Aminotransferase catalysis applied to the synthesis of a PAF antagonist.
(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.
Coffen
D L
DL
Roche Research Center, Hoffmann-La Roche Inc., Nutley, NJ 07110.
Okabe
M
M
Sun
R C
RC
Lee
S
S
Matcham
G W
GW
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*
D007202:Indicators and Reagents; D010972:Platelet Activating Factor; D053284:Polyunsaturated Alkamides; D011725:Pyridines; C073133:Ro 24-0238; D000637:Transaminases