4546-70-7

Usage

Uses

Used in Biomedical Research:
2,6-Diaminopurine 2'-deoxyriboside is used as a research tool for studying the incorporation of unnatural nucleotides into mutant tRNA and proteins. This helps in understanding the mechanisms of DNA metabolism and the potential applications of nucleoside analogs in various biological processes.
Used in Analytical Studies:
2,6-Diaminopurine 2'-deoxyriboside is used as an analyte in analytical studies to investigate the interactions between nucleoside analogs and biological systems. This aids in the development of new methods for detecting and analyzing nucleotide incorporation in various applications.
Used in Pharmaceutical Development:
2,6-Diaminopurine 2'-deoxyriboside has potential applications in the development of new pharmaceuticals targeting DNA metabolism. Its ability to interfere with DNA synthesis and function makes it a promising candidate for the creation of drugs that can modulate cellular processes and treat diseases related to abnormal DNA activity.

Upstream product

• 951-78-0 2'-deoxyuridine 
• 1904-98-9 2,6-diaminopurine 
• 50-89-5 thymidine 
• 81102-46-7 2,6-diamino-8-bromo-9-(2'-O-tosyl-β-D-ribufuranosyl)-purine 
• 961-07-9 2'-Deoxyguanosine 
• 890-38-0 2-deoxyinosine 
• 38925-80-3 2,6-Dichloro-9-(2-deoxy-3,5-di-O-p-toluoyl-β-D-erythro-pentofuranosyl)-purine 
• 1904-98-9 2,6-diaminopurine 
• 79999-39-6 2',3',5'-tri-O-acetyl-2-chloroadenosine 
• 37070-11-4 8,2'-anhydro-8-mercaptoguanosine 
• 81102-48-9 2-acetamido-8,2'-anhydro-6-chloro-8-mercapto-9-(3',5'-O-diacetyl-β-D-arabinofuranosyl)purine 
• 81102-44-5 9-(β-D-ribofuranosyl)-2,6-diamino-8-bromopurine 
• 2096-10-8 adenosine-2-amine 
• 87791-88-6 3′,5′-(1,1,3,3-tetraisopropyl-1,3-disiloxan-1,3-yl)-9-(β-D-ribofuranosyl)purin-2,6-diamine 

Downstream Products

• 156549-47-2 N²,N⁶-bis(phenoxyacetyl)-2,6-diamino-9-(β-D-2-deoxyribofuranosyl) purine 
• 961-07-9 2'-deoxyguanosine 
• 776323-97-8 C₂₆H₂₂N₆O₅ 
• 583047-62-5 9-(3-O-tert-butyldimethylsilyl-2-deoxy-ribo-pentofuranosyl)-2,6-dibenzamidopurine 
• 583047-64-7 9-(3-O-tert-butyldimethylsilyl-2-deoxy-4-C-hydroxymethyl-ribo-pentofuranosyl)-2,6-dibenzamidopurine 
• 583047-66-9 9-(3,5-di-O-tert-butyldimethylsilyl-2-deoxy-4-C-hydroxymethyl-ribo-pentofuranosyl)-2,6-dibenzamidopurine 
• 583047-63-6 C₄₅H₄₀N₆O₇ 
• 583047-65-8 C₅₂H₅₆N₆O₈Si 
• 583047-67-0 9-(3,5-di-O-tert-butyldimethylsilyl-4-C-cyano-2-deoxy-ribo-pentofuranosyl)-2,6-dibenzamidopurine 
• 676458-04-1 9-(3,5-di-O-tert-butyldimethylsilyl-2-deoxy-4-C-ethynyl-ribo-pentofuranosyl)-2,6-dibenzamidopurine 
• 1904-98-9 2,6-diaminopurine 

Relevant academic research and scientific papers

6-O-(Pentafluorophenyl)-2'-deoxyguanosine: A Versatile Synthon for Nucleoside and Oligonucleotide Synthesis

The 6-O-(pentafluorophenyl)-2'-deoxyguanosine derivative 2a can be used to generate in high yield 6-O-methyl-2'-deoxyguanosine, 2,6-diamino-9-(2-deoxy-β-D-erythro-pentofuranosyl)purine, and related derivatives.Further, after appropriate protection and derivatization, 2a can be incorporated into oligonucleotides and there used for postsynthetic oligonucleotide modification.This approach is particularly useful for preparation of oligonucleotides containing 2,6-diaminopurine residues or their 6-alkylamino derivatives.In addition, reaction of 2a, or oligonucleotides containing it, with 4-(dimethylamino)pyridine (DMAP) gives a fluorescent guanine-DMAP adduct.

