title: Enzymatic synthesis of L-6-hydroxynorleucine.
abstract: L-6-Hydroxynorleucine, a key chiral intermediate used for synthesis of a vasopeptidase inhibitor, was prepared in 89% yield and > 99% optical purity by reductive amination of 2-keto-6-hydroxyhexanoic acid using glutamate dehydrogenase from beef liver. In an alternate process, racemic 6-hydroxynorleucine produced by hydrolysis of 5-(4-hydroxybutyl)hydantoin was treated with D-amino acid oxidase to prepare a mixture containing 2-keto-6-hydroxyhexanoic acid and L-6-hydroxynorleucine followed by the reductive amination procedure to convert the mixture entirely to L-6-hydroxynorleucine, with yields of 91 to 97% and optical purities of > 99%.
authors.affiliation: Department of Microbial Technology, Bristol-Myers Squibb, New Brunswick, NJ 08903, USA.
authors.forename: R L
authors.initials: RL
authors.lastname: Hanson
authors.forename: M D
authors.initials: MD
authors.lastname: Schwinden
authors.forename: A
authors.initials: A
authors.lastname: Banerjee
authors.forename: D B
authors.initials: DB
authors.lastname: Brzozowski
authors.forename: B C
authors.initials: BC
authors.lastname: Chen
authors.forename: B P
authors.initials: BP
authors.lastname: Patel
authors.forename: C G
authors.initials: CG
authors.lastname: McNamee
authors.forename: G A
authors.initials: GA
authors.lastname: Kodersha
authors.forename: D R
authors.initials: DR
authors.lastname: Kronenthal
authors.forename: R N
authors.initials: RN
authors.lastname: Patel
authors.forename: L J
authors.initials: LJ
authors.lastname: Szarka
mesh_terms: D000818:Animals; D002374:Catalase / Q000737:chemistry / Q000378:metabolism; D002417:Cattle; D003605:D-Amino-Acid Oxidase / Q000737:chemistry / Q000378:metabolism; D042843:Glucose 1-Dehydrogenase; D005948:Glucose Dehydrogenases / Q000737:chemistry / Q000378:metabolism; D005969:Glutamate Dehydrogenase / Q000737:chemistry / Q000378:metabolism; D007668:Kidney / Q000201:enzymology; D008099:Liver / Q000201:enzymology; D003904:Mitosporic Fungi / Q000201:enzymology; D009243:NAD / Q000378:metabolism; D009646:Norleucine / Q000031:analogs & derivatives* / Q000138:chemical synthesis
chemical_list: D009243:NAD; C001409:epsilon-hydroxynorleucine; D009646:Norleucine; D005948:Glucose Dehydrogenases; D042843:Glucose 1-Dehydrogenase; D002374:Catalase; D005969:Glutamate Dehydrogenase; D003605:D-Amino-Acid Oxidase