28854-96-8

Basic information

• Product Name: Thymine
• Synonyms: (O~5~'-~3~H)thymidine
• CAS NO: 28854-96-8
• Molecular Formula: C5H6N2O2
• Molecular Weight: 126.11334
• EINECS: -0
• Mol File: 28854-96-8.mol
• Article Data: 227

Chemical Properties

• Boiling Point: °Cat760mmHg
• Flash Point: °C
• Appearance: /
• Density: g/cm³
• CAS DataBase Reference: Thymine(CAS DataBase Reference)
• NIST Chemistry Reference: Thymine(28854-96-8)
• EPA Substance Registry System: Thymine(28854-96-8)

Safety Data

• Hazardous Substances Data: 28854-96-8(Hazardous Substances Data)

Upstream product

• 4784-41-2 1-(2-deoxy-3,5-di-O-p-toluoyl-α-D-erythro-pentofuranosyl)thymine 
• 35898-26-1 4-Methyl-benzoic acid (2R,3S,5S)-3-hydroxy-5-(5-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-tetrahydro-furan-2-ylmethyl ester 
• 3056-13-1 3',5'-di-O-p-toluoyl-α-2'-deoxythymidine 
• 4449-31-4 1-[O³,O⁵-bis-(4-chloro-benzoyl)-α-D-erythro-2-deoxy-pentofuranosyl]-5-methyl-1H-pyrimidine-2,4-dione 
• 50-89-5 thymidine 
• 153737-54-3 3'-5'-di-O-acetyl-α-D-thymidine 
• 444810-96-2 3'-O-diphenylacetyl-β-thymidine 
• 4449-39-2 3',5'-di-O-toluoylthymidine 
• 21740-23-8 3,5-O-bis(4-chlorobenzoyl)-2-deoxy-α-D-ribofuranosyl chloride 
• 65-71-4 thymin 
• 7288-28-0 2,4-bis(trimethylsiloxy)-5-methylpyrimidine 
• 3056-13-1 3',5'-di-O-p-toluoyl-2'-deoxythymidine 
• 676598-19-9 methyl 2-deoxy-5-O-(4-methylbenzoyl)-D-erythro-pentofuranoside 
• 78138-12-2 4-Methyl-benzoic acid (2R,3S)-3-benzyloxy-5-chloro-tetrahydro-furan-2-ylmethyl ester 

Downstream Products

• 15981-92-7 2,3'-anhydrothymidine 
• 26543-09-9 Monocrotalic acid 
• 28333-17-7 dehydroretronecine dimethyl ether 
• 133787-49-2 1-((2R,4S,5R)-4-Hydroxy-5-hydroxymethyl-tetrahydro-furan-2-yl)-3-(7-methoxy-6,7-dihydro-5H-pyrrolizin-1-ylmethyl)-5-methyl-1H-pyrimidine-2,4-dione 
• 23291-96-5 monocrotaline pyrrole 
• 93612-84-1 5'-O-<2-(methylthiomethoxymethyl)benzoyl>thymidine 
• 78582-17-9 4-Amino-1-(2-deoxy-β-D-erythropentofuranosyl)-1H-imidazo<4,5-c>pyridine 
• 89178-21-2 2-bromo-2′-deoxyadenosine 
• 87491-50-7 C₄₈H₅₄N₇O₁₄P 
• 87471-38-3 C₅₀H₅₂N₅O₁₄P 
• 70900-98-0 (PhS)2pTp(tc)T 
• 70900-99-1 (4-CH₃OC₆H₄S)2pTp(tc)T 
• 70942-52-8 (4-CH₃OC₆H₄S)2pTp(tc)Tp(tc)T 
• 61892-07-7 C₄₆H₄₆ClN₄O₁₃P 

Relevant articles and documents

Synthetic studies of potential antimetabolites. XI. Syntheses of beta-D-pentofuranosyl-5-methylcytosines.

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Active species for Ce(IV)-induced hydrolysis of phosphodiester linkage in cAMP and DNA

The hydrolysis of cyclic adenosine 3′,5′-monophosphate and 2′-deoxythymidylyl(3′-5′)2′-deoxythymidine by Ce(NH 4)2(NO3)6 was kinetically studied. The rate of hydrolysis was fairly proportional to the concentration of [Ce 2IV (OH)4]4+, showing that this is the catalytically active species. According to quantum-chemical calculation, the two Ce(IV) ions in this [Ce2IV (OH)4] 4+ cluster are bridged by two OH residues. Upon the complex formation with H2PO4- (a model compound for the phosphodiesters), these two Ce(IV) ions bind the two oxygen atoms of the substrate and enhance the electrophilicity of the phosphorus atom. The catalytic mechanism of Ce(IV)-induced hydrolysis of phosphodiesters has been proposed on the basis these results. Copyright Taylor & Francis Group, LLC.

