2239-64-7

Usage

Chemical Properties

solid

InChI:InChI=1/C10H12N4O3S/c15-2-6-5(16)1-7(17-6)14-4-13-8-9(14)11-3-12-10(8)18/h3-7,15-16H,1-2H2,(H,11,12,18)

Upstream product

• 91713-46-1 6-Chloro-9-(2-deoxy-3,5-di-O-p-toluoyl-β-D-erythro-pentofuranosyl)purine 
• 50-44-2 6H-purine-6-thione 
• 87-42-3 6-chloropurine 
• 890-38-0 2-deoxyinosine 
• 50-44-2 6-mercaptopurine 
• 157930-09-1 6-Mercaptopurine 
• 50-89-5 thymidine 
• 951-78-0 2'-deoxyuridine 
• 4330-21-6 2-deoxy-3,5-di-O-p-toluoyl-α-D-erythro-pentofuranosyl chloride 
• 687983-85-3 1-[9-((2R,4S,5R)-4-Acetoxy-5-acetoxymethyl-tetrahydro-furan-2-yl)-9H-purin-6-yl]-pyridinium 
• 145060-59-9 Acetic acid (2R,3S,5R)-2-acetoxymethyl-5-(6-thioxo-1,6-dihydro-purin-9-yl)-tetrahydro-furan-3-yl ester 
• 106568-79-0 9-(3',5'-di-O-acetyl-2'-deoxy-β-D-erythro-pentofuranosyl)-1H-purine-6(9H)-one 

Downstream Products

• 139887-92-6 9-{(2R,4S,5R)-5-[Bis-(4-methoxy-phenyl)-phenyl-methoxymethyl]-4-hydroxy-tetrahydro-furan-2-yl}-1,9-dihydro-purine-6-thione 
• 145060-60-2 (2R,3S,5R)-5-[6-(2,4-Dinitro-phenylsulfanyl)-purin-9-yl]-2-hydroxymethyl-tetrahydro-furan-3-ol 
• 23526-11-6 S-methylthiodeoxyinosine 
• 194918-44-0 3-(9-{(2R,4S,5R)-5-[Bis-(4-methoxy-phenyl)-phenyl-methoxymethyl]-4-hydroxy-tetrahydro-furan-2-yl}-9H-purin-6-ylsulfanyl)-propionitrile 
• 163882-50-6 (2R,3S,5R)-2-[Bis-(4-methoxy-phenyl)-phenyl-methoxymethyl]-5-(6-methylsulfanyl-purin-9-yl)-tetrahydro-furan-3-ol 
• 145060-62-4 (2R,3S,5R)-2-[Bis-(4-methoxy-phenyl)-phenyl-methoxymethyl]-5-[6-(2,4-dinitro-phenylsulfanyl)-purin-9-yl]-tetrahydro-furan-3-ol 
• 145060-61-3 5'-O-(4,4'-dimethoxytriphenylmethyl)-2'-deoxy-6-(2,4-dinitrophenyl)thiopurine-3'-O-(2-cyanoethyl-N,N-diisopropylamino)-phosphoramidite 
• 139887-93-7 2,2-Dimethyl-propionic acid 9-{(2R,4S,5R)-5-[bis-(4-methoxy-phenyl)-phenyl-methoxymethyl]-4-hydroxy-tetrahydro-furan-2-yl}-9H-purin-6-ylsulfanylmethyl ester 
• 139887-94-8 2,2-Dimethyl-propionic acid 9-{(2R,4S,5R)-4-acetoxy-5-[bis-(4-methoxy-phenyl)-phenyl-methoxymethyl]-tetrahydro-furan-2-yl}-9H-purin-6-ylsulfanylmethyl ester 

Relevant academic research and scientific papers

Bio-catalytic synthesis of unnatural nucleosides possessing a large functional group such as a fluorescent molecule by purine nucleoside phosphorylase

Unnatural nucleosides are attracting interest as potential diagnostic tools, medicines, and functional molecules. However, it is difficult to couple unnatural nucleobases to the 1′-position of ribose in high yield and with β-regioselectivity. Purine nucleoside phosphorylase (PNP, EC2.4.2.1) is a metabolic enzyme that catalyses the conversion of inosine to ribose-1α-phosphate and free hypoxanthine in phosphate buffer with 100% α-selectivity. We explored whether PNP can be used to synthesize unnatural nucleosides. PNP catalysed the reaction of thymidine as a ribose donor with purine to produce 2′-deoxynebularine (3, β form) in high conversion (80%). It also catalysed the phosphorolysis of thymidine and introduced a pyrimidine base with a halogen atom substituted at the 5-position into the 1′-position of ribose in moderate yield (52-73%), suggesting that it exhibits loose selectivity. For a bulky purine substrate [e.g., 6-(N,N-di-propylamino)], the yield was lower, but addition of a polar solvent such as dimethyl sulfoxide (DMSO) increased the yield to 74%. PNP also catalysed the reaction between thymidine and uracil possessing a large functional fluorescent group, 5-(coumarin-7-oxyhex-5-yn) uracil (C4U). Conversion to 2′-deoxy-[5-(coumarin-7-oxyhex-5-yn)] uridine (dRC4U) was drastically enhanced by DMSO addition. Docking simulations between dRC4U and E. coli PNP (PDB 3UT6) showed the uracil moiety in the active-site pocket of PNP with the fluorescent moiety at the entrance of the pocket. Thus, the bulky fluorescent moiety has little influence on the coupling reaction. In summary, we have developed an efficient method for producing unnatural nucleosides, including purine derivatives and modified uracil, using PNP.

