Zebediah C Girvin1, Mary Katherine Andrews1, Xinyu Liu1, Samuel H Gellman2. 1. Department of Chemistry, University of Wisconsin-Madison, Madison, WI, USA. 2. Department of Chemistry, University of Wisconsin-Madison, Madison, WI, USA. gellman@chem.wisc.edu.
Abstract
Macrocycles, compounds containing a ring of 12 or more atoms, find use in human medicine, fragrances, and biological ion sensing. The efficient preparation of macrocycles is a fundamental challenge in synthetic organic chemistry because the high entropic cost of large-ring closure allows undesired intermolecular reactions to compete. Here, we present a bioinspired strategy for macrocycle formation through carbon-carbon bond formation. The process relies on a catalytic oligomer containing α- and β-amino acid residues to template the ring-closing process. The α/β-peptide foldamer adopts a helical conformation that displays a catalytic primary amine-secondary amine diad in a specific three-dimensional arrangement. This catalyst promotes aldol reactions that form rings containing 14 to 22 atoms. Utility is demonstrated in the synthesis of the natural product robustol.
Macrocycles, compounds containing a ring of 12 or more atoms, find use in n class="Species">human medicine, fragrances, and biological ion sensing. The efficient preparation of macrocycles is a fundamental challenge in synthetic organic chemistry because the high entropic cost of large-ring closure allows undesired intermolecular reactions to compete. Here, we present a bioinspired strategy for macrocycle formation through n class="Chemical">carbon-carbon bond formation. The process relies on a catalytic oligomer containing α- and β-amino acid residues to template the ring-closing process. The α/β-peptide foldamer adopts a helical conformation that displays a catalytic primary amine-secondary aminediad in a specific three-dimensional arrangement. This catalyst promotes aldol reactions that form rings containing 14 to 22 atoms. Utility is demonstrated in the synthesis of the natural product robustol.
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