The design and synthesis of 2,5-linked pyrrolinones. A potential non-peptide peptidomimetic scaffold.
The de novo design and initial synthetic studies directed toward construction of a novel non-peptide scaffold for beta-strand/sheet and related secondary peptide structural mimics are described. The scaffold, consisting of a repeating array of 2,5,5-trisubstituted pyrrolinone (enaminone) units punctuated with appropriate amino acid side chains, is conceptually related to our previously successful 3,5-linked polypyrrolinone non-peptide peptidomimetic scaffold. Construction of the 2,5,5-trisubstituted pyrrolinone ring system proceeds via intramolecular condensation of an N-protected amino dione. The latter is prepared from a protected alpha-amino ketone and aldehyde via an aldol-oxidation reaction sequence.
Smith
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AB
Department of Chemistry, University of Pennsylvania, Philadelphia 19104, USA.
Knight
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SD
Sprengeler
P A
PA
Hirschmann
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R
D018360:Crystallography, X-Ray; D017320:HIV Protease Inhibitors / Q000138:chemical synthesis*; D008958:Models, Molecular; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D011758:Pyrroles / Q000737:chemistry*
D017320:HIV Protease Inhibitors; D011758:Pyrroles