2140-79-6

Basic information

• Product Name: 2'-O-Methyladenosine
• Synonyms: AMI;2'-O-Methyladdenosine;(2R,3R,4R,5R)-5-(6-AMino-9H-purin-9-yl)-2-(hydroxyMethyl)-4-Methoxytetrahydrofuran-3-ol;2'-O-METHYLADENOSINE;2'-O-Methyl-D-adenosine;5-(6-aminopurin-9-yl)-2-(hydroxymethyl)-4-methoxyoxolan-3-ol;2'-OMe-A;(2R,3R,4R,5R)-5-(6-aminopurin-9-yl)-2-(hydroxymethyl)-4-methoxyoxolan-3-ol
• CAS NO: 2140-79-6
• Molecular Formula: C₁₁H₁₅N₅O₄
• Molecular Weight: 281.27
• EINECS: 1308068-626-2
• Product Categories: Bases & Related Reagents;Carbohydrates & Derivatives;Heterocycles;Nucleotides;Biochemicals and Reagents;Nucleoside Analogs;Nucleosides, Nucleotides, Oligonucleotides
• Mol File: 2140-79-6.mol
• Article Data: 22

Chemical Properties

• Melting Point: 200-202 C
• Boiling Point: 623.759 °C at 760 mmHg
• Flash Point: 331.038 °C
• Appearance: White to Off-white/Powder
• Density: 1.843 g/cm³
• Storage Temp.: −20°C
• Solubility: DMSO (Slightly), Methanol (Slightly, Heated, Sonicated), Water (Slightly)
• PKA: 13.13±0.70(Predicted)
• Water Solubility: Soluble in water.
• CAS DataBase Reference: 2'-O-Methyladenosine(CAS DataBase Reference)
• NIST Chemistry Reference: 2'-O-Methyladenosine(2140-79-6)
• EPA Substance Registry System: 2'-O-Methyladenosine(2140-79-6)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26-36-24/25
• WGK Germany: 3
• Hazardous Substances Data: 2140-79-6(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
2'-O-Methyladenosine is used as an adenosine analog for preparing nucleoside derivatives, which act as inhibitors of RNA-dependent RNA viral polymerase. This application is crucial in the development of antiviral drugs targeting specific viral enzymes, thereby offering potential treatments for viral infections.
Used in Biochemical Research:
As a nucleoside modification, 2'-O-Methyladenosine is utilized in biochemical research to study the effects of methyl group addition on the 2' hydroxyl of the ribose moiety of adenosine. This research can provide insights into the structure-function relationships of nucleosides and their role in various biological processes, including the development of novel therapeutic agents.

Preparation

preparation of 2′-O-MethyladenosineMethylation of adenosine with methyl iodide in anhydrous alkaline mediumAdenosine is treated with CH3I in an anhydrous alkaline medium at 0°C for 4 h. The major products of this reaction are monomethylated adenosine at either the 2′-O or 3′-O position (total of 64%) and the side products are dimethylated adenosine (2′,3′-O-dimethyladenosi, 21%, and N6-2′-O-dimethyladenosine, 11%). The ratio of 2′-O- and 3′-O-methyladenosine has been found to be 8 to 1. Therefore, this reaction preferentially favors the synthesis of 2′-O-methyladenosine. The monomethylated adenosine is isolated from reaction mixture by a silica gel column chromatography. Then the pure 2′-O-methyladenosine can be separated by crystallization in ethanol from the mixture of 2′-O and 3′-O-methylated isomers. The overall yield of 2′-O-methyladenosine is 42%.https://doi.org/10.1016/0304-4165(80)90276-7

Biological Activity

2'-O-Methyladenosine, a methylated adenine residue is found in urine of normals as well as in urine of adenosine deaminase (ADA) deficient patients. 2'-O-Methyladenosine exhibits unique hypotensive activities.

