
0040-4020


Language:
English
Keywords:
Pubs id:
pubs:1078895
UUID:
uuid:87fd9fdd-f8a4-4003-aaf5-f039df3f82cb
Local pid:
pubs:1078895
Source identifiers:
1078895
Deposit date:
2020-01-06

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