Réaction #531898

Équation de réaction

H-D-iGlu-D-Trp-OH

D-isoglutamyl-D-tryptophan

HCl

tert-butyl methyl ether

HCl

D-isoglutamyl-D-tryptophan

HCl

dichloromethane

→

thymodepressin

H-D-iGlu-D-Trp-OH

D-isoglutamyl-D-tryptophan

Conditions de réaction

Traitement

1. 1
   AutreH-D-Glu-(γ-D-Trp-OR2)-α-OR1 precipitates out of dichloromethane
2. 2
   Autrecan be removed by filtration
3. 3
   workup.ADDITIONTreatment of the acid addition salt with a metal hydroxide in an inert solvent such as methanol
4. 4
   Autrefor one phase homogeneous hydrolysis
5. 5
   Autreaffords
6. 6
   ExtractionUpon extraction of the reaction mixture with a water immiscible solvent such as ethyl acetate or tert-butyl methyl ether
7. 7
   Autrethe solution is evaporated
8. 8
   workup.ADDITIONthe base addition salt (in mono carboxylate form) of H-D-iGlu-D-Trp-OH

Mode opératoire

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.

Source