Enantioselective synthesis and anti-parasitic properties of aporphine natural products

Autor(es)

Pieper, Pauline ; McHugh, Eliza ; Amaral, Maiara ; Tempone, Andre G. ; Anderson, Edward A.

• Tipo de documento: Artigo Científico
• Fonte: Tetrahedron; v. 76, n. 2, p. 8-pg., 2020-01-10.

Resumo

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. (C) 2019 Elsevier Ltd. All rights reserved. (AU)

• Processo FAPESP: 18/25128-3 - Otimização de protótipos naturais como novos candidatos terapêuticos para Leishmaniose Visceral
• Beneficiário: Maiara Amaral de Oliveira
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 18/10279-6 - Seleção e Otimização de Novos Candidatos a Fármacos para Leishmaniose e Doença de Chagas
• Beneficiário: André Gustavo Tempone Cardoso
• Modalidade de apoio: Auxílio à Pesquisa - Regular