Thermodynamic Reaction Control of Nucleoside Phosphorolysis

Nucleoside analogs represent a class of important drugs for cancer and antiviral treatments. Nucleoside phosphorylases (NPases) catalyze the phosphorolysis of nucleosides and are widely employed for the synthesis of pentose-1-phosphates and nucleoside analogs, which are difficult to access via conventional synthetic methods. However, for the vast majority of nucleosides, it has been observed that either no or incomplete conversion of the starting materials is achieved in NPase-catalyzed reactions. For some substrates, it has been shown that these reactions are reversible equilibrium reactions that adhere to the law of mass action. In this contribution, we broadly demonstrate that nucleoside phosphorolysis is a thermodynamically controlled endothermic reaction that proceeds to a reaction equilibrium dictated by the substrate-specific equilibrium constant of phosphorolysis, irrespective of the type or amount of NPase used, as shown by several examples. Furthermore, we explored the temperature-dependency of nucleoside phosphorolysis equilibrium states and provide the apparent transformed reaction enthalpy and apparent transformed reaction entropy for 24 nucleosides, confirming that these conversions are thermodynamically controlled endothermic reactions. This data allows calculation of the Gibbs free energy and, consequently, the equilibrium constant of phosphorolysis at any given reaction temperature. Overall, our investigations revealed that pyrimidine nucleosides are generally more susceptible to phosphorolysis than purine nucleosides. The data disclosed in this work allow the accurate prediction of phosphorolysis or transglycosylation yields for a range of pyrimidine and purine nucleosides and thus serve to empower further research in the field of nucleoside biocatalysis. (Figure presented.).

Enzymatic Synthesis of Therapeutic Nucleosides using a Highly Versatile Purine Nucleoside 2’-DeoxyribosylTransferase from Trypanosoma brucei

The use of enzymes for the synthesis of nucleoside analogues offers several advantages over multistep chemical methods, including chemo-, regio- and stereoselectivity as well as milder reaction conditions. Herein, the production, characterization and utilization of a purine nucleoside 2’-deoxyribosyltransferase (PDT) from Trypanosoma brucei are reported. TbPDT is a dimer which displays not only excellent activity and stability over a broad range of temperatures (50–70 °C), pH (4–7) and ionic strength (0–500 mM NaCl) but also an unusual high stability under alkaline conditions (pH 8–10). TbPDT is shown to be proficient in the biosynthesis of numerous therapeutic nucleosides, including didanosine, vidarabine, cladribine, fludarabine and nelarabine. The structure-guided replacement of Val11 with either Ala or Ser resulted in variants with 2.8-fold greater activity. TbPDT was also covalently immobilized on glutaraldehyde-activated magnetic microspheres. MTbPDT3 was selected as the best derivative (4200 IU/g, activity recovery of 22 %), and could be easily recaptured and recycled for >25 reactions with negligible loss of activity. Finally, MTbPDT3 was successfully employed in the expedient synthesis of several nucleoside analogues. Taken together, our results support the notion that TbPDT has good potential as an industrial biocatalyst for the synthesis of a wide range of therapeutic nucleosides through an efficient and environmentally friendly methodology.

THERMOSTABLE BIOCATALYST COMBINATION FOR NUCLEOSIDE SYNTHESIS

The present invention relates to a transglycosylation method for the preparation of natural and synthetic nucleosides using a uridine phosphorylase (PyNPase, E.C. 2.4.2.3), a purine nucleoside phosphorylase (PNPase, E.C. 2.4.2.1), or a combination thereof. These biocatalysts may be used as such, or by means of host cells transformed with vectors comprising recombinant DNA gene derived from hyperthermophilic archaea and encoding for the PyNPase and PNPase enzymes.

