64165-64-6

Usage

Uses

Used in Pharmaceutical Industry:
DL-Propargylglycine is used as an inhibitor for the enzyme cystathione-γ-lyase, which plays a crucial role in hydrogen sulfide biosynthesis. By inhibiting this enzyme, DL-Propargylglycine can help regulate H2S production, which has been linked to various physiological and pathological processes. This application is particularly relevant in the development of treatments for conditions associated with abnormal H2S levels.
Used in Medical Research:
DL-Propargylglycine is used as a research tool to study the role of hydrogen sulfide in various biological processes. Its ability to inhibit H2S production makes it a valuable compound for investigating the effects of H2S on cellular functions, signaling pathways, and disease progression. This application is essential for advancing our understanding of H2S biology and its potential as a therapeutic target.
Used in Inflammation Management:
DL-Propargylglycine is used as an anti-inflammatory agent in rodent models of inflammation, such as carrageenan-induced hindpaw edema. Its ability to reduce inflammation can be beneficial in the development of treatments for inflammatory conditions, including arthritis, autoimmune diseases, and other disorders characterized by excessive inflammation.
Used in Nephrotoxicity Prevention:
DL-Propargylglycine is used to ameliorate gentamycin-induced nephrotoxicity, a common side effect of gentamycin, an antibiotic used to treat various bacterial infections. By reducing the toxic effects of gentamycin on the kidneys, DL-Propargylglycine can help improve patient outcomes and minimize the risk of kidney damage associated with gentamycin use.

Synthesis Reference(s)

Journal of the American Chemical Society, 76, p. 3484, 1954 DOI: 10.1021/ja01642a036Tetrahedron Letters, 22, p. 1787, 1981 DOI: 10.1016/S0040-4039(01)90439-3

Biochem/physiol Actions

DL-Propargylglycine (PAG) is an irreversible inhibitor of the enzyme cystathionine γ-lyase (GCL), a key enzyme involved in glutathione synthesis and the metabolic transsulfuration pathway which regulates homocysteine concentration and mediates cysteine synthesis. Treatment of animal disease models with PAG was shown to alleviate symptoms of diseases that impair the formation or action of hydrogen sulfide (H2S).

References

1) Dam et al. (2012), Inhibition of cystathione gamma-lyase and the biosynthesis of endogenous hydrogen sulphide ameliorates gentamicin-induced nephrotoxicity; Eur. J. Pharmacol., 685 165 2) Mok et al. (2004), Role of hydrogen sulphide in haemorrhagic shock in the rat: protective effect of inhibitors of hydrogen sulphide biosynthesis; Br. J. Pharmacol., 143 881 3) Bhatia et al. (2005),Hydrogen sulphide is a mediator of carrageenan-induced hindpaw edema in the rat; Br. J. Pharmacol., 145 141

InChI:InChI=1/C5H7NO2.ClH/c1-2-3-4(6)5(7)8;/h1,4H,3,6H2,(H,7,8);1H

Upstream product

• 23235-02-1 N-Acetyl-α-propargylglycine 
• 78342-50-4 (R)-2-amino-4-pentynoic acid methyl ester 
• 106-96-7 propargyl bromide 
• 56-40-6 glycine 
• 718596-26-0 2-amino-4-pentynoic acid amide 
• 50428-03-0 D,L-propargylglycine 
• 81136-58-5 (2S,5R)-2-(3,4-Dimethoxy-benzyl)-3,6-dimethoxy-2-methyl-5-prop-2-ynyl-2,5-dihydro-pyrazine 
• 788814-11-9 (R)-2-amino-4-pentynoic acid amide 
• 207459-88-9 (R)-2-(2,2,5,7,8-Pentamethyl-chroman-6-sulfonylamino)-5-trimethylsilanyl-pent-4-ynoic acid 
• 180311-20-0 2-(Benzhydrylidene-amino)-pent-4-ynoic acid 2'-hydroxy-[1,1']binaphthalenyl-2-yl ester 
• 78342-46-8 (2R,5S)-5-isopropyl-3,6-dimethoxy-2-propargyl-2,5-dihydropyrazine 
• 23235-02-1 N-Acetyl-D-α-propargylglycine 

