13552-61-9

Basic information

• Product Name: 2-thiolhistidine
• Synonyms: DL-2-Histidinethiol;DL-2-Thiohistidine;DL-2-Thiolhistidine
• CAS NO: 13552-61-9
• Molecular Formula: C₆H₉N₃O₂S
• Molecular Weight: 187.22
• Mol File: 13552-61-9.mol

Chemical Properties

• Boiling Point: 376.3°Cat760mmHg
• Flash Point: 181.4°C
• Appearance: /
• Density: 1.52g/cm³
• Vapor Pressure: 1.06E-06mmHg at 25°C
• Refractive Index: 1.695
• PKA: 2.27±0.10(Predicted)
• CAS DataBase Reference: 2-thiolhistidine(CAS DataBase Reference)
• NIST Chemistry Reference: 2-thiolhistidine(13552-61-9)
• EPA Substance Registry System: 2-thiolhistidine(13552-61-9)

Safety Data

• Hazardous Substances Data: 13552-61-9(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
2-thiolhistidine is used as a pharmaceutical agent for its potential antioxidant and metal-chelating properties. Its ability to modulate cellular redox signaling and regulate the activity of certain enzymes makes it a promising candidate for the development of therapeutic agents for various diseases and medical conditions.
Used in Biochemical Research:
2-thiolhistidine is used as a research tool in biochemical studies for its role in the formation of metal ion-binding sites in proteins and enzymes. It aids scientists in understanding the complex interactions and mechanisms within biological systems, contributing to the advancement of knowledge in the field of biochemistry.
Used in Diagnostic Applications:
2-thiolhistidine can be used in diagnostic applications to assess the levels of certain enzymes or to evaluate the effectiveness of treatments targeting specific biological processes. Its involvement in various biological processes makes it a valuable marker for monitoring health and disease states.
Used in Nutritional Supplements:
Due to its potential antioxidant and metal-chelating properties, 2-thiolhistidine may be used as an ingredient in nutritional supplements to support overall health and well-being. It could potentially help maintain proper cellular function and support the body's natural defense mechanisms against oxidative stress and metal toxicity.

InChI:InChI=1/C6H9N3O2S/c7-4(5(10)11)1-3-2-8-6(12)9-3/h2,4H,1,7H2,(H,10,11)(H2,8,9,12)

Upstream product

• 1027163-92-3 C₁₆H₂₅N₃O₆S 
• 1392219-77-0 C₁₆H₂₅N₃O₆S 
• 89765-68-4 C₁₁H₁₇N₃O₄S 
• 333-20-0 potassium thioacyanate 
• 78397-05-4 L-2,5-diamino-4-oxopentanoic acid dihydrochloride 
• 5934-29-2 L-histidine hydrochloride monohydrate 
• 645-35-2 L-histidine monohydrochloride 
• 507-09-5 tiolacetic acid 
• 71-00-1 L-histidine 
• 6298-07-3 α,δ-dibenzoyl-γ-oxoornithine methyl ester 
• 20898-43-5 4-(2-tert-butoxycarbonylamino-2-methoxycarbonyl-ethyl)-1H-imidazole-1-carboxylic acid tert-butyl ester 
• 17791-51-4 methyl (S)-3-<1-(1,1-dimethylethoxycarbonyl)-1H-imidazol-5-yl>-2-<(1,1-dimethylethoxycarbonyl)amino>propionate 
• 4467-54-3 l-histidine methyl ester dihydrochloride 
• 168292-00-0 methyl (S)-2-<(1,1-dimethylethoxycarbonyl)amino>-3-(2-mercapto-1H-imidazol-4-yl)propionate 

Relevant articles and documents

Short protecting-group-free synthesis of 5-acetylsulfanyl-histidines in water: Novel precursors of 5-sulfanyl-histidine and its analogues

The discovery of a non-enzymatic oxidative introduction of sulfur to the 5-position of histidine is reported, by activation with bromine or NBS followed by reaction with thioacetic acid forming novel 5-acetylsulfanyl-histidine. Complementing the previously developed regioselective oxidative S-introduction to the 2-position of histidine by reaction with cysteine, this surprising finding provides straightforward access in multi-gram quantities to naturally occurring 5-sulfanyl-histidine and its N-methylated analogues, including a hitherto unknown regioisomer of l-ergothioneine.

