Premium
Synthesis of highly substituted 5‐(trifluoromethyl)ketoimidazoles using a mixed‐solid/solution phase motif
Author(s) -
Hamper Bruce C.,
Jerome Kevin D.,
Yalamanchili Gopi,
Walker Daniel M.,
Chott Robert C.,
Mischke Deborah A.
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/(sici)1097-0290(200024)71:1<28::aid-bit5>3.0.co;2-f
Subject(s) - trifluoroacetic anhydride , benzamidine , chemistry , solid phase synthesis , acylation , trifluoromethyl , trifluoroacetic acid , cleavage (geology) , organic chemistry , combinatorial chemistry , medicinal chemistry , stereochemistry , materials science , peptide , biochemistry , alkyl , fracture (geology) , composite material , enzyme , catalysis
Using a combination of solid phase synthesis for the preparation of N ‐substituted‐ N ‐acylglycines 7 followed by solution‐phase ring transformation of trifluoromethylacyl munchnone intermediate 8 , a library of 200 trisubstituted‐5‐trifluoromethylketo (TFMK) imidazoles 9 was prepared. In a sublibrary, bromoacetate resin 4 was treated with 5 amines in parallel to give N ‐substituted glycines 5 followed by acylation with 12 acid chlorides to provide, upon cleavage from the resin, 60 individual N‐substituted‐N‐acylglycines 7 . The glycines 7 were converted to munchnones 8 by treatment with trifluoroacetic anhydride followed by reaction with benzamidine to give trisubstituted‐5‐TFMK‐imidazoles 9 . The structural content of the library was analyzed using PlateView of the LCMS results, and individual members were isolated by automated preparative LCMS. © 2000 John Wiley & Sons, Inc. Biotechnol Bioeng (Comb Chem) 71:28–37, 2000.