23235-01-0

Basic information

• Product Name: L-Propargylglycine
• Synonyms: (S)-2-AMINO-4-PENTYNOIC ACID;RARECHEM BK PT 0255;(2R)-2-Aminopent-4-ynoic acid;H-GLY(PROPARGYL)-OH;H-PRA-OH;H-PRA-OH HCL;H-PROPARGYL-GLYCINE;H-PROPARGYL-GLY-OH
• CAS NO: 23235-01-0
• Molecular Formula: C₅H₇NO₂
• Molecular Weight: 113.11
• Product Categories: Unusual amino acids;Amino Acids;Antibiotics
• Mol File: 23235-01-0.mol

Chemical Properties

• Boiling Point: 272.052 °C at 760 mmHg
• Flash Point: 118.333 °C
• Appearance: White to pale yellow/Powder
• Density: 1.21 g/cm³
• Vapor Pressure: 0.00174mmHg at 25°C
• Refractive Index: 1.512
• Storage Temp.: 2-8°C
• PKA: 2.04±0.10(Predicted)
• BRN: 2347861
• CAS DataBase Reference: L-Propargylglycine(CAS DataBase Reference)
• NIST Chemistry Reference: L-Propargylglycine(23235-01-0)
• EPA Substance Registry System: L-Propargylglycine(23235-01-0)

Safety Data

• Safety Statements: 22-24/25
• WGK Germany: 3
• F: 10
• Hazardous Substances Data: 23235-01-0(Hazardous Substances Data)

Usage

Chemical Properties

White powder

Enzyme inhibitor

This alkynyl amino acid and mechanism-based inhibitor (FW = 113.11 g/mol; CAS 23235-01-0), also known as (S)-2-amino-4-pentynoic acid, irreversibly inactivates γ-cystathionase (an enzyme that also catalyzes the synthesis of the metabolic signaling gas, H2S, See also Hydrogen Sulfide), acting as a Michael addition type suicide inhibitor of cystathionine γ-lyase, cystathionine γ-synthase, alanine aminotransferase, and methionine γ-lyase. Propargylglycine inactivates γ-cystathionase with pseudo-first-order kinetics and incorporation of 1 mol inhibitor per 80 kDa enzyme. When studied in vivo, inactivation of cystathionine γ-lyase in rat kidney was less than that in the liver, owing to the presence of a higher cysteine concentration in kidney. L-Propargylglycine was found to inactivate pig heart L-alanine transaminase (EC 2.6.1.2) at 37o C with a Ki = 3.9 mM, an observed maximal first order rate constant, kinact = 0.26 min–1, a minimal stoichiometric ratio necessary for inactivation of 2.7 L-propargylglycine molecules/enzyme subunit, with 2.2 molecules/subunit undergoing transamination before inactivation ensues. Experimental cystathioninuria, induced in rats by administration of D,L-propargylglycine, results in the formation of the cystathionine metabolites, cystathionine ketimine and perhydro-1,4-thiazepine-3,5-dicarboxylic acid, in various regions of the brain. L-Propargylglycine irreversibly inactivates proline dehydrogenase, which catalyzes the first step of proline catabolism, oxidizing proline to pyrroline-5-carboxylate. The 1.9-? resolution structure of the inactivated Thermus thermophilus enzyme shows that N5 of the flavin cofactor is covalently connected to the e-amino group of Lys-99 via a three-carbon linkage, consistent with the mass spectral analysis of the inactivated enzyme. The isoalloxazine ring has a butterfly angle of 25o, suggesting the cofactor is reduced. Two mechanisms, both involving oxidation to N-propargyliminoglycine, can account for these properties. L-Propargylglycine irreversibly inhibits L-amino acid oxidase from the venom of Crotalus adamanteus (Eastern diamondback rattlesnake) and Crotalus atrox (Western diamondback rattlesnake) in a dose- and timedependent manner that was blocked by the substrate L-phenylalanine. Other targets include methionineγ-lyase and UDP-Nacetylmuramate: L-alanine ligase, or L-alanine-adding enzyme, or UDP-Nacetylmuramoyl- L-alanine synthetase.

Purification Methods

The acid crystallises readily when ~4g in 50mL H2O are treated with absolute EtOH at 4o/3hours, and is collected, washed with cold absolute EtOH and Et2O and dried in a vacuum. Also, it recrystallises from aqueous Me2CO, RF on SiO2 TLC plates with n-BuOH/H2O/AcOH (4:1:1) is 0.26. The racemate has m 238-240o. [Leukart et al. Helv Chim Acta 59 2181 1976, Eberle & Zeller Helv Chim Acta 68 1880 1985, Jansen et al. Recl Trav Chim Pays-Bas 88 819 1969.] It is a suicide inhibitor of -cystathionase and other enzymes [Washtier & Abeles Biochemistry 16 2485 1977, Shinozuka et al. Eur J Biochem 124 377 1982].

