ChemicalBook CAS DataBase List L-Citrulline

L-Citrulline synthesis

6synthesis methods

Product Name:L-Citrulline
CAS Number:372-75-8
Molecular formula:C6H13N3O3
Molecular Weight:175.19

74-79-3 Synthesis

74-79-3
1066 suppliers
$5.00/25g

372-75-8
737 suppliers
$6.00/10g

Yield:372-75-8 91%

Reaction Conditions:

for 46 - 120 h;Product distribution / selectivity;Enzymatic reaction;

Steps:

EXAMPLES The following Examples have been included to illustrate modes of the presently disclosed subject matter. In light of the present disclosure and the general level of skill in the art, those of skill will appreciate that the following Examples are intended to be exemplary only and that numerous changes, modifications, and alterations can be employed without departing from the scope of the presently disclosed subject matter.Trial manufacturing and pilot production of Citrulline API have been performed. Two trial batches have produced in 15 L fermentors that were followed by two pilot scale batches. The trial batches and pilot productions are explained in more detail below. The purification of the crude material process includes endotoxin reduction and crystallization steps.Two batches of IOL each as well as a scaled-up consignment have been produced following the process of fermentation, extraction and refinement. The first batch began with 1 kg of arginine and resulted in the harvest of 9 L of liquor. The liquor was ultra-refined with 5 K membrane to remove endotoxin and yield 504 g of L-Citruline product. The net weight of L-Citrulline recovered from the stock solution is 685 g.The second batch began with 1 kg of arginine and resulted in the harvest of 9 L of liquor. After extraction and endotoxin removal with 10 K ultra-filter, 160 g of good quality L-Citrulline product was obtained. L-Citrulline recovered from the stock solution weighs 963g.A minor alteration in processing conditions was introduced after the first batch. Initially, the fermentation broth was filtered and the resulting mycel was used to convert arginine, hence the color of the intermediate product from the first batch appeared paler. A second crystallization process was implemented before obtaining the final product. However, in the second batch, the fermentation broth was used to convert arginine directly. The color of broth was therefore brought into the inversion liquor. This resulted in a solution of darker appearance. At the extraction stage, the number of recrystallization operations was increased. The expected yield was not high due to the high quantity of Citrulline present in the stock solution. Reduction of the concentration of Citrulline in the stock solution should result in improved yield. A scale-up batch was executed with 75 kg arginine. The processing of inversion liquor was extended over three episodes. The crude material yielded can be processed by endotoxin reduction, filtration, drying, and inspection before the final purified product can be collected.The validation of trial batches and the scaled-up pilot batches were commenced in the pilot plant facilities. Validation was performed in two batches using 15 L fermentation. This was followed by the pilot scale production. Results are outlined below in Table I.

References:

WO2009/25829,2009,A1 Location in patent:Page/Page column 14-15

3184-13-2 Synthesis