Downstream Products

• 61172-66-5 Boc-L-Pra-OH 
• 211054-15-8 (R)-2-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-pent-4-ynoic acid 
• 885104-37-0 (R)-2-(3,4-dichlorobenzenesulfonamido)pent-4-ynoic acid 
• 61172-66-5 (R)-2-((tert-butoxycarbonyl)amino)pent-4-ynoic acid 
• 208709-76-6 (R)-N-Boc-propargylglycine methyl ester 
• 884048-31-1 C₇H₁₁NO₂*ClH 
• 1215092-10-6 C₁₄H₁₆N₂O₃ 
• 2862-51-3 (3S,6S)-3,6-dibenzylpiperazine-2,5-dione 
• 1246928-02-8 tert-butyl N₂-(tert-butoxycarbonyl)-N₆-((R)-2-tert-butoxycarbonylamino-3-(1-(7-hydroxy-2-oxo-2H-chromen-3-yl)-1H-1,2,3-triazol-4-yl)propanoyl)lysinate 
• 885104-33-6 (R)-(2-benzenesulfonamido)pent-4-ynoic acid 
• 87155-95-1 D-alanyl-D-propargylglycine trifluoroacetate 
• 93836-36-3 N-Boc-D-Ala-D-ppGly-O-t-Bu 
• 211054-04-5 (R)-2-(Toluene-4-sulfonylamino)-pent-4-ynoic acid methyl ester 

Relevant academic research and scientific papers

DL-propargyl glycine intermediate and preparation method thereof, and propargyl glycine preparation method based on intermediate

The invention relates to the field of amino acid preparation, in particular to a DL-propargyl glycine intermediate, a preparation method of the DL-propargyl glycine intermediate and a preparation method of propargyl glycine based on the DL-propargyl glycine intermediate. The preparation method of the DL-propargyl glycine intermediate comprises three steps of condensation, saponification and hydrolysis, and then corresponding derivatives can be obtained through a chemical resolution method and an enzyme resolution method respectively. According to the preparation method, the reaction time is shortened; the reaction is more thorough, thepreparation method of DL-propargyl glycine can be obtained through the reaction, two methods for preparing derivatives of D-propargyl glycine and L-propargylglycine are obtained at the same time, the prepared product is high in purity, secondary refining is not needed, the production cost is reduced, and industrial large-scale production is facilitated.

Synthesis of ω-(hetero)arylalkynylated α-amino acid by sonogashira-type reactions in aqueous media

(Chemical Equation Presented) Mild conditions are described that allow the palladium-catalyzed cross-coupling of Cα-alkynylated glycine with a wide variety of electron-rich and electron-poor aryl and heteroaryl halides in aqueous media.

A Biocatalytic Route to Enantiomerically Pure Unsaturated α-H-α-Amino Acids

A set of both enantiomeric forms of non-proteinogenic, unsaturated α-H-α-amino acids was efficiently synthesized using a biocatalytic pathway. This route involved the straightforward synthesis of the required unsaturated amino acid amides, followed by resolution with an aminopeptidase present in Pseudomonas putida ATCC 12633 and/or a genetically modified organism, leading to the (S)-acids and (R)-amides. Undesired amino acid racemase activity was identified in the wild-type strain, which was absent in the newly developed organism. The (R)-amides were hydrolyzed under mild conditions using an amidase present in whole cells from Rhodococcus erythropolis NCIMB 11540 to the (R)-acids. The viability of this procedure was demonstrated with the multi-gram synthesis of a variety of unsaturated amino acids in excellent enantiopurity.

Pd-catalyzed cyclization reactions of acetylene-containing α-amino acids

Acetylene-containing amino acids, obtained in enantiopure form via an enzymatic resolution process, serve as versatile intermediates in the synthesis of various highly functionalized heterocycles. The key transformations, intramolecular OC- and NC-bond formation, proceed via Pd- catalysis.

Synthesis of the suicide substrate D-propargylglycine stereospecifically labelled with deuterium and investigation of its oxidation by D-amino acid oxidase

Stereospecifically deuteriated samples of D-propargylglycine 1 have been prepared by reaction of the labelled Pmc-protected aziridine free acids 22 with a lithium acetylide followed by deprotection. These samples have been used to show that D-amino acid oxidase, in converting D-propargylglycine to the lactone 5, deprotonates C-3 in a non-stereospecific manner. This strongly supports the idea that non-enzymic deprotonation is a key step in the formation of this compound.

