GB789328A - Improvements in or relating to production of l-glutamine - Google Patents

Abstract

L-glutamine is prepared by contacting with a hydrogen halide under anhydrous conditions, a solution of the gamma-amide of N-carboallyloxy-L-glutamic acid or N-carboallyloxy-L-glutamic acid 2-substituted in the allyl group by an alkyl or phenyl group, or the ammonium salt thereof or a mixture of the gamma-amide and its ammonium salt. The gamma-amide may be used in formic acid, acetic acid, propionic acid, nitromethane or dioxane solution. The hydrogen halide, e.g. the chloride or bromide may also be used in solution. The reaction may be effected at about 15 DEG -40 DEG C. The product contains the glutamine in the form of its hydrogen halide and the product may be worked up by dissolving it in absolute methanol, adding aqueous ammonia to adjust the pH to about 5.5, adding acetone and then crystallizing out the L-glutamine. The crude glutamine may be purified by dissolving it in a minimum amount of hot water, adding acetone and crystallizing at about 0 DEG C. The gamma-amides used as starting materials may be prepared from a gamma ester of L-glutamic acid, e.g. an aliphatic or phenyl ester, by treating the gamma-ester with allyl or a 2-alkyl or 2-phenyl-allyl chloroformate, suitably in the presence of magnesium oxide or hydroxide at about 0-55 DEG C. and then treating the resulting N-carboallyloxy-L-glutamic acid ester, which may be isolated by a solvent-extraction method, with ammonia to form the required gamma-amide. Amidation may be carried out with liquid, aqueous or alcoholic ammonia in an autoclave at various temperatures from room temperature up to about 65 DEG C. In an example, L-glutamic acid is esterified with methanol, the resulting methyl ester is reacted in an aqueous medium containing Mg(OH)2 with allyl chloroformate, the product is amidated with aqueous ammonia and the resulting mixture of N-carboallyloxy-L-glutamine and its ammonium salt is stripped under reduced pressure and then reacted with hydrogen bromide in glacial acetic acid solution and the reaction mixture is worked up to isolate the L-glutamine in crystalline form. The gammaethyl, propyl, isopropyl and butyl ester of L-glutamic acid and methallyl chloroformate are other specified reagents. These gamma esters are prepared by esterification of the acid with the alcohol. Specifications 752,889 and 786,226 are referred to.