Foldamer-templated catalysis of macrocycle formation

Abstract

Macrocycles made easy Macrocycles, which are molecules with large rings of 12 or more atoms, are challenging to produce by intramolecular cyclization because floppy ends tend to join up with another molecule rather than fold back on themselves. Girvin et al. identified a foldamer—a short, structured peptide—that can cyclize floppy, dialdehyde substrates through a templated aldol condensation (see the Perspective by Gutiérrez Collar and Gulder). Variation of the residues within the foldamer suggests that its helical structure helps position amine functional groups crucial for catalysis. The authors prepared molecules with a wide range of ring sizes and developed a synthesis for robustol, a macrocycle natural product with a 22-member ring. Science , this issue p. 1528 ; see also p. 1454