Ring-opening and ring-closing reactions of a shikimic acid-derived substrate leading to diverse small molecules.
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.
Miao
Hua
H
Broad Institute of Harvard and MIT, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA.
Tallarico
John A
JA
Hayakawa
Hiroyuki
H
Münger
Karl
K
Duffner
Jay L
JL
Koehler
Angela N
AN
Schreiber
Stuart L
SL
Lewis
Timothy A
TA
D064127:Aurora Kinases; D003500:Cyclization; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D012765:Shikimic Acid / Q000737:chemistry*; D013379:Substrate Specificity; D020349:Surface Plasmon Resonance
D012765:Shikimic Acid; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases