Chemoenzymatic construction of a four-component Ugi combinatorial library.
The chemoenzymatic preparation of a nine-member Ugi condensation library is described. The carboxylic acid and amine precursors are based on 3-hydroxybutyrate and 4-amino-1-butanol, respectively, and have been acylated selectively using a variety of acyl donors catalyzed by porcine pancreatic lipase. The enzyme is selective for the hydroxyl functionalities on both precursors, thereby yielding 3-acyl-butyric acid and 4-amino-1-acyl compounds. These enzymatically generated derivatives were then subjected to a four-component Ugi condensation reaction in the presence of acetaldehyde and methyl isocyanoacetate. Isolated yields of the alpha-(acylamino)amide Ugi products ranged from 72-95%. The inherent chemoselectivity of enzymatic catalysis may play an increasingly important role in expanding the structural diversity that can be achieved by chemical multicomponent condensation reactions.
Liu
X C
XC
Department of Chemical Engineering, Rensselaer Polytechnic Institute, Troy, NY 12180, USA.
Clark
D S
DS
Dordick
J S
JS
D020155:3-Hydroxybutyric Acid / Q000138:chemical synthesis*; D000605:Amino Alcohols / Q000138:chemical synthesis*; D000818:Animals; D002384:Catalysis; D020650:Combinatorial Chemistry Techniques; D008049:Lipase / Q000737:chemistry*; D010179:Pancreas / Q000201:enzymology; D013552:Swine
D000605:Amino Alcohols; C089584:4-aminobutanol; D008049:Lipase; D020155:3-Hydroxybutyric Acid