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.

Purine nucleoside synthesis from uridine using immobilised Enterobacter gergoviae CECT 875 whole cells

Biocatalysed purine nucleoside synthesis was carried out using immobilised Enterobacter gergoviae CECT 875. Similar yields (80-95%) in adenosine were obtained with both free and immobilised cells though in the last case a long reaction time was necessary. The immobilised cells can be reused at least for more than 30 times without significant loss of enzymatic activity. The immobilised biocatalyst in agarose is active in the synthesis of unnatural nucleosides.

Post-synthetic introduction of labile functionalities onto purine residues via 6-methylthiopurines in oligodeoxyribonucleotides

Two methods are described for the preparation of oligodeoxynucleotides containing 6-methylthiopurine residues. 6-Methylthiopurine phosphoramidite (6) has been prepared and incorporated into oligomers. Methylation with methyl iodide of 6-thiopurine (or 6-thioguanine) in oligomers also exclusively produces oligomers containing 6-methylthiopurine (or 6-methylthioguanine). The methylthio group at defined purine residues in the deprotected oligomers can be oxidized selectively and converted at the final step into various functional groups including radioactive 35S-thio group, a useful tag for cross-linking studies.

Preparation of oligodeoxynucleotides containing 6-methylthiopurine residues by chemical synthesis or specific methylation

Two methods (chemical synthesis and specific methylation) are described for the preparation of oligodeoxynucleotides containing 6-methylthiopurine residues. 6-Methylthiopurine phosphoramidite (6) is prepared and incorporated into oligomers. Methylation with methyl iodide of 6-thiopurine (or 6-thioguanine) in oligonucleotides also leads to exclusive production of 6-methylthiopurine (or 6-methylthioguanine) oligomers.

Synthesis and duplex stability of oligodeoxynucleotides containing 6-mercaptopurine

simple procedures for conversion of 2′-deoxyinosine into 6-thio-2′-deoxyinosine (III) and for preparation of S-protected 6-mercatopurine phosphoramidite (VI) are described. The monomer (VI) was incorporated into DNA oligomers and converted into oligomers containing 6-mercaptopurine and other purines modified at the 6-position. Measurements of the melting temperature (Tm) of DNA duplexes containing 6-mercaptopurine or 6-thioguanine show that both preferentially pair with cystosine rather than with thymine, but that the presence of the S generally destabilises the DNA duplex.

A convenient synthesis of 2'-deoxy-6-thioguanosine, ara-guanine, ara-6-thioguanine and certain related purine nucleosides by the stereospecific sodium salt glycosylation procedure [1]

A simple and high-yield synthesis of biologically significant 2'-deoxy-6-thioguanosine, ara-6-thioguanine and araG has been accomplished employing the stereospecific sodium salt glycosylation method. Glycosylation of the sodium salt of 6-chloro- and 2-amino-6-chloropurine (1 and 2, respectively) with 1-chloro-2-deoxy-3,5-di-O-(p-toluoyl)-α-D-erythro-pentofuranose gave the corresponding N-9 substituted nucleosides as major products with the β-anomeric configuration (4 and 5, respectively) along with a minor amount of the N-7 positional isomers (6 and 7). Treatment of 4 with hydrogen sulfide in methanol containing sodium methoxide gave 2'-deoxy-6-thioinosine in 93% yield. Similarly, 5 was transformed into 2'-deoxy-6-thioguanosine (β-TGdR, 11) in 71% yield. Reaction of the sodium salt of 2 with 1-chloro-2,3,5-tri-O-benzyl-α-D-arabinofuranose gave N-7 and N-9 glycosylated products 13 and 9, respectively. Debenzylation of 9 with boron trichloride at -78° gave the versatile intermediate 2-amino-6-chloro-9-β-D-arabinofuranosylpurine 62% yield. Direct treatment of 14 with sodium hydrosulfide furnished ara-6-thioguanine. Alkaline hydrolysis of 14 readily gave 9-β-D-arabinofuranosylguanine (araG, 17), which on subsequent phosphorylation with phosphorus oxychloride in trimethyl phosphate afforded araG 5'-monophosphate.