Enzymatic synthesis of L-6-hydroxynorleucine.
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%.
Hanson
R L
RL
Department of Microbial Technology, Bristol-Myers Squibb, New Brunswick, NJ 08903, USA.
Schwinden
M D
MD
Banerjee
A
A
Brzozowski
D B
DB
Chen
B C
BC
Patel
B P
BP
McNamee
C G
CG
Kodersha
G A
GA
Kronenthal
D R
DR
Patel
R N
RN
Szarka
L J
LJ
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
D009243:NAD; C001409:epsilon-hydroxynorleucine; D009646:Norleucine; D005948:Glucose Dehydrogenases; D042843:Glucose 1-Dehydrogenase; D002374:Catalase; D005969:Glutamate Dehydrogenase; D003605:D-Amino-Acid Oxidase