GB752889A - Improvements in or relating to glutamic acid derivatives and process of producing the same - Google Patents

Abstract

The invention comprises substituted N-carboallyloxy-L-glutamic acids having the formula <FORM:0752889/IV(a)/1> wherein X represents an alkoxy group or the group -NH2 and R1 is hydrogen, alkyl or phenyl, which are prepared by reacting a gamma-alkyl ester of the natural optically active isomer of glutamic acid with a chloroformate Cl.COOCH2-CR1=CH2, where R1 is as defined above, so producing the gamma-alkyl ester of an N-carboallyloxy-L-glutamic acid and this compound may be amidated with ammonia to yield the gamma-amide of the carboallyloxy-glutamic acid. The amide may be reduced to L-glutamine. The amidation is preferably carried out at between about 0 DEG C. and 60 DEG C. for about 20 to 24 hours, using aqueous or alcoholic ammonia or liquid ammonia. The reduction of the amide to L-glutamine may be effected by conventional reducing agents, e.g. hydrogen in the presence of a catalyst such as platinum or palladium but preferably liquid ammonia and sodium are used. In an example, L-glutamic acid is esterified with anhydrous methanol using sulphuric acid as catalyst and the resulting gamma-methyl ester is isolated and reacted with allyl chloroformate using magnesium hydroxide as catalyst. The methyl N-carboallyloxy glutamic acid ester obtained is isolated and reacted with aqueous ammonia in a pressure bottle; the resulting gamma-amide is then dissolved in liquid ammonia and reduced to L-glutamine with sodium. Other specified reagents are the gamma-ethyl, isopropyl and butyl esters of L-glutamic acid and methallyl and phenallyl chloroformates.