38819-10-2

Basic information

• Product Name: 9-(BETA-D-ARABINOFURANOSYL)GUANINE
• Synonyms: 2-AMino-9-((2R,3S,4S,5R)-3,4-dihydroxy-5-(hydroxyMethyl)tetrahydrofuran-2-yl)-1H-purin-6(9H)-one;9-beta-D-Arabinofuranosylguanine Hydrate;Arabinoguanosine;Araguanosine;ara-Guanosine;Guanine arabinoside;-D-Arabinofuranosylguanine Hydrate;9-&beta
• CAS NO: 38819-10-2
• Molecular Formula: C₁₀H₁₃N₅O₅
• Molecular Weight: 283.24
• Mol File: 38819-10-2.mol

Chemical Properties

• Melting Point: 225°C(lit.)
• Boiling Point: 775.9 °C at 760 mmHg
• Flash Point: 423.1 °C
• Appearance: Slightly off white to white powder
• Density: 2.25 g/cm³
• Vapor Pressure: 2.44E-25mmHg at 25°C
• Refractive Index: 1.955
• Storage Temp.: 2-8°C
• Solubility: DMSO: >10mg/mL
• PKA: 9?+-.0.20(Predicted)
• CAS DataBase Reference: 9-(BETA-D-ARABINOFURANOSYL)GUANINE(CAS DataBase Reference)
• NIST Chemistry Reference: 9-(BETA-D-ARABINOFURANOSYL)GUANINE(38819-10-2)
• EPA Substance Registry System: 9-(BETA-D-ARABINOFURANOSYL)GUANINE(38819-10-2)

Safety Data

• Hazard Codes: Xn
• Statements: 22-36/37/38
• Safety Statements: 26
• WGK Germany: 3
• RTECS: MF8301000
• Hazardous Substances Data: 38819-10-2(Hazardous Substances Data)

Usage

Uses

Used in Anticancer Applications:
9-(BETA-D-ARABINOFURANOSYL)GUANINE is used as an inducer of apoptosis and an inhibitor of DNA synthesis for its antineoplastic properties. It is particularly effective against malignant T-lymphoid cells, where it accumulates and is phosphorylated to produce ara-GTP, which is then incorporated into the DNA. This process leads to a 92% inhibition of DNA replication in CEM cells, a model for human T lymphoblasts, after 30 minutes when used at a concentration of 50 μM. Additionally, Ara-G halts the cell cycle at the sub-G1 phase and induces apoptosis in these cells.
Used in Preclinical Models:
In syngeneic bone marrow containing 6C3HED tumor cells, treatment with ara-G (100 mM) ex vivo prior to transplantation increases the survival of lethally irradiated mice and induces reconstitution of lymphoid, myeloid, and erythroid cell linages.
Used in Pharmaceutical Industry:
9-(BETA-D-ARABINOFURANOSYL)GUANINE is used as an antimetabolite for the development of novel therapeutic agents targeting cancer cells. Its unique mechanism of action and ability to inhibit DNA synthesis make it a valuable compound in the search for new cancer treatments.
Used in Research and Development:
Ara-G is used as a research tool for studying the mechanisms of DNA synthesis inhibition, cell cycle regulation, and apoptosis induction in various cell types, particularly those involved in cancer progression. This knowledge can be applied to develop more targeted and effective cancer therapies.

InChI:InChI=1/C10H13N5O5/c11-10-13-7-4(8(19)14-10)12-2-15(7)9-6(18)5(17)3(1-16)20-9/h2-3,5-6,9,16-18H,1H2,(H3,11,13,14,19)/t3-,5-,6+,9-/m1/s1

Upstream product

• 69304-44-5 3',5'-O-1,1,3,3-tetraisopropyldisiloxan-1,3-diyl-guanosine 
• 3083-77-0 araU 
• 73-40-5 2-amino-6-hydroxypurine 
• 70284-18-3 9-β-D-arabinofuranosyl-2-chlorohypoxanthine 
• 120595-74-6 2-Amino-6-chloro-9-β-D-arabinofuranosylpurine 
• 99691-93-7 8-Carbamoyl-2'-O-p-toluenesulfonyladenosine 
• 148313-05-7 9-<β-D-arabinofuranosyl>-O⁶-<2-(4-nitrophenyl)ethyl>guanine 
• 34079-68-0 2,6-diamino-9-(β-D-arabinofuranosyl)-purine 
• 160549-10-0 2,3,5-tri-O-benzyl-D-arabinofuranose 
• 62255-44-1 1-O-acetyl-2,3,5-tris-O-(benzyl)-α, β-D-arabinofuranose 
• 35085-24-6 2-amino-6-chloro-9-(2,3,5-triphenylmethoxy-β-D-arabinofuranosyl)purine 
• 118-00-3 G 
• 221092-57-5 2'-O-acetyl-3',5'-O-(tetraisopropyldisiloxane-1,3-diyl)-ara-guanosine 
• 142941-91-1 3',5'-O-(1,1,3,3-tetraisopropyldisiloxane-1,3-diyl)-2'-O-[(trifluoromethyl)sulfonyl]-β-D-guanosine 