Ergothioneine in a peptide: Substitution of histidine with 2-thiohistidine in bioactive peptides

Ergothioneine (EGT) is the betaine of 2-thiohistidine (2-thioHis) and may be the last undiscovered vitamin. EGT cannot be incorporated into a peptide because the α-nitrogen is trimethylated, although this would be advantageous as an EGT-like moiety in a peptide would impart unique antioxidant and metal chelation properties. The amino acid 2-thioHis is an analogue of EGT and can be incorporated into a peptide, although there is only one reported occurrence of this in the literature. A likely reason is the harsh conditions reported for protection of the thione, with similarly harsh conditions used in order to achieve deprotection after synthesis. Here, we report a novel strategy for the incorporation of 2-thioHis into peptides in which we decided to leave the thione unprotected. This decision was based upon the reported low reactivity of EGT with 5,5′-dithiobis(2-nitrobenzoic acid) (DTNB), a very electrophilic disulfide. This strategy was successful, and we report here the synthesis of 2-thioHis analogues of carnosine (βAH), GHK-tripeptide, and HGPLGPL. Each of these peptides contain a histidine (His) residue and possesses biological activity. Our results show that substitution of His with 2-thioHis imparts strong antioxidant, radical scavenging, and copper binding properties to the peptide. Notably, we found that the 2-thioHis analogue of GHK-tripeptide was able to completely quench the hydroxyl and ABTS radicals in our assays, and its antioxidant capacity was significantly greater than would be expected based on the antioxidant capacity of free 2-thioHis. Our work makes possible greater future use of 2-thioHis in peptides.

METHOD FOR THE SYNTHESIS OF 2-THIOHISTIDINE AND THE LIKE

Methods for the synthesis of 2-thiohistidine or a derivative thereof of the formula (I), or of a physiologically acceptable salt, a tautomer, a stereoisomer or a mixture of stereoisomers in any proportions thereof, from a compound of the formula (II) or a physiologically acceptable salt, a tautomer, a stereoisomer or a mixture of stereoisomers in any proportions thereof, by cleavage reaction in the presence of a thiol at a temperature higher than or equal to 60° C. The invention also relates to compounds of the formula (II) and a method for the synthesis thereof.

Cysteine as a sustainable sulfur reagent for the protecting-group-free synthesis of sulfur-containing amino acids: Biomimetic synthesis of l-ergothioneine in water

Biomass-derived cysteine was used as a sustainable sulfur source for the synthesis of rare sulfur-containing amino acids, such as l-ergothioneine (4), which might be a new vitamin, and various l- or d-2-thiohistidine compounds. Key in this simple, one-pot two-step procedure in water is a bromine-induced regioselective introduction of cysteine followed by a novel thermal cleavage reaction in the presence of thiols, a safer alternative to hazardous red phosphorus. Besides avoiding hazardous sulfur reagents, the new protecting-group-free approach reduces drastically the total number of steps, compared to described procedures. The main drawback, i.e. handling of liquid bromine as an activating and oxidizing reagent in water, was addressed by evaluating four alternative methods using in situ generation of bromine or HOBr, and first encouraging results are described.

PROCESS FOR THE SYNTHESIS OF L-(+)-ERGOTHIONEINE

This invention relates to a novel process for the preparation of optically pure L-(+)-ergothioneine. The process for the chemical synthesis of L-ergothioneine comprises steps which consist of reacting L-histidine alkyl ester with an acid halide, chloroformate or pyrocarbonate in the presence of a base, hydrolysis of the alkyl-(S,Z)-2,4,5-triamidopent-4-enoate to obtain a (S)-alkyl 2,5-diamido-4-oxopentanoate, acid catalyzed hydrolysis of the (S)-alkyl 2,5-diamido-4-oxopentanoate followed by reaction with a metal thiocyanate to obtain the thiohistidine, protection of the sulfur of thiohistidine as the tert-butyl thioether, dialkylation of the primary amine to obtain a tertiary amine, quaternization of the tertiary amine, and removal of the protecting group to obtain the desired (S)-3-(2-mercapto-1H-imidazol-5-yl)-2-(trialkylammonio)propanoate (I). This process affords a better yield and is capable of practical application at large scale.

Synthesis of L-(+)-ergothioneine

The first synthesis of L-(+)-ergothioneine (1), a rare natural amino acid, is described. The key step is the direct transformation of the imidazole derivative 11 into imidazole-2-thione 12. This reaction consists of the cleavage and the re-formation of imidazole ring (ANRORC) with phenyl chlorothionoformate via a Bamberger-type intermediate. The conditions used are mild enough to preserve the asymmetric center at the 1a-carbon. The release of enantiomerically pure L-ergothioneine (1) from the ammonium derivative 15 was performed under acidic conditions to avoid the very easy racemization of the betaine function. An efficient and high-yield sypthesis of 2-mercapto-L-histidine (2) which uses the new imidazole-2-thione formation reaction is also described.