First Total Synthesis of Aerucyclamide B and Macrocycle Analogs as Antimalarial and Anti-Trypanosomal Agents

First Total Synthesis of Aerucyclamide B and Macrocycle Analogs as Antimalarial and Anti-Trypanosomal Agents

Peña, S.; Scarone, L.; Medeiros, A.; Comini, M.; Stewart, L.; Yardley, V.; Albericio, F.; Serra, G.

Abstract:

Human African Trypanosomiasis (HAT) and malaria are neglected tropical diseases caused by Trypanosome and Plasmodium parasites respectively. Globally, an estimated 3.3 billion people were at risk of malaria in 2011 and 60 million people of HAT in 2009. Aerucyclamides A, B, C and D (Figure 1) were isolated from the cyanobacteria Microcystis aeruginosa PCC 7806 by Gademann and coworkers. Aerucyclamide B, displays potent and selective antiplasmodial activity against P. falciparum k1 (IC50 = 0.7μM) and aerucyclamide C is the most active against T. brucei rhodesiense (IC50 = 9.2 μM). As part of our search for antiparasitic agents, in the present work we report the total synthesis of Aerucyclamide B and the synthesis of antiparasitic cyclohexapeptides analogs. Some of the obtained products show enhanced activity compared with aerucyclamides.

Human African Trypanosomiasis (HAT) and malaria are neglected tropical diseases caused by Trypanosome and Plasmodium parasites respectively. Globally, an estimated 3.3 billion people were at risk of malaria in 2011 and 60 million people of HAT in 2009. Aerucyclamides A, B, C and D (Figure 1) were isolated from the cyanobacteria Microcystis aeruginosa PCC 7806 by Gademann and coworkers. Aerucyclamide B, displays potent and selective antiplasmodial activity against P. falciparum k1 (IC50 = 0.7μM) and aerucyclamide C is the most active against T. brucei rhodesiense (IC50 = 9.2 μM). As part of our search for antiparasitic agents, in the present work we report the total synthesis of Aerucyclamide B and the synthesis of antiparasitic cyclohexapeptides analogs. Some of the obtained products show enhanced activity compared with aerucyclamides.

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DOI: 10.5151/chempro-15bmos-BMOS2013_2013813154124

Referências bibliográficas

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Como citar:

Peña, S.; Scarone, L.; Medeiros, A.; Comini, M.; Stewart, L.; Yardley, V.; Albericio, F.; Serra, G.; "First Total Synthesis of Aerucyclamide B and Macrocycle Analogs as Antimalarial and Anti-Trypanosomal Agents", p-152-152. In: In Blucher Chemistry Proceedings, São Paulo, v. 1, n. 2, Dezembro.2013. São Paulo: Blucher, 2013.
ISSN 23184043, DOI 10.5151/chempro-15bmos-BMOS2013_2013813154124