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Solid-phase Synthesis of [4.4] Spirocyclic Oximes
Published on: February 6, 2019
Synthesis of Constrained Tetracyclic Peptides by Consecutive CEPS, CLIPS, and Oxime Ligation
Dieuwertje E Streefkerk1, Marcel Schmidt1,2, Johannes H Ippel3
1Van 't Hoff Institute for Molecular Sciences (HIMS) , Science Park 904, 1098 XH Amsterdam , The Netherlands.
Abstract:
In Nature, multicyclic peptides constitute a versatile molecule class with various biological functions. For their pharmaceutical exploitation, chemical methodologies that enable selective consecutive macrocyclizations are required. We disclose a combination of enzymatic macrocyclization, CLIPS alkylation, and oxime ligation to prepare tetracyclic peptides. Five new small molecular scaffolds and differently sized model peptides featuring noncanonical amino acids were synthesized. Enzymatic macrocyclization, followed by one-pot scaffold-assisted cyclizations, yielded 21 tetracyclic peptides in a facile and robust manner.
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