THE USE OF ZINC BROMIDE FOR REMOVAL OF DIMETHOXYTRITYL ETHERS FROM DEOXYNUCLEOSIDES

Zinc bromide has been observed to detritylate specifically 5'-trityldeoxy-deoxynucleosides whereas 3'-trityl ethers are not cleaved.Of additional practical consideration and in contrast to protic acids, no depurination was observed with this reagent.

Synthesis of thymidine from 5-iodo-2'-deoxyuridine

A simple, high yield synthesis of thymidine from 5-iodo-2'-deoxyuridine is described, using tetramethyltin and tetrakis(triphenylphosphine)palladium(0) in hexamethylphosphoric triamide. Likewise, 5-phenyl- and 5-vinyl-2'-deoxyuridine can be obtained, and through reduction of the latter the 5-ethyl analogue is also at hand.

1:1 and 1:2 complexes of Bu4NF and BF3·Et2O: Unique properties as reagents for cleavage of silyl ethers

A new method for removal of trialkylsilyl groups from silyl ethers using Complex A and Complex B, generated from tetrabutylammonium fluoride (TBAF) and BF3·Et2O has been developed. The desilylation by use of these boron complexes is significantly affected by the steric factor on the Si atom and the reagent.

New acid photogenerators based on thioxanthen-9-one sulfonium derivatives for detritylation in the oligonucleotide synthesis

Photochemical activity of a number of cationic thioxanthen-9-one derivatives for the formation of the trityl cation was studied, which resulted in the selection of compounds suitable for photodetritylation. 10-(4-Heptyloxyphenyl)-9-oxo-2-(N,N,N-triethylammonio)methyl-9H-thioxanthenium bis(hexafluorophosphate) and 2-methyl-, 2-(2-methyl-1-propanoyl-2-tosyl)-, 1-chloro-4-propoxy-, and 2,4-diethyl-10-(4-heptyloxyphenyl)-9-oxo-9H- thioxanthenium hexafluorophosphates were found to be photoactivators of detritylation of 5′-O-(4,4′-dimethoxytrityl)thymidine. The detritylation reaction is the most efficient in dichloromethane. 2,4-Diethyl-10-(4-heptyloxyphenyl)-9-oxo-9H-thioxanthenium hexafluorophosphate was used as a detritylation photoactivator in the oligonucleotide synthesis using an automated DNA synthesizer. The yield in the elongation step of the oligonucleotide chain was 98%.

DIALKYL ALUMINIUM CHLORIDE: A REAGENT FOR REMOVAL OF TRITYL GROUP FROM TRITYL ETHERS OF DEOXYNUCLEOSIDES, DEOXYNUCLEOTIDES, AND OLIGODEOXYNUCLEOTIDES

Detritylation of N-acyl-5'-O-tritylated deoxynucleosides, deoxynucleotides, and oligodeoxynucleotides have been quantitatively achieved in minutes at room temperature by using diethylaluminium chloride or diisobutylaluminium chloride.Reactions take place in unpolar solvents in homogeneous phase under completely aprotic conditions.

Photochemical Control of DNA Structure through Radical Disproportionation

Photolysis of an aryl sulfide-containing 5,6-dihydropyrimidine (1) at 350 nm produces high yields of thymidine and products resulting from trapping of a 5,6-dihydrothymidin-5-yl radical by O2 or thiols. Thymidine is believed to result from disproportionation of the radical pair originally generated from C-S bond homolysis of 1 on the microsecond timescale, which is significantly shorter than other photochemical transformations of modified nucleotides into their native forms. Duplex DNA containing 1 is destabilized, presumably due to disruption of π-stacking. Incorporation of 1 within the binding site of the restriction endonuclease EcoRV provides a photochemical switch for turning on the enzyme's activity. In contrast, 1 is a substrate for endonuclease VIII and serves as a photochemical off switch for this base excision repair enzyme. Modification 1 also modulates the activity of the 10-23 DNAzyme, despite its incorporation into a nonduplex region. Overall, dihydropyrimidine 1 shows promise as a tool to provide spatiotemporal control over DNA structure on the miscrosecond timescale.

