N-Acetyl-D-leucine

N-Acetyl-D-leucine Property

Melting point:

176-177C

Boiling point:

369.7±25.0 °C(Predicted)

Density 

1.069±0.06 g/cm3(Predicted)

refractive index 

23 ° (C=4, EtOH)

storage temp. 

Sealed in dry,Store in freezer, under -20°C

solubility 

DMSO (Slightly), Ethanol (Slightly, Sonicated), Methanol (Slightly)

form 

Solid

pka

3.67±0.10(Predicted)

color 

White to Off-White

InChI

InChI=1S/C8H15NO3/c1-5(2)4-7(8(11)12)9-6(3)10/h5,7H,4H2,1-3H3,(H,9,10)(H,11,12)/t7-/m1/s1

InChIKey

WXNXCEHXYPACJF-SSDOTTSWSA-N

SMILES

C(O)(=O)[C@@H](CC(C)C)NC(C)=O

CAS DataBase Reference

19764-30-8(CAS DataBase Reference)

Safety

Hazard Codes 

Xi

Risk Statements 

36/37/38

Safety Statements 

26-36

WGK Germany 

3

HS Code 

29241900

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Warning

Hazard statements

H302Harmful if swallowed

H315Causes skin irritation

H320Causes eye irritation

H335May cause respiratory irritation

Precautionary statements

P264Wash hands thoroughly after handling.

P264Wash skin thouroughly after handling.

P270Do not eat, drink or smoke when using this product.

P301+P312IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.

P330Rinse mouth.

N-Acetyl-D-leucine Chemical Properties,Usage,Production

Chemical Properties

White to off-white powder

Uses

N-Acetyl-D-leucine may be used with other D-aminoacylated amino acids as a substrate for the identification, differentiation and characterization of D-aminoacylase(s)/amidohydrolase(s).

Definition

ChEBI: N-acetyl-D-leucine is the N-acetyl derivative of D-leucine. It is a N-acetyl-D-amino acid and a D-leucine derivative. It is a conjugate acid of a N-acetyl-D-leucinate. It is an enantiomer of a N-acetyl-L-leucine.

Biological Activity

N-Acetyl-D-leucine is a substrate for D-aminoacylase from Alcaligenes xylosoxydans subsp. xylosoxydans A-6. N-Acetyl-D-leucine is used to help differentiate members of the amidohydrolase enzyme superfamily. It is a preferred substrate of Gox1177 from Gluconobacter oxidans.

Synthesis

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

[1] Patent: WO2006/93719, 2006, A1. Location in patent: Page/Page column 34; 35
[2] Organic Process Research and Development, 2005, vol. 9, # 5, p. 640 - 645