Upstream product

• 186581-53-3 diazomethane 
• 58-61-7 adenosine 
• 512-56-1 trimethyl phosphite 
• 17287-03-5 trimethylsulphonium hydroxide 
• 1899-02-1 trimethylphenylammonium hydroxide 
• 74230-06-1 trimethylselenonium hydroxyde 
• 18107-18-1 diazomethyl-trimethyl-silane 
• 110-71-4 1,2-dimethoxyethane 
• 57817-83-1 N⁶,O^2'-methyladenosine 
• 684-93-5 1-methyl-1-nitrosourea 
• 80-48-8 methyl p-toluene sulfonate 
• 647834-80-8 O-levulinyl acetonoxime 
• 10300-22-8 3'-O-methyladenosine 
• 244184-56-3 3',5'-di-O-acetyl-2'-O-methyl-6-chloro-2-aminopurine riboside 

Downstream Products

• 1000003-68-8 C₃₉H₃₁N₅O₈ 
• 110764-72-2 N⁶-benzoyl-5'-(4,4'-dimethoxytrityl)-O^2'-methyladenosine 

Relevant articles and documents

Naturally occurring 2'-O-methylpurine nucleosides with hypotensive properties

2'-O-Methylinosine (1) has been isolated for the first time and shown to be an intrinsic hypotensive principle. Its probable in vivo precursor. 2'-O-methyladenosine (3), showed stronger and even orally potent hypotensive activity. Resistance of the methyladenosine (3) against adenosine deaminase is thought to contribute to its long-lasting activity. The effect of both nucleosides (1 and 3) was not accompanied with any significant change in heart rate, which is often observed with adenosine.

Identification of Flavin Mononucleotide as a Cell-Active Artificial N6-Methyladenosine RNA Demethylase

N6-Methyladenosine (m6A) represents a common and highly dynamic modification in eukaryotic RNA that affects various cellular pathways. Natural dioxygenases such as FTO and ALKBH5 are enzymes that demethylate m6A residues in mRNA. Herein, the first identification of a small-molecule modulator that functions as an artificial m6A demethylase is reported. Flavin mononucleotide (FMN), the metabolite produced by riboflavin kinase, mediates substantial photochemical demethylation of m6A residues of RNA in live cells. This study provides a new perspective to the understanding of demethylation of m6A residues in mRNA and sheds light on the development of powerful small molecules as RNA demethylases and new probes for use in RNA biology.

Selective inhibition of TRPM2 channel by two novel synthesized ADPR analogues

Transient receptor potential melastatin-2 (TRPM2) channel critical for monitoring internal body temperature is implicated in the pathological processes such as neurodegeneration. However, lacking selective and potent TRPM2 inhibitors impedes investigation and validation of the channel as a drug target. To discover novel and selective TRPM2 inhibitors, a series of adenosine 5′-diphosphoribose analogues were synthesized, and their activities and selectivity were evaluated. Whole-cell patch-clamp recordings were employed for screen and evaluation of synthesized compounds. Two compounds, 7i and 8a, were identified as TRPM2 inhibitors with IC50 of 5.7 and 5.4?μm, respectively. Both 7i and 8a inhibited TRPM2 current without affecting TRPM7, TRPM8, TRPV1 and TRPV3. These two TRPM2 inhibitors can serve as new pharmacological tools for further investigation and validation of TRPM2 channel as a drug target, and the summarized structure–activity relationship (SAR) may also provide insights into further improving existing inhibitors as potential lead compounds.

Noncanonical RNA Nucleosides as Molecular Fossils of an Early Earth—Generation by Prebiotic Methylations and Carbamoylations

The RNA-world hypothesis assumes that life on Earth started with small RNA molecules that catalyzed their own formation. Vital to this hypothesis is the need for prebiotic routes towards RNA. Contemporary RNA, however, is not only constructed from the four canonical nucleobases (A, C, G, and U), it also contains many chemically modified (noncanonical) bases. A still open question is whether these noncanonical bases were formed in parallel to the canonical bases (chemical origin) or later, when life demanded higher functional diversity (biological origin). Here we show that isocyanates in combination with sodium nitrite establish methylating and carbamoylating reactivity compatible with early Earth conditions. These reactions lead to the formation of methylated and amino acid modified nucleosides that are still extant. Our data provide a plausible scenario for the chemical origin of certain noncanonical bases, which suggests that they are fossils of an early Earth.

