title: The Synthesis of α,α-Disubstituted α-Amino Acids via Ichikawa Rearrangement.
abstract: An approach to α,α-disubstituted α-amino acids is reported. The key step is allyl cyanate-to-isocyanate rearrangement. As demonstrated, the resultant allyl isocyanates can be directly trapped with various nucleophiles, for instance, alcohols, amines, and organometallic reagents, to provide a broad range of N-functionalized allylamines. The developed method has been successfully applied in the synthesis of two bioactive peptides: 2-aminoadamantane-2-carboxylic acid derived P2X7-evoked glutamate release inhibitor and 4-amino-tetrahydropyranyl-4-carboxylic acid derived dipeptide GSK-2793660, which is currently in clinical trials as cathepsin C inhibitor for the treatment of cystic fibrosis, noncystic fibrosis bronchiectasis, ANCA-associated vasculitis and bronchiectasis.
authors.affiliation: Institute of Organic Chemistry , Polish Academy of Sciences, Kasprzaka 44/52, 01-224 Warsaw, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Szcześniak
authors.affiliation: Institute of Organic Chemistry , Polish Academy of Sciences, Kasprzaka 44/52, 01-224 Warsaw, Poland.
authors.forename: Michał
authors.initials: M
authors.lastname: Pieczykolan
authors.affiliation: Institute of Organic Chemistry , Polish Academy of Sciences, Kasprzaka 44/52, 01-224 Warsaw, Poland.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Stecko
mesh_terms: D000498:Allyl Compounds / Q000737:chemistry*; D000547:Amantadine / Q000031:analogs & derivatives* / Q000737:chemistry; D000596:Amino Acids / Q000737:chemistry*; D001669:Biochemical Phenomena; D003485:Cyanates / Q000737:chemistry*; D004151:Dipeptides / Q000138:chemical synthesis* / Q000737:chemistry; D007202:Indicators and Reagents / Q000737:chemistry; D017953:Isocyanates / Q000737:chemistry*; D015394:Molecular Structure; D011714:Pyrans / Q000737:chemistry; D013237:Stereoisomerism
chemical_list: C000608640:4-amino-tetrahydropyranyl-4-carboxylic acid; D000498:Allyl Compounds; D000596:Amino Acids; D003485:Cyanates; D004151:Dipeptides; D007202:Indicators and Reagents; D017953:Isocyanates; D011714:Pyrans; C491149:allyl isocyanate; C005660:adamantanine; D000547:Amantadine; C000608638:GSK-2793660