title: Chiral proton catalysis of secondary nitroalkane additions to azomethine: synthesis of a potent GlyT1 inhibitor.
abstract: The first enantioselective synthesis of a potent GlyT1 inhibitor is described. A 3-nitroazetidine donor is used in an enantioselective aza-Henry reaction catalyzed by a bis(amidine)-triflic acid salt organocatalyst, delivering the key intermediate with 92% ee. This adduct is reductively denitrated and converted to the target through a short sequence, thereby allowing assignment of the absolute configuration of the more potent enantiomer.
authors.affiliation: Department of Chemistry & Vanderbilt Institute of Chemical Biology Vanderbilt University, Nashville, TN 37235-1822, USA.
authors.forename: Tyler A
authors.initials: TA
authors.lastname: Davis
authors.forename: Michael W
authors.initials: MW
authors.lastname: Danneman
authors.forename: Jeffrey N
authors.initials: JN
authors.lastname: Johnston
mesh_terms: D000473:Alkanes / Q000138:chemical synthesis / Q000737:chemistry*; D001391:Azo Compounds / Q000138:chemical synthesis / Q000737:chemistry*; D002384:Catalysis; D050487:Glycine Plasma Membrane Transport Proteins / Q000037:antagonists & inhibitors*; D006801:Humans; D009574:Nitro Compounds / Q000138:chemical synthesis / Q000737:chemistry*; D011522:Protons; D013237:Stereoisomerism; D013882:Thiosemicarbazones / Q000138:chemical synthesis / Q000737:chemistry*
chemical_list: D000473:Alkanes; D001391:Azo Compounds; D050487:Glycine Plasma Membrane Transport Proteins; D009574:Nitro Compounds; D011522:Protons; C493268:SLC6A9 protein, human; D013882:Thiosemicarbazones; C512188:azomethine