Stereoselective, nonracemic synthesis of ω-borono-α-amino acids

ω-Unsaturated α-amino acids are synthesized through condensation of allyl and propargyl bromides or of 9-bromoundecene with a Ni(II) complex of the Schiff base derived from glycine and BPB. Hydroboration with Ipc2BH followed by oxidation with acetaldehyde affords enantiomerically pure ω- borono-α-aminocarboxylic acids.

Asymmetric synthesis of uncommon α-amino acids by diastereoselective alkylations of a chiral glycine equivalent

For the purpose of practical preparations of a variety of enantiomerically pure uncommon α-amino acids, alkylations of the chiral glycine equivalent 5, which possesses axially chiral binaphthol as an auxiliary, with several electrophiles were investigated. The alkylation proceeded smoothly in satisfactory chemical yield with high diastereo-selectivities to give protected α-amino acid derivatives. The free hydroxyl group of the auxiliary played an important role for the induction of diastereoselectivity. Using (S)-1,1'-binaphthalene-2,2'-diol as a chiral auxiliary, D-α-amino acid derivatives having the unnatural (R)-configuration were predominantly obtained. Some of the alkylated products were converted into free non- proteinogenic D-α-amino acids.

Synthesis of Stereospecifically Labelled D-Prop-2-ynylglycine and Investigation of the Action of D-Amino Acid Oxidase

Stereospecifically deuteriated samples of D-prop-2-ynylglycine 1 are synthesised by reaction of the labelled aziridines 13 with a carbon nucleophile followed by deprotection; incubation of these samples with D-amino acid oxidase indicates that, in formation of the lactone 5, deprotonation at C-3 is non-stereospecific, strongly supporting non-enzymatic deprotonation as a key step in the formation of this compound.

Chloroanalyland propargylglycyl dipeptides. Suicide substrate containing antibacterials

A set of dipeptides containing the amino acid residues β-chloroalanine and propargylglycine, which are mechanism-based inactivators of purified microbial enzymes (alanine racemase and cystathionine γ-synthase, respectively), have been synthesized, and their antibacterial properties in vitro have been evaluated. Dipeptides containing a single β-chloro-L-alanyl residue (e.g., 3, 5, 9, and 10) or a single L-propargylglycyl residue (e.g., 12 and 15) are potent antibacterials. The in vitro antibiotic activity of β-chloro-L-alanine and of L-propargylglycine is increased as much as 4000-fold by incorporation of these residues into a dipeptide. Compounds that contain only a single enzyme-inactivating amino acid together with a second L-alanyl residue (3, 5, 12, and 15) have a restricted range of activity: of the species tested, only Streptococcus agalactiae, Staphylococcus aureus, and Staphylococcus epidermidis are sensitive. However, peptides that contain two suicide-substrate residues [e.g., β-Cl-LAla-β-Cl-LAla (8) or LppGly-LppGly (18)] are broad-spectrum antibacterials; as many as 12 different species of the 16 surveyed are sensitive. Dipeptides that contain an amino-terminal L-methionyl (9) or an L-norvalyl (10) residue and a carboxy-terminal β-chloro-L-alanyl unit are also effective against a large number of organisms; the spectra of activity are like those seen for 8 and 18. A 'mixed' dipeptide [β-Cl-LAla-LppGly, (21)] gives apparent synergism of antibiotic action of β-chloro-L-alanine and of L-propargylglycine when these two residues are incorporated into a single structure. Peptides of the D,D configuration (4, 6, 13, 16, and 20) and ones of L,D stereochemistry (e.g., 7) are not antibacterials. Peptides containing one (11 and 14) and two (17) D,L-propargylglycyl residues are unresolved sets of diastereomers; the mixtures of compounds are between two- and fourfold less active than the corresponding resolved L,L dipeptides (12, 15, and 18). These findings are consistent with a mechanism of action for these antibiotics involving stereoselective processing of the peptidyl unit in vivo.