title: A new and useful method for the macrocyclization of linear peptides.
abstract: A new and useful procedure for the macrocyclization of linear peptides is described. The natural amino acid side chains of tyrosine (phenol), lysine (alkylamine), and histidine (imidazole) react in an intramolecular fashion with a pendent pyridine-N-oxide-carboxamide, which is selectively activated by the phosphonium salt, PyBroP. The reaction is mild, rapid, and efficient with a potentially large substrate scope. Multiple examples are provided with full characterization and analyses, including a novel aza-variant of the C-O-D ring system of vancomycin.
authors.affiliation: CVMED Medicinal Chemistry, Pfizer Inc., Eastern Point Road, Groton, Connecticut 06340, USA. allyn.t.londregan@pfizer.com
authors.forename: Allyn T
authors.initials: AT
authors.lastname: Londregan
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Farley
authors.forename: Chris
authors.initials: C
authors.lastname: Limberakis
authors.forename: Patrick B
authors.initials: PB
authors.lastname: Mullins
authors.forename: David W
authors.initials: DW
authors.lastname: Piotrowski
mesh_terms: D002625:Chemistry, Organic / Q000379:methods*; D003500:Cyclization; D006639:Histidine / Q000737:chemistry; D008239:Lysine / Q000737:chemistry; D008958:Models, Molecular; D015394:Molecular Structure; D010455:Peptides / Q000737:chemistry*; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry; D014640:Vancomycin / Q000737:chemistry
chemical_list: D010455:Peptides; D010456:Peptides, Cyclic; D006639:Histidine; D014640:Vancomycin; D008239:Lysine