title: Ring-opening and ring-closing reactions of a shikimic acid-derived substrate leading to diverse small molecules.
abstract: An epoxide derived from (-)-shikimic acid was attached to a solid support and used to synthesize over 5000 diverse small molecules. Key transformations include a Lewis acid-catalyzed epoxide opening with amines and an intramolecular Heck reaction with aryl iodides. Compounds derived from this pathway were printed onto small-molecule microarrays and screened for binding to proteins. Compounds that bound to Aurora A kinase were characterized using surface plasmon resonance.
authors.affiliation: Broad Institute of Harvard and MIT, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA.
authors.forename: Hua
authors.initials: H
authors.lastname: Miao
authors.forename: John A
authors.initials: JA
authors.lastname: Tallarico
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Hayakawa
authors.forename: Karl
authors.initials: K
authors.lastname: Münger
authors.forename: Jay L
authors.initials: JL
authors.lastname: Duffner
authors.forename: Angela N
authors.initials: AN
authors.lastname: Koehler
authors.forename: Stuart L
authors.initials: SL
authors.lastname: Schreiber
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Lewis
mesh_terms: D064127:Aurora Kinases; D003500:Cyclization; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D012765:Shikimic Acid / Q000737:chemistry*; D013379:Substrate Specificity; D020349:Surface Plasmon Resonance
chemical_list: D012765:Shikimic Acid; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases