Isoglutamine or α-glutamine is a gamma amino acid derived from glutamic acid by substituting the carboxyl group in position 1 with an amide group. This is in contrast to the proteinogenic amino acid glutamine, which is the 5-amide of glutamic acid.

Isoglutamine can form the C-terminus of a peptide chain, as in muramyl dipeptide (MDP), a constituent of bacterial cell walls. It can also occur inside a peptide chain, in which case the chain is continued at the carboxyl group and isoglutamine behaves as a γ-amino acid, as in mifamurtide, a synthetic derivative of MDP used to treat osteosarcoma.

Synthesis of L- Isoglutamine

In the course of our studies on histidine metabolism it became necessary to prepare some L-isoglutamine.  Swan and duVigneaud have published the only uilambiguous syilthesis of L-isoglutamine. t consists in the preparation of N-p-toluenesulphonyl-L-glutamic acid, the conversion to N-tos-5-oxo-2-pyrrolidine-carboxyclh loride, the amidatioil to N-tos-5-oxo-2- pyrrolidine-carboxamide, the conversion to N-tos-L-isoglutamine, and the subsequent hydrogenation with sodium in liquid ammoilia to give L-isoglutamine.

We have found it more convenient to prepare L-isoglutamine by the amidation of N-CBZ-γ-benzyl-L-glutamate by the mixed anhydride procedure  of Boissoililas, followed by catalytic hydrogenolysis of the resultiilg amide. The method is evidently unambiguous and L-isoglutamine is the only product formed. This was verified by paper chromatography in four solvent systems.

Experimental

N-CBZ-γ-benzyl-L-isoglutamine (5 gm.) was dissolved in 100 ml. of 50% ethanol and hydrogenated for 12 hr. at room temperature and atmospheric pressure in the presence of palladium catalyst (5% Pd on calcium carbonate). The catalyst was filtered off and a trace of calcium ions was removed with oxalic acid. The solution was evaporated to dryness, the residue dissolved in a small amount of hot water, and the solution treated with charcoal. Alcohol was added to the cloud point and L-isoglutamine was recovered from the chilled solution as fine white crystals, m.p. 186-188°, yield 65%.