title: Stereochemical assignment of the protein-protein interaction inhibitor JBIR-22 by total synthesis.
abstract: Recent reports have highlighted the biological activity associated with a subfamily of the tetramic acid class of natural products. Despite the fact that members of this subfamily act as protein-protein interaction inhibitors that are of relevance to proteasome assembly, no synthetic work has been reported. This may be due to the fact that this subfamily contains an unnatural 4,4-disubstitued glutamic acid, the synthesis of which provides a key challenge. A highly stereoselective route to a masked form of this unnatural amino acid now enabled the synthesis of two of the possible diastereomers of JBIR-22 and allowed the assignment of its relative and absolute stereochemistry.
authors: School of Chemistry and Biomedical Sciences Research Complex, University of St Andrews and EaStCHEM, North Haugh, St Andrews, Fife (UK).
authors: Alan R
authors: AR
authors: Healy
authors: Miho
authors: M
authors: Izumikawa
authors: Alexandra M Z
authors: AM
authors: Slawin
authors: Kazuo
authors: K
authors: Shin-Ya
authors: Nicholas J
authors: NJ
authors: Westwood
mesh_terms: D000596:Amino Acids / Q000737:chemistry; D001688:Biological Products / Q000737:chemistry; D005971:Glutamates / Q000138:chemical synthesis / Q000737:chemistry; D008968:Molecular Conformation; D046988:Proteasome Endopeptidase Complex / Q000187:drug effects; D054730:Protein Interaction Domains and Motifs / Q000187:drug effects*; D011760:Pyrrolidinones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013237:Stereoisomerism; D013764:Tetrahydronaphthalenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000596:Amino Acids; D001688:Biological Products; D005971:Glutamates; C549607:JBIR-22; D011760:Pyrrolidinones; D013764:Tetrahydronaphthalenes; D046988:Proteasome Endopeptidase Complex
keywords: natural products; stereochemistry; tetramic acids; total synthesis; unnatural amino acids
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