title: An unusual intramolecular hetero-Diels-Alder cycloaddition.
abstract: A new reaction of erythronolides, an intramolecular hetero-Diels-Alder, has been discovered. Heated aqueous alcoholic solutions of ABT-773 (1) and its cis isomer (3) convert slowly to cycloadducts 2 and 4, respectively. Optimal reaction conditions, mechanistic studies supported by molecular modeling, and biological activity data are reported. Single-crystal X-ray structures for both adducts 2 and 4 have been obtained.
authors.affiliation: Abbott Laboratories, 1401 Sheridan Road, North Chicago, IL 60064-6290, USA. eric.stoner@abbott.com
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Stoner
authors.forename: Michael S
authors.initials: MS
authors.lastname: Allen
authors.forename: Alan C
authors.initials: AC
authors.lastname: Christesen
authors.forename: Rodger F
authors.initials: RF
authors.lastname: Henry
authors.forename: L Steven
authors.initials: LS
authors.lastname: Hollis
authors.forename: Robert
authors.initials: R
authors.lastname: Keyes
authors.forename: Ian
authors.initials: I
authors.lastname: Marsden
authors.forename: Tamara C
authors.initials: TC
authors.lastname: Rehm
authors.forename: Sandeep G
authors.initials: SG
authors.lastname: Shiroor
authors.forename: Niru B
authors.initials: NB
authors.lastname: Soni
authors.forename: Kent D
authors.initials: KD
authors.lastname: Stewart
mesh_terms: D002384:Catalysis; D018360:Crystallography, X-Ray; D003500:Cyclization; D004917:Erythromycin / Q000031:analogs & derivatives* / Q000737:chemistry*; D048628:Ketolides / Q000737:chemistry*; D008968:Molecular Conformation; D015394:Molecular Structure; D013237:Stereoisomerism
chemical_list: D048628:Ketolides; D004917:Erythromycin; C405499:cethromycin