InChI:InChI=1/C5H7NO2/c1-2-3-4(6)5(7)8/h1,4H,3,6H2,(H,7,8)/t4-/m0/s1

Upstream product

• 23235-02-1 N-Acetyl-α-propargylglycine 
• 78342-46-8 (2R,5S)-5-isopropyl-3,6-dimethoxy-2-propargyl-2,5-dihydropyrazine 
• 180311-20-0 2-(Benzhydrylidene-amino)-pent-4-ynoic acid 2'-hydroxy-[1,1']binaphthalenyl-2-yl ester 
• 106-96-7 propargyl bromide 
• 56-40-6 glycine 
• 207459-89-0 (S)-2-(2,2,5,7,8-Pentamethyl-chroman-6-sulfonylamino)-5-trimethylsilanyl-pent-4-ynoic acid 
• 23235-02-1 N-Acetyl-D-α-propargylglycine 
• 78342-50-4 (R)-2-amino-4-pentynoic acid methyl ester 
• 207459-88-9 (R)-2-(2,2,5,7,8-Pentamethyl-chroman-6-sulfonylamino)-5-trimethylsilanyl-pent-4-ynoic acid 
• 718596-26-0 2-amino-4-pentynoic acid amide 
• 788814-11-9 (R)-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 

Downstream Products

• 71460-15-6 2-amino-pent-4-ynoic acid tert-butyl ester 
• 71460-02-1 methyl (2S)-2-(tert-butoxycarbonylamino)pent-4-ynoate 
• 61172-62-1 (S)-2-(1,3-dioxo-1,3-dihydroisoindol-2-yl)pent-4-ynoic acid 
• 1261352-25-3 N-(tert-butoxycarbonyl)-3-{1-[(2S)-1-methoxy-1-oxo-3-phenylpropan-2-yl]-1H-1,2,3-triazol-4-yl}-L-alanine 
• 1261352-28-6 methyl N-(tert-butoxycarbonyl)-3-{1-[(2S)-1-methoxy-1-oxo-3-phenylpropan-2-yl]-1H-1,2,3-triazol-5-yl}-L-alaninate 
• 1261352-18-4 3-[1-(carboxymethyl)-1H-1,2,3-triazol-4-yl]-L-alanine hydrochloride 
• 1261352-19-5 3-{1-[(1S)-1-carboxy-2-phenylethyl]-1H-1,2,3-triazol-4-yl}-L-alanine hydrochloride 
• 1261352-21-9 3-[1-(carboxymethyl)-1H-1,2,3-triazol-5-yl]-L-alanine hydrochloride 
• 1261352-22-0 3-{1-[(1S)-1-carboxy-2-phenylethyl]-1H-1,2,3-triazol-5-yl}-L-alanine hydrochloride 
• 1261352-29-7 C₁₉H₂₄N₄O₆ 
• 1261352-30-0 C₁₉H₂₄N₄O₆ 
• 198561-07-8 Fmoc-L-propargyl-Gly-OH 
• 869116-13-2 Cbz-L-propargylglycine-OH 
• 1217669-02-7 (S)-3-{[((9H-fluoren-9-yl)methoxy)carbonyl]amino}hex-5-ynoic acid 

Relevant articles and documents

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.

A chiral amino acid preparation method

The invention relates to a method for preparing a compound (OMLT-01). The method of the invention comprises the following steps: mixing the compound (OMLT-A) with liquor of sodium hydroxide in an amide solvent, cooling down to 0-10 DEG C, and dropwise add

An Alternative Scalable Process for the Synthesis of the Key Intermediate of Omarigliptin

An alternative scalable process for the synthesis of the key intermediate of omarigliptin is described. The asymmetric synthesis relies on the initial diastereoselective alkylation and subsequent aluminum-catalyzed substrate-controlled Meerwein-Ponndorf-Verley reduction. A highly regioselective 5-exo-dig iodocyclization followed to afford 11b, which was then subjected to ring-opening cycloetherification to give product 1 with >99:1 dr and >99% ee in 31.2% overall yield in nine steps. This synthetic strategy has been successfully applied for multikilogram scale production.

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.

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.

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.

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.