title: Aminotransferase catalysis applied to the synthesis of a PAF antagonist.
abstract: (R)-alpha-Methyl-3-pyridinebutanamine (5) was required as a key intermediate for production of the PAF antagonist [(R)-(E,E)-5-(4-methoxyphenyl)-N-1- methyl-4-(3-pyridinyl)butyl-2,4-decadienamide (1). A method meeting the requirements of technical simplicity and economic viability was developed using an aminotransferase ex. B. megaterium to catalyze a kinetic resolution of racemic alpha-methyl-3-pyridinebutanamine (3). 5-(3-Pyridinyl)-2-pentanone (4) produced from the (S)-enantiomer, with co-generation of alanine, is recycled by catalytic reductive amination.
authors.affiliation: Roche Research Center, Hoffmann-La Roche Inc., Nutley, NJ 07110.
authors.forename: D L
authors.initials: DL
authors.lastname: Coffen
authors.forename: M
authors.initials: M
authors.lastname: Okabe
authors.forename: R C
authors.initials: RC
authors.lastname: Sun
authors.forename: S
authors.initials: S
authors.lastname: Lee
authors.forename: G W
authors.initials: GW
authors.lastname: Matcham
mesh_terms: D001410:Bacillus megaterium / Q000201:enzymology; D002384:Catalysis; D007202:Indicators and Reagents; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*; D053284:Polyunsaturated Alkamides; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013237:Stereoisomerism; D000637:Transaminases / Q000302:isolation & purification / Q000378:metabolism*
chemical_list: D007202:Indicators and Reagents; D010972:Platelet Activating Factor; D053284:Polyunsaturated Alkamides; D011725:Pyridines; C073133:Ro 24-0238; D000637:Transaminases