2',3',5'-Tri-O-acetyl-D-adenosine
[CAS# 7387-57-7]

Identification

• Classification: Biochemical >> Nucleoside drugs >> Nucleoside intermediate
• Name: 2',3',5'-Tri-O-acetyl-D-adenosine
• Synonyms: [(2R,3R,4R,5R)-3,4-diacetyloxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methyl acetate
• Molecular Formula: C₁₆H₁₉N₅O₇
• Molecular Weight: 393.35
• CAS Registry Number: 7387-57-7
• SMILES: CC(=O)OC[C@@H]1[C@H]([C@H]([C@@H](O1)N2C=NC3=C(N=CN=C32)N)OC(=O)C)OC(=O)C

Properties

• Density: 1.6±0.1 g/cm³, Calc.^*
• Melting point: 174-175 °C(Expl.)
• Index of Refraction: 1.68, Calc.^*
• Boiling Point: 594.1±60.0 °C (760 mmHg), Calc.^*
• Flash Point: 313.1±32.9 °C, Calc.^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Safety Data

• Hazard Symbols: GHS07 Warning
• Risk Statements: H302-H315-H319-H335
• Safety Statements: P261-P305+P351+P338

Discovery and Applications

2',3',5'-Tri-O-acetyl-D-adenosine is a peracetylated derivative of adenosine, a purine nucleoside that plays a central role in cellular metabolism and biochemical processes. The chemical modification of adenosine by acetylation at the hydroxyl groups of the ribose moiety enhances its lipophilicity and affects its biochemical properties, making it useful in synthetic chemistry and pharmacological applications. The compound is known for its utility in nucleoside chemistry, particularly in the synthesis of modified nucleotides and nucleic acid analogs.

The discovery and characterization of 2',3',5'-Tri-O-acetyl-D-adenosine were driven by efforts to modify naturally occurring nucleosides to improve their chemical stability and enhance their utility in biochemical research. The acetylation of adenosine has been well-documented in the literature, with early studies focusing on the protection of hydroxyl groups to facilitate selective modifications at other positions in the nucleoside structure. The compound has been widely employed in organic synthesis, particularly as an intermediate in the preparation of nucleoside analogs that serve as potential antiviral and anticancer agents.

One of the significant applications of 2',3',5'-Tri-O-acetyl-D-adenosine is its role in protecting the hydroxyl groups of adenosine during glycosylation reactions. By acetylating the ribose hydroxyls, chemists can prevent unwanted side reactions, allowing for regioselective modifications at the nucleobase or the anomeric center. This approach has been widely used in the synthesis of nucleoside analogs for medicinal chemistry, including the development of prodrugs that rely on enzymatic deacetylation in vivo to release the active nucleoside.

In pharmaceutical research, peracetylated nucleosides such as 2',3',5'-Tri-O-acetyl-D-adenosine have been investigated as prodrug candidates. The increased lipophilicity of acetylated nucleosides facilitates cellular uptake, improving bioavailability in drug formulations. Once inside the cell, enzymatic hydrolysis removes the acetyl groups, releasing the parent nucleoside for metabolic incorporation. This strategy has been explored for various nucleoside-based antiviral and anticancer drugs, where selective activation in target cells enhances therapeutic efficacy while reducing systemic toxicity.

Another important application of 2',3',5'-Tri-O-acetyl-D-adenosine is in nucleic acid chemistry, particularly in the chemical synthesis of oligonucleotides and RNA analogs. The compound serves as a precursor in phosphoramidite chemistry, where selective deprotection strategies enable controlled polymerization of nucleotides. This approach has been instrumental in the development of synthetic RNA molecules for research and therapeutic applications, including antisense oligonucleotides and RNA interference technologies.

In biochemical studies, 2',3',5'-Tri-O-acetyl-D-adenosine has been utilized in enzymatic investigations to probe the activity of nucleoside hydrolases and esterases. By studying the enzymatic hydrolysis of the acetyl groups, researchers have gained insights into the specificity and kinetics of enzymes involved in nucleoside metabolism. Such studies contribute to the understanding of nucleoside processing in biological systems and inform the design of enzyme inhibitors for therapeutic applications.

The use of 2',3',5'-Tri-O-acetyl-D-adenosine extends to carbohydrate chemistry, where it has been employed in glycosylation reactions to prepare glycosylated nucleosides and related derivatives. These modified nucleosides have found applications in glycobiology, vaccine development, and the synthesis of biologically active compounds. The controlled introduction of sugar moieties onto nucleosides provides a valuable approach for tuning the biological activity and pharmacokinetic properties of nucleoside-based drugs.

Research into the synthetic applications of 2',3',5'-Tri-O-acetyl-D-adenosine continues to expand, with new methodologies being developed for its efficient preparation and functionalization. Advances in catalytic and enzymatic approaches have improved the selectivity and yield of acetylation reactions, facilitating the large-scale production of peracetylated nucleosides for industrial and pharmaceutical applications. Additionally, the compound remains a key intermediate in the design of novel nucleoside analogs for emerging therapeutic areas, including antiviral drug development and nucleic acid-based therapies.

The well-established role of 2',3',5'-Tri-O-acetyl-D-adenosine in nucleoside chemistry and pharmaceutical research underscores its importance as a versatile chemical intermediate. Its applications in protecting group strategies, prodrug development, oligonucleotide synthesis, and enzymatic studies highlight its broad utility across multiple scientific disciplines.

References

2018. Chemoenzymatic synthesis of cytokinins from nucleosides: ribose as a blocking group. Organic & Biomolecular Chemistry, 16(12).
DOI: 10.1039/C8OB00223A

2016. Computer-simulation-based selection of optimal monomer for imprinting of tri-O-acetyl adenosine in a polymer matrix: calculations for benzene solution. Journal of Molecular Modeling, 22(7).
DOI: 10.1007/s00894-016-3030-0

2021. Efficient access to 3′-O-phosphoramidite derivatives of tRNA related N6-threonylcarbamoyladenosine (t6A) and 2-methylthio-N6-threonylcarbamoyladenosine (ms2t6A). RSC Advances, 11(5).
DOI: 10.1039/D0RA09803E