Preparation of penta-azole containing cyclopeptides: challenges in macrocyclization

• Published in: Tetrahedron Vol. 63; no. 39; pp. 9862 - 9870
• Main Authors: Hernández, Delia, Riego, Estela, Francesch, Andrés, Cuevas, Carmen, Albericio, Fernando, Álvarez, Mercedes
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 24-09-2007; Elsevier B.V
• Subjects: Compostos heterocíclics; Heterocyclic compounds; Natural products; Organic synthesis; Peptides; Productes naturals; Pèptids; Síntesi orgànica
• ISSN: 0040-4020; 1464-5416
• DOI: 10.1016/j.tet.2007.06.103

Herein is described the synthesis of several analogs of the natural product IB-01211 from concatenated azoles, via a biomimetic pathway based on cyclization–oxidation of serine containing peptides combined with the Hantzsch synthesis. The macrocyclization of rigid peptide compounds
1 and
2 to give IB-01211 and its epimer
12b was explored, and the results are compared here to those previously obtained for the macrocyclization of more flexible structures in the syntheses of YM-216391, telomestatin, and IB-01211. Lastly, the preliminary results of anti-tumor activity screening of the synthesized analogs are discussed.
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