2-Substituted dATP Derivatives as Building Blocks for Polymerase-Catalyzed Synthesis of DNA Modified in the Minor Groove

2′-Deoxyadenosine triphosphate (dATP) derivatives bearing diverse substituents (Cl, NH2, CH3, vinyl, ethynyl, and phenyl) at position 2 were prepared and tested as substrates for DNA polymerases. The 2-phenyl-dATP was not a substrate for DNA polymerases, but the dATPs bearing smaller substituents were good substrates in primer-extension experiments, producing DNA substituted in the minor groove. The vinyl-modified DNA was applied in thiol–ene addition and the ethynyl-modified DNA was applied in a CuAAC click reaction to form DNA labelled with fluorescent dyes in the minor groove.

Synthesis of 2,6-dihalogenated purine nucleosides by thermostable nucleoside phosphorylases

The enzymatic transglycosylation of 2,6-dichloropurine (26DCP) and 6-chloro-2-fluoropurine (6C2FP) with uridine, thymidine and 1-(β-D-arabinofuranosyl)-uracil as the pentofuranose donors and recombinant thermostable nucleoside phosphorylases from G. thermoglucosidasius or T. thermophilus as biocatalysts was studied. Selection of 26DCP and 6C2FP as substrates is determined by their higher solubility in aqueous buffer solutions compared to most natural and modified purines and, furthermore, synthesized nucleosides are valuable precursors for the preparation of a large number of biologically important nucleosides. The substrate activity of 26DCP and 6C2FP in the synthesis of their ribo- and 2′-deoxyribo-nucleosides was closely similar to that of related 2-amino- (DAP), 2-chloro- and 2-fluoroadenines; the efficiency of the synthesis of β-D-arabinofuranosides of 26DCP and 6C2FP was lower vs. that of DAP under similar reaction conditions. For a convenient and easier recovery of the biocatalysts, the thermostable enzymes were immobilized on MagReSyn epoxide beads and the biocatalyst showed high catalytic efficiency in a number of reactions. As an example, 6-chloro-2-fluoro-(β-D-ribofuranosyl)-purine (9), a precursor of various antiviral and antitumour drugs, was synthesized by the immobilized enzymes at 60°C under high substrate concentrations (uridine:purine ratio of 2:1, mol). The synthesis was successfully scaled-up [uridine (2.5 mmol), base (1.25 mmol); reaction mixture 50 mL] to afford 9 in 60% yield. The reaction reveals the great practical potential of this enzymatic method for the efficient production of modified purine nucleosides of pharmaceutical interest.

Preparation of the 2′-deoxynucleosides of 2,6-diaminopurine and isoguanine by direct glycosylation

Chemical Equetion Presentation The purine nucleoside 2,6-diaminopurine- 2′-deoxyriboside is prepared by the direct glycosylation of the 2,6-bis(tetramethylsuccinimide) derivative of the parent purine heterocycle 4 with 2-deoxy-3,5-di-O-(p-toluoyl)-α-D-erythro-pentofuranosyl chloride 5 using the sodium salt method. 2′-Deoxyisoguanosine is prepared from 2,6-diaminopurine by a five-step procedure. The purine heterocycle isoguanine is prepared by selective diazotization of 2,6-diaminopurine and then converted to the N9-trityl derivative to increase solubility. After silylation of the O 2-carbonyl with TMSCl, the N6-amino group is protected as the tetramethylsuccinimide (M4SI). The O2-carbonyl is protected as the DPC derivative, and the trityl group is removed. The resulting product is glycosylated in good yield to generate fully protected 2′-deoxyisoguanosine.

