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Chemoenzymatic construction of a four‐component Ugi combinatorial library
Author(s) -
Liu XiaoChuan,
Clark Douglas S.,
Dordick Jonathan S.
Publication year - 2000
Publication title -
biotechnology and bioengineering
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.136
H-Index - 189
eISSN - 1097-0290
pISSN - 0006-3592
DOI - 10.1002/1097-0290(20000820)69:4<457::aid-bit12>3.0.co;2-l
Subject(s) - chemoselectivity , chemistry , ugi reaction , amide , lipase , acetaldehyde , catalysis , organic chemistry , amine gas treating , condensation reaction , enzyme , combinatorial chemistry , ethanol , isocyanide
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 α‐(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. © 2000 John Wiley & Sons, Inc. Biotechnol Bioeng 69: 457–460, 2000.