Isoglutamine

The structure of the native immunostimulatory MDPs was found to be IV-acetyl muramyl-L-alanyl-D-isoglutamine. (/V-Acetyl muramic acid is a base component of bacterial peptidoglycan.) Native TDM is a potent pyrogen and is too toxic for general use as an adjuvant. The molecular basis underlining MDP s adjuvanticity remains to be fully elucidated. Administration of MDP, however, is known to activate a number of cell types that play direct/indirect roles in immune function, and induces the secretion of various immunomodulatory cytokines (Table 13.14). 

FIGURE 8.2 Synthesis of isoglutamine by reaction of the mixed anhydride of protected glutamic acid with gaseous ammonia followed by deprotection by hydrogenolysis.11 a = EtOCOCl/Bu3N in dioxane b = anhydrous NH3 c = H2/Pd(CaC03). 

M Kraml, LP Bouthillier. Synthesis of L-isoglutamine from y-benzyl glutamate. Can... 

Figure 6.51 Fluoroalkyl derivatives of AFacetylmuramyl-L-alanyl-D-isoglutamine.

L-Glutamine [56-85-9] M 146.2, m 184-185", [alp +31.8" (M HCl). Likely impurities are glutamic acid, ammonium pyroglutamate, tyrosine, asparagine, isoglutamine, arginine. Crystd from water. 

The result suggested that the activation of the carboxyl group of glutamine derivatives increases the acidity of the C - H bond of the adjacent asymmetric carbon and thereby enhances the tendency to racemize. They thus came up with a new idea to use isoglutamine (35) instead of glutamine (11) as a starter. In this case, the carboxyl group to be activated for ring closure is removed from the vicinity of the asymmetric carbon atom (Fig. 4). 

The preparations of optical isomers of thalidomide (1) were examined by a route based on d- and L-isoglutamine (35). The thalidomide isomers were obtained in high yields by treating the optical isomers of N-phthalo-ylisoglutamine (36) at 0°C with thionyl chloride in DMF for 30 min. CDI... 

Scheme 19 Synthesis of (S)-thalidomide (1) from N-phthaloyl-L-isoglutamine [86,87]...

It has been suggested that in some way, thahdomide interferes with the action of certain of the B vitamins, that as a result of this antagonism fetal damage can occur, and that in the adult there may be a hnk between this effect and the polyneuropathy that thalidomide can cause (193). Thalidomide and its two isoglutamine derivatives caused... 

Barton, D H R, Augy-Dorey, S, Camara, J, DaUco, P, Delaumeny, J M, Gero, S D, Quiclet-Sire, B, Stutz, P, Synthetic methods for the preparation of basic D-pseudo-sugars and L-pseudo-sugars — synthesis of carbocyclic analogs of A-acetyl-muramyl-L-alanyl-D-isoglutamine (Mdp), Tetrahedron, 46, 215-230, 1990. 

Likely impurities are glutamic acid, ammonium pyroglutamate, tyrosine, asparagine, isoglutamine, arginine. Crystd from water. 

J. Farkas, M. Ledvina, J. Brokes, J. Jezek J. Zajicek and M. Zaoral, The synthesis of 0-(2-acetamido-2-deoxy-/3-D-glucopyranosyl)-(l— 4)-N-acetylnormuramoyl-L-a-aminobutanoyl-D-isoglutamine, Carbohydr. Res., 1987,163, 63-72. 

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