title: Asymmetric hydrogenation of N-sulfonylated-alpha-dehydroamino acids: toward the synthesis of an anthrax lethal factor inhibitor.
abstract: A novel and highly enantioselective Ru-catalyzed hydrogenation of N-sulfonylated-alpha-dehydroamino acids has been discovered and demonstrated in the synthesis of an anthrax lethal factor inhibitor (LFI). Herein, this methodology is used to prepare N-sulfonylated amino acids in up to 98% ee. This unprecedented hydrogenation uses a chiral Ru catalyst rather than Rh as typical for acylated dehydroamino acids and esters, and this work reports the first asymmetric hydrogenation of a tetrasubstituted dehydroamino acid derivative using a Ru catalyst. [reaction: see text]
authors.affiliation: Department of Process Research and the Catalytic Reactions Discovery and Development Lab, Merck and Co Inc., P.O. Box 2000, Rahway, New Jersey 07065. scott_shultz@merck.com
authors.forename: C Scott
authors.initials: CS
authors.lastname: Shultz
authors.forename: Spencer D
authors.initials: SD
authors.lastname: Dreher
authors.forename: Norihiro
authors.initials: N
authors.lastname: Ikemoto
authors.forename: J Michael
authors.initials: JM
authors.lastname: Williams
authors.forename: Edward J J
authors.initials: EJ
authors.lastname: Grabowski
authors.forename: Shane W
authors.initials: SW
authors.lastname: Krska
authors.forename: Yongkui
authors.initials: Y
authors.lastname: Sun
authors.forename: Peter G
authors.initials: PG
authors.lastname: Dormer
authors.forename: Lisa
authors.initials: L
authors.lastname: Dimichele
mesh_terms: D000596:Amino Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000942:Antigens, Bacterial; D001408:Bacillus anthracis / Q000737:chemistry / Q000472:pathogenicity; D001427:Bacterial Toxins / Q000037:antagonists & inhibitors*; D002384:Catalysis; D006865:Hydrogenation; D012428:Ruthenium / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: D000596:Amino Acids; D000942:Antigens, Bacterial; D001427:Bacterial Toxins; C030325:anthrax toxin; D012428:Ruthenium