Chemo-enzymatic synthesis of (R)-(-)-1-(2-naphthyl)-2-(N-methyl) aminoethanol using (R)-oxynitrilase

Using 2-naphthaldehyde as starting material, optical active (R)-(-)-1-(2-naphthyl)-2-(N-methyl) aminoethanol 5 was synthesized via transcyanation, reduction of -CN, formylation and formamide reduction. Oxynitrilases from nuts of almond, loquat, peach and apple were employed respectively to catalyze the reaction of addicting HCN onto the substrate to generate the corresponding (R)-cyanohydrins. Almond meal shows the best catalytic activity, and the yield and enantiomeric excess (ee) of the product are 68.8% and 88.3%, respectively. O-protected cyanohydrin 2 is further transformed into the title compound 5 with total yield of 47% and ee of 88.0% via chemical reactions involving three steps. The product structures of all reaction steps were confirmed by IR, and 1H-NMR. Experimental results indicate that the optical purity of the chiral cyanohydrin obtained by enzymatic reaction is quite high, and it is an excellent starting material for the stereoselective synthesis of the chiral amino alcohol compounds. Moreover, the optical purity can be well retained for the product of each latterly following chemical transformation step.