Downstream Products

• 81475-43-6 9-[2-Hydroxy-1-(2-hydroxy-1-hydroxymethyl-ethoxy)-ethyl]-2-imino-1,2,3,9-tetrahydro-purin-6-one 
• 59981-79-2 9-β-D-Arabinofuranosylguanine 5'-Monophosphate 
• 114378-32-4 7-(benzo<α>pyrene-6-yl)guanine 
• 34973-29-0 8-(benzo<α>pyren-6-yl)guanine 
• 114378-31-3 8-(benzo<α>pyren-6-yl)guanosine 
• 114378-30-2 8-(benzo<α>pyren-6-yl)guanosine 
• 1187-84-4 S-methyl-L-cysteine 
• 2140-65-0 1-methylguanosine 
• 74491-89-7 9-(2',3',5'-tri-O-acetyl-β-D-arabinofuranosyl)guanine 
• 199601-35-9 N-[9-((2R,3S,4S,5R)-3,4-Dihydroxy-5-hydroxymethyl-tetrahydro-furan-2-yl)-6-oxo-6,9-dihydro-1H-purin-2-yl]-isobutyramide 
• 129835-17-2 9-[3',5'-O-(1,1,3,3-tetraisopropyldisiloxane-1,3-diyl)-β-D-arabinofuranosyl]guanine 
• 352522-10-2 2',3',5'-tri-O-acetylguanosine 
• 908371-58-4 N²-acetyl-2'-deoxy-2'-methylselenoguanosine 
• 908371-51-7 N²-acetyl-9-[2'-O-acetyl-3',5'-O-(1,1,3,3-tetraisopropyldisiloxane-1,3-diyl)-β-D-arabinofuranosyl]guanine 

Relevant articles and documents

Synthesis of 2'-iodo- and 2'-bromo-ATP and GTP analogues as potential phasing tools for X-ray crystallography

Ara-adenosine (adenine 9-β-D-arabinofuranoside) and ara-guanosine (guanine 9-β-D-arabinofuranoside) are converted into 2' halogenated ATP and GTP analogues by triflation and subsequent inversion of configuration at C- 2'. For the commercially unavailable ara-guanosine a short synthesis starting from guanosine is presented. The nucleotide analogues could serve for the preparation of heavy atom derivatives of ATP- and GTP-binding proteins useful for protein crystal structure determination by MIR/MAD phasing.

MODIFIED OLIGONUCLEOTIDES AND METHODS OF USE IN TAUOPATHIES

Oligonucleotides comprising modifications at the 2' and/or 3' positions(s) along with methods of 5 making and use against Alzheimer disease and other tauopathies are disclosed.

MODIFIED OLIGONUCLEOTIDES AND METHODS OF USE

Modified oligonucleotides comprising modifications at the 2' and/or 3' positions(s) along with methods of making and use, e.g., against HBV are disclosed.

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.

Use of Citrobacter koseri whole cells for the production of arabinonucleosides: A larger scale approach

Purine arabinosides are well known antiviral and antineoplastic drugs. Since their chemical synthesis is complex, time-consuming, and polluting, enzymatic synthesis provides an advantageous alternative. In this work, we describe the microbial whole cell synthesis of purine arabinosides through nucleoside phosphorylase-catalyzed transglycosylation starting from their pyrimidine precursors. By screening of our microbial collection, Citrobacter koseri (CECT 856) was selected as the best biocatalyst for the proposed biotransformation. In order to enlarge the scale of the transformations to 150 mL for future industrial applications, the biocatalyst immobilization by entrapment techniques and its behavior in different reactor configurations, considering both batch and continuous processes, were analyzed. C. koseri immobilized in agarose could be used up to 68 times and the storage stability was at least 9 months. By this approach, fludarabine (58% yield in 14 h), vidarabine (71% yield in 26 h) and 2,6-diaminopurine arabinoside (77% yield in 24 h), were prepared.

Synthesis of 9-β-d-arabinofuranosylguanine by combined use of two whole cell biocatalysts

Unlike the preparation of other purine nucleosides, transglycosylation from a pyrimidine nucleoside and guanine is difficult because of the low solubility of this base. Thus, another strategy, based on the coupled action of two whole cell biocatalyzed reactions, transglycosylation and deamination, was used. Enterobacter gergoviae and Arthrobacter oxydans were employed to synthesize 9-β-d-arabinofuranosylguanine (AraG), an efficient anti leukemic drug.

Stereoselective synthesis of 9-β-d-arabianofuranosyl guanine and 2-amino-9-(β-d-arabianofuranosyl)purine

9-β-d-Arabianofuranosyl guanine (6) and 2-amino-9-(β-d- arabianofuranosyl)purine (8) were prepared from 2-amino-6-chloro-9-(2,3,5- triphenylmethoxyl-β-d-arabianofuranosyl)purine (4), a key intermediate which was stereoselectively prepared from 2,3,5-triphenylmethoxyl-d- arabianofuranose and 2-amino-6-chloro-purine. The yield of the intermediate was obviously improved and only β-isomer was formed by using the activated molecular sieve as environmental friendly catalyst, overcoming the defect that a 1:1 mixture of α- and β-isomers was formed, which was difficult to separate, when toxic mercury cyanide was previously used as catalyst.

An efficient and scalable synthesis of arabinosylguanine and 2′-deoxy-2′-fluoro-guanosine

An efficient conversion from commercially available 2,6-diaminopurine-2′,3′,5′-tri-O-benzyl arabinoside to arabinosylguanine and its further transformation to 2′-deoxy-2′-fluoro-guanosine is outlined. This process has been used to produce more than one hundred grams of final product. Copyright

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.

Nucleosides. Part LV. Efficient synthesis of arabinoguanosine building blocks

From guanosine (1) as starting molecule, protected arabinoguanosine derivatives such as phosphoramidite precursors and arabinoguanosine (18) itself were prepared in high yields. Inversion of the configuration at C(2') was achieved by introduction of the (trifluoromethyl)sulfonyl residue and subsequent displacement by nucleophiles like acetate, bromide, and azide. The guanine moiety was protected at the amide function by the 2-(4-nitrophenyl)ethyl (npe) group on O6 and at the NH2 function by the 2-(4-nitrophenyl)ethoxycarbonyl (npeoc) group.