Microbial deracemization of alpha-substituted carboxylic acids: substrate specificity and mechanistic investigation.
A new enzymatic method for the preparation of optically active alpha-substituted carboxylic acids is reported. This technique is called deracemization reaction, which provides us with a route to obtain the enantiomerically pure compounds, theoretically in 100% yield starting from the racemic mixture. This means that the synthesis of a racemate is almost equal to the synthesis of the optically active compound, and this concept is entirely different from the commonly accepted one in the asymmetric synthesis. Using the growing cell system of Nocardia diaphanozonaria JCM3208, racemates of 2-aryl- and 2-aryloxypropanoic acid are deracemized smoothly and (R)-form-enriched products are recovered in high chemical yield (>50%). In addition, using optically active starting compounds and deuterated derivatives as well as inhibitors, we have disclosed the fact that a new type of enzyme takes part in this biotransformation, and that the reaction proceeds probably via the same mechanism as that in rat liver.
Kato
Dai-ichiro
D
Department of Biosciences and Informatics, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama 223-8522, Japan.
Mitsuda
Satoshi
S
Ohta
Hiromichi
H
D001711:Biotransformation; D002264:Carboxylic Acids / Q000138:chemical synthesis / Q000302:isolation & purification* / Q000378:metabolism*; D003066:Coenzyme A Ligases; D041961:Deuterium Exchange Measurement; D009615:Nocardia / Q000201:enzymology / Q000378:metabolism*; D013237:Stereoisomerism; D013379:Substrate Specificity
D002264:Carboxylic Acids; D003066:Coenzyme A Ligases