Improved synthesis and isolation of 2'-O-methyladenosine: Effective and scalable enzymatic separation of 2'/3'-O-methyladenosine regioisomers

An efficient separation of a mixture of 2'/3'-O-methyladenosine regioisomers (1 + 2: 1:1) has been developed by selective enzymatic acylation using immobilized Pseudomonas cepacia lipase (PSL-C) in combination with acetonoxime levulinate as acyl donor. Th

Antiviral amphipathic oligo- and polyribonucleotides: Analogue development and biological studies

A series of novel N1 alkylated purine nucleic acids were polymerized either enzymatically or by automated synthesis to further establish the SAR requirements for HIV, RT, and HCMV activity. Out of the series, two constructs, 2′-O-methyl-1-allylinosinic ac

Novel fluoride-labile nucleobase-protecting groups for the synthesis of 3'(2')-O-aminoacylated RNA sequences

With the aim to develop a general approach to a total synthesis of aminoacylated t-RNAs and analogues, we describe the synthesis of stabilized, aminoacylated RNA fragments, which, upon ligation, could lead to aminoacylated t-RNA structures. Novel RNA phosphoramidites with fluoride-labile 2'-O-[(triisopropylsilyl)-oxy]methyl (=tom) sugar-protecting and N-{{2-[(triisopropylsilyl)oxy]benzyl}oxy}carbonyl (=tboc) base-protecting groups were prepared (Schemes 4 and 5), as well as a solid support containing an immobilized N6-tboc-protected adenosine with an orthogonal (photolabile) 2'-O-[(S)-1-(2-nitrophenyl)ethoxy]methyl (=(S)-npeom) group (Scheme 6). From these building blocks, a hexameric oligoribonucleotide was prepared by automated synthesis under standard conditions (Scheme 7). After the detachment from the solid support, the resulting fully protected sequence 34 was aminoacylated with L-phenylalanine derivatives carrying photolabile N-protecting groups (→42 and 43; Scheme 9). Upon removal of the fluoride-labile sugar- and nucleobase-protecting groups, the still stabilized, partially with the photolabile group protected precursors 44 and 45, respectively, of an aminoacylated RNA sequence were obtained (Scheme 9 and Fig. 3). Photolysis of 45 under mild conditions resulted in the efficient formation of the 3'(2')-O-aminoacylated RNA sequence 46 (Fig. 4). Additionally, we carried out model investigations concerning the stability of ester bonds of aminoacylated ribonucleotide derivatives under acidic conditions (Table) and established conditions for the purification and handling of 3'(2')-O-aminoacylated RNA sequences and their stabilized precursors.

Improved synthetic approaches toward 2'-O-methyl-adenosine and guanosine and their N-acyl derivatives

We developed several improved approaches toward 2'-O-methyl adenosine and guanosine and their N-acyl derivatives. (a) Transglycosylation of N4- acetyl-5', 3'-di-O-acetyl-2'-O-methyl cytidine with N6-Bz-adenine provided N6-benzoyl-5'3'-di-O-acetyl-2'-O-methyl adenosine in 50% yield. (b) Regioselective methylation of 2-amino-6-chloro purine riboside with MeI/NaH followed by hydrolysis provided 2'-O-Me-guanosine in high yield. The same 2'- O-Me-precursor was transformed into 2'-O-Me-adenosine in 58% yield. (c) Very efficient transformation of 2,6-diamino-purine riboside into N2-isobutyryl (isopropylphenoxyacetyl) 2'-O-Me-guanosine through methylation of 5',3'-O- TIPDSi derivative followed by selective N2-acylation, deamination and desylilation provided target compounds in 70% combined yield. (d) Mg2+ and Ag+ directed methylation of N1-Bzl-guanosine proceeded in >80% yield with ratio of 2'-O-Me-3'-O-Me=9:1. The same methylation of adenosine with Ag+ and Sr2+ acetylacetonates provided 2'-O-Me-adenosine in 75-80% yield. (C) 2000 Elsevier Science Ltd.

Antisense inhibition of ras gene with chimeric and alternating oligonucleotides

Compositions and methods are provided for the modulation of expression of the human ras gene in both the normal and activated forms. Oligonucleotides are provided that have methylene(methylimino) linkages alternating with phosphorothioate or phosphodiester linkages. Further oligonucleotides are provide that have a first region having a methylene(methylimino) linkage alternating with a phosphorothioate or phosphodiester linkage and a second region having phosphorothioate linkages. Such oligonucleotides can be used for diagnostics as well as for research purposes including methods for diagnosis, detection and treatment of conditions arising from the activation of the H-ras gene.

Chemical syntheses of 2'-O-methoxy purine nucleosides

Several processes for the chemical synthesis of 2'-O-methoxy purine nucleosides are herein disclosed.