title: Macrocyclizations for medicinal chemistry: synthesis of druglike macrocycles by high-concentration Ullmann coupling.
abstract: Conditions have been identified for the efficient Ullmann macrocyclization of phenol and imidazole nucleophiles with aryl iodides at high reaction concentrations of up to 100 mM and using 5-10 mol % loading of an inexpensive copper catalyst. A range of substitution patterns and ring sizes are tolerated, and the method has been exemplified by the synthesis of a set of druglike macrocycles.
authors.affiliation: Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
authors.forename: James C
authors.initials: JC
authors.lastname: Collins
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Farley
authors.forename: Chris
authors.initials: C
authors.lastname: Limberakis
authors.forename: Spiros
authors.initials: S
authors.lastname: Liras
authors.forename: David
authors.initials: D
authors.lastname: Price
authors.forename: Keith
authors.initials: K
authors.lastname: James
mesh_terms: D060326:Chemistry Techniques, Synthetic; D002626:Chemistry, Pharmaceutical; D003500:Cyclization; D015195:Drug Design; D006639:Histidine / Q000737:chemistry; D007093:Imidazoles / Q000737:chemistry; D047028:Macrocyclic Compounds / Q000138:chemical synthesis* / Q000737:chemistry*; D010636:Phenols / Q000737:chemistry; D014443:Tyrosine / Q000737:chemistry
chemical_list: D007093:Imidazoles; D047028:Macrocyclic Compounds; D010636:Phenols; D014443:Tyrosine; D006639:Histidine