4-Acetylthio-2,2-dimethyl-3-oxobutyl group as an esterase- And thermo-labile protecting group for oligomeric phosphodiesters

(4-Acetylthio-2,2-dimethyl-3-oxobutyl)-protected oligomeric phosphodiesters 1 and 2 were synthesized and removal of the protecting groups in the presence and absence of hog liver esterase was followed at pH 7.5 and 37 °C. Phosphotriesters 1 and 2 were successfully converted into the desired fully deprotected phosphodiesters 3 and 4, respectively. Some cleavage of internucleosidic P-O bonds took place, which reduced the yield of 3 and 4. Non-enzymatic removal of the protecting group was only modestly retarded by accumulation of negative charge on the molecule. With 1, the half-lives for the departure of the first and second protecting groups were 7.8 and 10.7 h, respectively, and with 2, 6.2 and 7.2 h, respectively. After 4 d, 70% of both starting materials 1 and 2 were converted into the unprotected phosphodiester. The presence of hog liver esterase (2.6 units mL-1) resulted in fast removal of the first protecting group (τ1/2 2.7 min and 36 min with 1 and 2, respectively), but the appearance of fully deprotected 3 and 4 was accelerated only by a factor of 2, consistent with dramatic retardation of the enzymatic reaction upon accumulation of the negative charge.

Selectivity in the catalytic transfer hydrogenolysis of silyl ether protecting groups

Catalytic transfer hydrogenolysis has been used to selectively cleave silyl protecting groups from primary and secondary alcohols, including from thymidine. Ease of cleavage is in the order triethyl >> t-butyldimethyl > triisopropyl > t-butyldiphenyl.

Photogenerator of trichloroacetic acid as a promising detritylation agent for oligonucleotide microarray synthesis

[[4-(4-Methoxyphenyl)-2,6-dinitro-phenyl](phenyl)methyl]-2,2,2-trichloroacetate, which generates trichloroacetic acid when irradiated with light of 405 nm wavelength, has been studied as a detritylation agent in the oligonucleotide microarray synthesis. This agent was shown to be suitable for the deprotection of the 4,4'-dimethoxytrityl group during the solid phase oligonucleotide synthesis.

Participation of an additional 4′-hydroxymethyl group in the cleavage and isomerization of ribonucleoside 3′-phosphodiesters

4′-(Hydroxymethyl)uridylyl-3′,5′-thymidine, an RNA model bearing an extra hydroxymethyl group at the 4′-position of the 3′-linked nucleoside, has been prepared and its cleavage and isomerization reactions studied over a wide pH range (from 0 to 12). Overa

Development of a 32P-postlabeling method for the detection of 1, N2-propanodeoxyguanosine adducts of 2-hexenal in vivo.

2-Hexenal is an alpha,beta-unsaturated carbonyl compound which forms cyclic 1,N2-propano adducts in vitro. The adduct formation in vivo was not reported by others to date. Because this type of adduct is considered promutagenic (2-hexenal is actually mutagenic and genotoxic) and humans are permanently exposed to this compound via vegetarian food, 2-hexenal may play a role in carcinogenicity. To improve the cancer risk assessment, we developed a new 32P-postlabeling technique for this compound and optimized the different steps of the postlabeling procedure. The results of the postlabeling methods are shown. A labeling efficiency of 35%, a recovery of 10% for the synthesized standards, and a detection limit of three 2-hexenal adducts per 10(8) nucleotides was achieved. After gavage of 500 mg/kg of body weight to male Fischer 344 rats, the respective DNA adducts were detected in rat liver DNA. With this study, we demonstrate in vivo adduct formation of 2-hexenal for the first time. Highest adduct levels were found 2 days after gavage, and after 4 days, the level was even higher than after 1 day. No adducts were detected 8 h after gavage. The respective adducts could not be found as a background in tissues of untreated rats or in calf thymus DNA at the limit of detection.

Independent generation of C5′-nucleosidyl radicals in thymidine and 2′-deoxyguanosine

(Chemical Equation Presented) The synthesis of the C5′ tert-butyl ketone of thymidine 1a and 2′-deoxyguanosine 2 is achieved by reaction of 5′-C-cyano derivatives with tert-butyl lithium followed by acid hydrolysis. The 5′R configuration is assigned by X-ray crystal structure determination of an opportunely protected derivative of 1a. The (5′S)-isomers of both nucleosides are not stable, and a complete decomposition occurs in the reaction medium. The photochemistry of 1a and 2 effectively produced the thymidin-5′-yl radical and the 2′-deoxyguanosin-5′-yl radical, respectively. In the thymidine system, the C5′ radical is fully quenched in the presence of a physiological concentration of thiols. In the 2′-deoxyguanosine system, the C5′ radical undergoes intramolecular attack onto the C8-N7 double bond of guanine leading ultimately to the 5′,8-cyclo-2′-deoxyguanosine derivative. The cyclization of the 2′-deoxyguanosin-5′-yl radical occurs with a rate constant of ca. 1 × 106 s-1 and is highly stereoselective affording only the (5′S)-diastereomer.

