Chemical Synthesis And Biotransformation Of α-amimoalcohol

Chiral α-aminoalcohols and their derivatives have been proved to be a class of functionally active compounds with a wide applicability in medicinal chemistry. It is also widely used in asymmetric synthesis as chiral auxiliaries. There are a number of examples of important molecules which contain chiral aminoalcohols, including: alkaloids, antibiotics, and the HIV-RT inhibitors.Gaining control over the stereochemistry of chiral centers at both the alcohol and amine at reasonable cost is the key to the successful production of these important chemical intermediates. The reduction of the ketone catalyzed by an alcohol dehydrogenase occurs with a high degree of stereoselectivity, reducing only one of the two ketone enantiomers. Further, the reduction of the ketone is highly stereoselective for the production of a single alcohol stereoisomer. Thus, two chiral centers are generated simultaneously by this enzymatic reaction.Racemic substrates a-aminoketones, a-nitrile and nitryl substituted ketones were synthesized by chemical methods, α-oxoethyl ester was synthesized starting from benzoyl chloride. The substrates structures were determined by IR and ~1H-NMR.a-Aminoketones were subjected to biotransformation by Baker's yeast and Geotrichum candidum yielding optically active chiral a-aminoalcohols. The optimal biotransformation conditions (temperature, pH, cells concentration, substrate concentration and co-substrate concentration) were estimated by orthogonal experimental design.The products were analysed by HPLC using chiral stationary phases. 3-acetylamino-4-phenyl-2-butyl alcohol has been obtained with >98% diastereomeric excess and mandelic acid methyl ester with >99% enantiomeric excess。...