Solid Phase Synthesis of Hexapeptides and Solution Macrocyclization to Obtain Antiparasitic Agents

Solid Phase Synthesis of Hexapeptides and Solution Macrocyclization to Obtain Antiparasitic Agents

Fagundez, Catherine; Sellanes, Diver; Medeiros, Andrea; Comini, Marcelo; Stewart, Lindsay; Yardley, Vanessa; Serra, Gloria

Abstract:

Hapalociclamide, Aeruciclamides,and Microciclamides are bioactive hexacyclopeptides alternating in hydrophobic and hydrophilic (Ser, Thr and Cys) amino acids. The side chains of these polar amino acids are heterocyclized to form azoles. Seeking to further explore their biological activity, our group began a program to develop a route to macrocyclic analogs of natural products with antimalarial or antitrypanosomal activity. The long time required for solution synthesis of peptides encouraged us to explore the solid phase peptide synthesis (SPPS). This methodology diminishes the reaction time and the necessary amount of peptides could be obtained in excellent yields and purities. In the present work the solid phase synthesis of different hexapeptides using 2Cl-trityl and Wang resins, the macrocyclization reactions, the studies on cyclodehydration and the biological evaluation of the obtained compounds will be presented.

Hapalociclamide, Aeruciclamides,and Microciclamides are bioactive hexacyclopeptides alternating in hydrophobic and hydrophilic (Ser, Thr and Cys) amino acids. The side chains of these polar amino acids are heterocyclized to form azoles. Seeking to further explore their biological activity, our group began a program to develop a route to macrocyclic analogs of natural products with antimalarial or antitrypanosomal activity. The long time required for solution synthesis of peptides encouraged us to explore the solid phase peptide synthesis (SPPS). This methodology diminishes the reaction time and the necessary amount of peptides could be obtained in excellent yields and purities. In the present work the solid phase synthesis of different hexapeptides using 2Cl-trityl and Wang resins, the macrocyclization reactions, the studies on cyclodehydration and the biological evaluation of the obtained compounds will be presented.

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DOI: 10.5151/chempro-15bmos-BMOS2013_2013822155639

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Como citar:

Fagundez, Catherine; Sellanes, Diver; Medeiros, Andrea; Comini, Marcelo; Stewart, Lindsay; Yardley, Vanessa; Serra, Gloria; "Solid Phase Synthesis of Hexapeptides and Solution Macrocyclization to Obtain Antiparasitic Agents", p-198-198. 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_2013822155639