Nucleoside 2′-deoxyribosyltransferase from psychrophilic bacterium Bacillus psychrosaccharolyticus - Preparation of an immobilized biocatalyst for the enzymatic synthesis of therapeutic nucleosides

Nucleoside 2′-deoxyribosyltransferase (NDT) from the psychrophilic bacterium Bacillus psychrosaccharolyticus CECT 4074 has been cloned and produced for the first time. A preliminary characterization of the recombinant protein indicates that the enzyme is an NDT type II since it catalyzes the transfer of 2′-deoxyribose between purines and pyrimidines. The enzyme (BpNDT) displays a high activity and stability in a broad range of pH and temperature. In addition, different approaches for the immobilization of BpNDT onto several supports have been studied in order to prepare a suitable biocatalyst for the one-step industrial enzymatic synthesis of different therapeutic nucleosides. Best results were obtained by adsorbing the enzyme on PEI-functionalized agarose and subsequent cross-linking with aldehyde-dextran (20 kDa and 70% oxidation degree). The immobilized enzyme could be recycled for at least 30 consecutive cycles in the synthesis of 2′-deoxyadenosine from 2′-deoxyuridine and adenine at 37 °C and pH 8.0, with a 25% loss of activity. High conversion yield of trifluridine (64.4%) was achieved in 2 h when 20 mM of 2′-deoxyuridine and 10 mM 5-trifluorothymine were employed in the transglycosylation reaction catalyzed by immobilized BpNDT at 37 °C and pH 7.5.

4,4',4"-Tris(4,5-dichlorophthalimido)trityl: A New Type of Hydrazine-Labile Group as a Protecting Group of Primary Alcohols

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Unprecedentedly fast DNA hydrolysis by the synergism of the cerium(IV)-praseodymium(III) and the cerium(IV)-neodymium(III) combinations

The most active catalysts for DNA hydrolysis so far have been obtained by using the synergetic cooperation of the cerium(IV) ion with the praseodymium(III) ion. The pseudo first-order rate constant for the hydrolysis of thymidylyl(3'-5')thymidine by the 2:1 combination is 10 times as great as that by the cerium(IV) ion.

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Photolysis and thermolysis of platinum(IV) 2,2′-bipyridine complexes lead to identical platinum(II)-DNA adducts

Two PtIV and two Pt11 complexes containing a 2,2′-bipyridine ligand were treated with a short DNA oligonucleotide under light irradiation at 37 °C or in the dark at 37 and 50 °C. Photolysis and thermolysis of the PtIV complexes led to spontaneous reduction of the PtIV to the corresponding PtII complexes and to binding of PtII 2,2′-bipyridine complexes to N7 of guanine. When the reduction product was [Pt(bpy)Cl2], formation of bis-oligonucleotide adducts was observed, whereas [Pt(bpy)(MeNH 2)Cl]+ gave monoad- ducts, with chloride ligands substituted in both cases. Neither in the dark nor under light irradiation was the reductive elimination process of these PtIV complexes accompanied by oxidative DNA damage. This work raises the question of the stability of photoacti- vatable PtIV complexes toward moderate heating conditions.

REMOVAL OF CYCLIC DI-T-BUTYLSILANEDIYL PROTECTING GROUPS USING TRIBUTYLAMINE HYDROFLUORIDE (TBAHF) REAGENT

Cyclic di-t-butylsilanediyl protecting groups were rapidly and cleanly removed from 3',5'-cyclic silanediyl nucleosides by a mild and convenient reagent, tributylamine hydrofluoride in tetrahydrofuran.

SYNTHESIS AND IMPROVEMENT OF A NUCLEOSIDE ANALOGUE AS AN ANTI-CANCER AND ANTI-VIRAL DRUG

The invention is a drug for anticancer and antiviral therapy, comprising a nucleoside analogue (7) comprising a furan ring irreversibly bound to the RNA/DNA synthesis chain by phosphodiester bonds and having SP3 hybridization, and folic acid (A) bound to the nucleoside analogue (7) comprising furan ring. The synthesis method of the said nucleoside analogue is also contained within the scope of the invention. In this work, a nucleoside-analogue was transformed after converting the furan-ring hybridization from Sp2 to Sp3 to make it more selectivity with different enzymes and linking it via site 5 with the effective folic acid towards entering the substances inside the cells and to become the final compound possessing anti-cancer and anti- virus properties after controlling the replication and reproduction process in DNA.

Meteorite-catalyzed intermoleculartrans-glycosylation produces nucleosides under proton beam irradiation

Di-glycosylated adenines act as glycosyl donors in the intermoleculartrans-glycosylation of pyrimidine nucleobases under proton beam irradiation conditions. Formamide and chondrite meteorite NWA 1465 increased the yield and the selectivity of the reaction