The chemoenzymatic preparation of a nine-member Ugi condensation library is
described. The carboxylic acid and amine precursors are based on 3-hydroxy
butyrate and 4-amino-1-butanol, respectively, and have been acylated select
ively using a variety of acyl donors catalyzed by porcine pancreatic lipase
. The enzyme is selective for the hydroxyl functionalities on both precurso
rs, thereby yielding 8-acyl-butyric acid and 4-amino-1-acyl compounds. Thes
e enzymatically generated derivatives were then subjected to a four-compone
nt Ugi condensation reaction in the presence of acetaldehyde and methyl iso
cyanoacetate. isolated yields of the alpha-(acylamino)amide Ugi products ra
nged from 72-95%. The inherent chemoselectivity of enzymatic catalysis may
play an increasingly important role in expanding the structural diversity t
hat can be achieved by chemical multicomponent condensation reactions. (C)
2000 John Wiley & Sons, Inc.