3343-29-1

Usage

Uses

Used in Organic Chemistry:
N-Alpha-Phthalyl-L-Glutamine is used as a protective reagent for the amino group in peptide synthesis, ensuring the stability and selectivity of the amino acid during the synthesis process.
Used in Drug Development:
N-Alpha-Phthalyl-L-Glutamine is used as a valuable tool in the development of new drugs, facilitating the efficient and precise manipulation of peptide sequences, which is crucial for the creation of effective pharmaceutical compounds.
Used in Neurodegenerative Disease Treatment:
N-Alpha-Phthalyl-L-Glutamine is studied for its potential use in the treatment of neurodegenerative diseases, where its protective properties may contribute to the mitigation of disease progression.
Used in Targeted Drug Delivery:
N-Alpha-Phthalyl-L-Glutamine is considered as a prodrug for targeted drug delivery, where its properties can be leveraged to enhance the delivery of therapeutic agents to specific sites within the body, improving the efficacy and reducing the side effects of treatments.

InChI:InChI=1/C13H12N2O5/c14-10(16)6-5-9(13(19)20)15-11(17)7-3-1-2-4-8(7)12(15)18/h1-4,9H,5-6H2,(H2,14,16)(H,19,20)/t9-/m0/s1

Upstream product

• 25830-77-7 N-phthaloyl-L-glutamic anhydride 
• 841-67-8 (S)-thalidomide 
• 85-44-9 phthalic anhydride 
• 56-85-9 L-glutamine 
• 22509-74-6 N-ethoxycarbonylphthalimide 

Downstream Products

• 50-35-1 thalidomide 
• 73-22-3 L-Tryptophan 

Relevant academic research and scientific papers

CRYSTALLINE FORMS OF THALIDOMIDE AND PROCESSES FOR THEIR PREPARATION

The present invention relates to crystalline forms of thalidomide having a high polymorphic purity and to processes for their preparation. The present invention also relates to pharmaceutical preparations comprising the crystalline forms for the treatment of patients suffering from autoimmune, inflammatory or angiogenic disorders.

PROCESSES FOR THE PREPARATION OF THALIDOMIDE

The present invention provides a process for the preparation of thalidomide (I) comprising: i) reacting a compound of formula (II), where one of R represents -OH or -NH2 and the other of R represents -NH2 or -OH, respectively, with a phthaloylating agent in the presence of a base and a a non-polar organic solvent to obtain a phthaloyl derivative where R have the same meanings as above; and ii) dehydrating the phthaloyl derivative using a dehydrating agent selected from an acid anhydride, an acid halide, an ion exchange resin or a molecular sleve to obtain thalidomide (I).

AN IMPROVED PROCESS FOR THE PREPARATION OF THALIDOMIDE

An improved process for the preparation of Thalidomide a TNF-alpha inhibitor by the conversion of N-phthaloyl L-glutamine in presence of an active ingredient of inorganic acid salts such as 1,1-Carbonyldi(1,2,4-triazole) as a condensing agent.

A concise two-step synthesis of thalidomide

A two-step synthesis of thalidomide is presented. The sequence requires no purifications. Treatment of L-glutamine with N-carbethoxyphthalimide produces N-phthaloyl-L-glutamine. Cyclization of N-phthaloyl-L-glutamine to afford thalidomide is accomplished by treatment with CDI in the presence of a catalytic amount of DMAP.

Chiral inversion and hydrolysis of thalidomide: Mechanisms and catalysis by bases and serum albumin, and chiral stability of teratogenic metabolites

The chiral inversion and hydrolysis of thalidomide and the catalysis by bases and human serum albumin were investigated by using a stereoselective HPLC assay. Chiral inversion was catalyzed by albumin, hydroxyl ions, phosphate, and amino acids. Basic amino acids (Arg and Lys) had a superior potency in cataLyzing chiral inversion compared to acid and neutral ones. The chiral inversion of thalidomide is thus subject to Specific and general base catalysis, and it is suggested that the ability of HSA to catalyze the reaction is due to the basic groups of the amino acids Arg and Lys and not to a single catalytic site on the macromolecule. The hydrolysis of thalidomide was also base-catalyzed. However, albumin had no effect on hydrolysis, and there was no difference between the catalytic potencies of acidic, neutral, and basic amino acids. This may be explained by different reaction mechanisms of the chiral inversion and hydrolysis of thalidomide. Chiral inversion is deduced to occur by electrophilic substitution involving specific and general base catalysis, whereas hydrolysis is thought to occur by nucleophilic substitution involving specific and general base as well as nucleophilic catalysis. As nucleophilic attack is sensitive to steric properties of the catalyst, steric hindrance might be the reason albumin is not able to catalyze hydrolysis. 1H NMR experiments revealed that the three teratogenic metabolites of thalidomide, in sharp contrast to the drug itself, had complete chiral stability. This leads to the speculation that, were some enantioselectivity to exist in the teratogenicity of thalidomide, it could result from fast hydrolysis to chirally stable teratogenic metabolites.