N-Acetyl-D-leucine

Chemical Properties

Uses

Definition

Biological Activity

Synthesis

328-38-1

108-24-7

19764-30-8

Procedure: the preparation of compound 10 (N-acetyl-D-leucine) was carried out by an improved prior art method (see Am. Chem. Soc., 1951, 73, 3359-3360) as follows: In a 22-liter four-neck flask equipped with a thermocouple controller, an overhead mechanical stirrer, and two 2.0-liter dosing funnels. Deionized water (2.45 L) and D-leucine (99% e.e., 917.0 g, 7.0 mol) were added to the flask and stirring was initiated. Acetic anhydride (99%, 2142.0 g, 21.0 mol) and 20% aqueous NaOH solution (2.45 L, 49.0 mol) were added simultaneously and slowly dropwise over a period of 3 to 4 h. The temperature of the reaction was maintained between 5 and 15°C. The reaction temperature was controlled by adjusting the titration rate of the basic solution and acetic anhydride as well as wet ice cooling. The pH of the reaction mixture was maintained in the slightly basic range (pH 8-9) during the reaction using pH test paper every 10-15 min. The reaction process was monitored by HPLC and LC-MS. After completion of addition, stirring of the reaction mixture was continued for 1 h. Subsequently, acidification was carried out by slow addition of 37% HCl solution (4.76 L, 49.0 mol) over a period of 30 min. After acidification, a white solid precipitated and the slurry was stirred at 5°C to 15°C for 2 hours. The solid product was separated by filtration, washed with deionized water (2.0 L x 7), dried by air suction for 3 h, and finally dried in a vacuum oven at 60°C for 16 h (until the weight of the solid no longer decreased). Finally 1083 g (89% yield) of N-acetyl-D-leucine (compound 10) was obtained as a white powdery solid with high optical purity (>97% e.e.). The structure of the product was confirmed by 1H-NMR and LC-MS analyses and it could be used in subsequent steps without further purification.

in vivo

References