Process for producing 2'-deoxyguanosine

The invention provides a process for producing 2′-deoxyguanosine, characterized in that the process includes reacting one compound selected from the group consisting of guanosine, guanosine 5′-monophosphate, and 2-amino-6-substituted purine with 2′-deoxynucleoside in the presence of nucleoside deoxyribosyl transferase and a hydrolase. According to the process of the present invention, 2′-deoxyguanosine can be synthesized efficiently from inexpensive and easily available starting materials. Since no guanosine, which disturbs purification, is virtually present in a reaction mixture, isolation and purification of 2′-deoxyguanosine can be performed in a very simple manner. Thus, the process for producing 2′-deoxyguanosine is practical.

Enzymatic synthesis of 2'-deoxyguanosine with nucleoside deoxyribosyltransferase-II.

Nucleoside deoxyribosyltransferase-II (NdRT-II) of Lactobacillus helveticus, which catalyzes the transfer of a glycosyl residue from a donor deoxyribonucleoside to an acceptor base, has a broad specificity for the acceptor bases. Six-substituted purines were found to be substrates as acceptor bases for NdRT-II. Using this property of the enzyme, we established a practical procedure for enzymatic synthesis of 2'-deoxyguanosine (dGuo), consisting of the transglycosylation from thymidine to 6-substituted purine (2-amino-6-chloropurine; ACP) instead of natural guanine and the conversion of 2-amino-6-chloropurine-2'-deoxyriboside (ACPdR) to dGuo with bacterial adenosine deaminase. Through the successive reactions, dGuo was synthesized in high yield.

Synthesis of sugar-modified 2,6-diaminopurine and guanine nucleosides from guanosine via transformations of 2-aminoadenosine and enzymatic deamination with adenosine deaminase

Treatment of 2,6-diaminopurine riboside (2-aminoadenosine) with α- acetoxyisobutyryl bromide in acetonitrile gave mixtures of the trans 2',3'- bromohydrin acetates 2. Treatment of 2 with zinc-copper couple effected reductive elimination, and deprotection gave 2,6-diamino-9-(2,3-dideoxy-β- D-erythro-pent-2-enofuranosyl)purine (3a). Treatment of 2 with Dowex 1 x 2 (OH-) resin in methanol gave the 2',3-anhydro derivative 4. Stannyl radical- mediated hydrogenolysis of 2 and deprotection gave the 2'-deoxy 6a and 3'- deoxy 7a nucleosides. Treatment of the 3',5'-O-(tetraisopropyldisiloxanyl) derivative (5a) with trifluoromethanesulfonyl chloride - 4- (dimethylamino)pyridine gave 2'-triflate 5c. Displacement with lithium azide -dimethylformamide and deprotection gave the arabino 2'-azido derivative 8a, which was reduced to give 2,6-diamino-9 (2-amino-2-deoxy-β-D- arabinofuranosyl)purine (8b). Sugar-modified 2,6-diaminopurine nucleosides were treated with adenosine deaminase to give the corresponding guanine analogues. Treatment of 2,6-diaminopurine riboside (2-aminoadenosine) with α-acetoxyisobutyryl bromide in acetonitrile gave mixtures of the trans 2',3'-bromohydrin acetates 2. Treatment of 2 with zinc-copper couple effected reductive elimination, and deprotection gave 2,6-diamino-9-(2,3-dideoxy-β-D-erythro-pent-2-enofuranosyl) purine (3a). Treatment of 2 with Dowex 1 × 2 (OH-) resin in methanol gave the 2',3'-anhydro derivative 4. Stannyl radical-mediated hydrogenolysis of 2 and deprotection gave the 2'-deoxy 6a and 3'-deoxy 7a nucleosides. Treatment of the 3',5'-O-(tetraisopropyldisiloxanyl) derivative (5a) with trifluoromethanesulfonyl chloride - 4-(dimethylamino)pyridine gave 2'-triflate 5c. Displacement with lithium azide - dimethylformamide and deprotection gave the arabino 2'-azido derivative 8a, which was reduced to give 2,6-diamino-9-(2-amino-2-deoxy-β-D-arabinofuranosyl)purine (8b). Sugar-modified 2,6-diaminopurine nucleosides were treated with adenosine deaminase to give the corresponding guanine analogues.