title: Decarboxylative Peptide Macrocyclization through Photoredox Catalysis.
abstract: A method for the decarboxylative macrocyclization of peptides bearing N-terminal Michael acceptors has been developed. This synthetic method enables the efficient synthesis of cyclic peptides containing γ-amino acids and is tolerant of functionalities present in both natural and non-proteinogenic amino acids. Linear precursors ranging from 3 to 15 amino acids cyclize effectively under this photoredox method. To demonstrate the preparative utility of this method in the context of bioactive molecules, we synthesized COR-005, a somatostatin analogue that is currently in clinical trials.
authors.affiliation: Merck Center for Catalysis at Princeton University, Washington Road, Princeton, NJ, 08544, USA.
authors.forename: Stefan J
authors.initials: SJ
authors.lastname: McCarver
authors.affiliation: Bristol-Myers Squibb, Route 206 & Province Line Road, Princeton, NJ, 08543, USA.
authors.forename: Jennifer X
authors.initials: JX
authors.lastname: Qiao
authors.affiliation: Bristol-Myers Squibb, Route 206 & Province Line Road, Princeton, NJ, 08543, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Carpenter
authors.affiliation: Bristol-Myers Squibb, Route 206 & Province Line Road, Princeton, NJ, 08543, USA.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Borzilleri
authors.affiliation: Bristol-Myers Squibb, Route 206 & Province Line Road, Princeton, NJ, 08543, USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Poss
authors.affiliation: Bristol-Myers Squibb, Route 206 & Province Line Road, Princeton, NJ, 08543, USA.
authors.forename: Martin D
authors.initials: MD
authors.lastname: Eastgate
authors.affiliation: Bristol-Myers Squibb, Route 206 & Province Line Road, Princeton, NJ, 08543, USA.
authors.forename: Michael M
authors.initials: MM
authors.lastname: Miller
authors.affiliation: Merck Center for Catalysis at Princeton University, Washington Road, Princeton, NJ, 08544, USA.
authors.forename: David W C
authors.initials: DW
authors.lastname: MacMillan
mesh_terms: D002384:Catalysis; D003500:Cyclization; D003653:Decarboxylation; D046911:Macromolecular Substances / Q000138:chemical synthesis / Q000737:chemistry; D015394:Molecular Structure; D010084:Oxidation-Reduction; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry; D055668:Photochemical Processes
chemical_list: D046911:Macromolecular Substances; D010455:Peptides
keywords: Michael addition; decarboxylation; macrocycles; peptides; photoredox catalysis