Synthesis of a Macrocyclic Marine Natural Product Analog

Synthesis of a Macrocyclic Marine Natural Product Analog

Serra, Gloria; Peña, Stella; Scarone, Laura; Manta, Eduardo

Abstract:

Marine natural products Aerucyclamide B (1) and Dendroamide A (2), Figure 1, are bioactive hexacyclopeptides alternating in hydrophobic and hydrophilic (Thr and Cys) amino acids. The side chains of these polar amino acids are heterocyclized to form azole rings. The oxidation state of heterocyclic rings can enforce different conformations on macrocycles and this has been shown to result in very different affinities for metal ions and consequently different biological activity. As part of our search for candidates for antiparasitic new drugs, we embarked in the synthesis of macrocycles analogs of these marine natural products. In the present work, we present the synthesis of the macrocycle 3 which is more stable, cheaper and easier to prepare than Aerucyclamides.

Marine natural products Aerucyclamide B (1) and Dendroamide A (2), Figure 1, are bioactive hexacyclopeptides alternating in hydrophobic and hydrophilic (Thr and Cys) amino acids. The side chains of these polar amino acids are heterocyclized to form azole rings. The oxidation state of heterocyclic rings can enforce different conformations on macrocycles and this has been shown to result in very different affinities for metal ions and consequently different biological activity. As part of our search for candidates for antiparasitic new drugs, we embarked in the synthesis of macrocycles analogs of these marine natural products. In the present work, we present the synthesis of the macrocycle 3 which is more stable, cheaper and easier to prepare than Aerucyclamides.

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DOI: 10.5151/chempro-14bmos-R0079-1

Referências bibliográficas

• [1] 1 a) Portmann, C.; Blom, J. F.; Gademann, K.; Jüttner, F. J. Nat. Prod. 2008, 71, 1193. b) Portmann, C., Blom, J. F., Kaiser, M., Brun, R., Jüttner, F. Gademann, K. J. Nat. Prod. 2008, 71, 1891.
• [2] 2 Ogino, J.; Moore, R. E.; Patterson, G. M.; Smith, C. D. J. Nat. Prod. 1996, 59, 581.
• [3] 3 a) Sellanes, D.; Campot, F.; Nuñez, I.; Lin, G.; Espósito, P.; Saldaña, J.; Domínguez, L.; Manta, E.; Serra, G. Tetrahedron 2010, 66, 5384. b) Scarone, L.; Fajardo, J.; Saldaña, J.; Domínguez, L.; Espósito, P.; Dematteis, S.; Wipf, P.; Manta, E.; Serra, G. Lett. Drug, Des. And Disc. 2009, 6, 413.

Como citar:

Serra, Gloria; Peña, Stella; Scarone, Laura; Manta, Eduardo; "Synthesis of a Macrocyclic Marine Natural Product Analog", p-79-79. In: In Blucher Chemistry Proceedings, São Paulo, v. 1, n. 1, Setembro.2013. São Paulo: Blucher, 2013.
ISSN 23184043, DOI 10.5151/chempro-14bmos-R0079-1