Hydrochloric Acid → Thymodepressin

Participants

Reaction Steps

A solution of the base addition salt of D-isoglutamyl-D-tryptophan is prepared by the acid deprotection of the dipeptide Boc-D-Glu-(γ-D-Trp-OR2)-α-OR1, wherein each of R1 and R2 is independently selected from the group consisting of benzyl and C1-C4 alkyl. For example, HCl deprotection of Boc-D-Glu-(γ-D-Trp-OR2)-α-OR1 in an inert solvent such as dichloromethane, affords the HCl salt of H-D-Glu-(γ-D-Trp-OR2)-α-OR1. For the combination where R1 is benzyl and R2 is methyl, the product HCl.H-D-Glu-(γ-D-Trp-OR2)-α-OR1 precipitates out of dichloromethane and can be removed by filtration. Treatment of the acid addition salt with a metal hydroxide in an inert solvent such as methanol for one phase homogeneous hydrolysis or with tert-butyl methyl ether for two phase hydrolysis affords H-D-iGlu-D-Trp-OH base addition salt in solution. Upon extraction of the reaction mixture with a water immiscible solvent such as ethyl acetate or tert-butyl methyl ether, the aqueous phase is neutralized to pH of about 6 to about 7 and the solution is evaporated to reduced the volume to an estimated ratio of less than about 1 part solute:8 parts water. The solute, as predicted by the speciation calculations as shown in FIG. 8, is the base addition salt (in mono carboxylate form) of H-D-iGlu-D-Trp-OH. If sodium hydroxide is used as the metal hydroxide, the solute will be the mono sodium form of the H-D-iGlu-D-Trp-OH in water. Adjustment of this solution to pH of about 2.5 to about 3.0 will result in the precipitation of solid thymodepressin, H-D-iGlu-D-Trp-OH.

Provenance & Evidence