title: Enantioselective synthesis of a GPR40 agonist AMG 837 via catalytic asymmetric conjugate addition of terminal alkyne to α,β-unsaturated thioamide.
abstract: A concise enantioselective synthetic route to a potent GPR40 agonist AMG 837 is described. The crucial catalytic asymmetric conjugate addition of terminal alkyne was promoted by a soft Lewis acid/hard Brønsted base cooperative catalyst, allowing efficient construction of the requisite stereogenic center. The thioamide functional group is key to both activation in asymmetric alkynylation and facile transformation into carboxylic acid.
authors.affiliation: Institute of Microbial Chemistry, Tokyo, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Yazaki
authors.forename: Naoya
authors.initials: N
authors.lastname: Kumagai
authors.forename: Masakatsu
authors.initials: M
authors.lastname: Shibasaki
mesh_terms: D000480:Alkynes / Q000737:chemistry*; D001713:Biphenyl Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002384:Catalysis; D020650:Combinatorial Chemistry Techniques; D006801:Humans; D015394:Molecular Structure; D043562:Receptors, G-Protein-Coupled / Q000819:agonists*; D013237:Stereoisomerism; D013854:Thioamides / Q000737:chemistry*; D010666:Phenylpropionates
chemical_list: D000480:Alkynes; D001713:Biphenyl Compounds; D043562:Receptors, G-Protein-Coupled; D013854:Thioamides; C473034:FFAR1 protein, human; C557933:AMG-837; D010666:Phenylpropionates