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Foldamer-templated catalysis of macrocycle formation.

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 ?- and ?-amino acid residues to template the ring-closing process. The ?/?-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.

SUBMITTER: Girvin ZC

PROVIDER: S-EPMC7956107 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Foldamer-templated catalysis of macrocycle formation.

Girvin Zebediah C ZC Andrews Mary Katherine MK Liu Xinyu X Gellman Samuel H SH

Science (New York, N.Y.) 20191219 6472

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 ...[more]

PMID: 31857487

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