N-Benzoyl-5'-O-[bis(4-methoxyphenyl)phenylmethyl]-2'-O-methyladenosine
[CAS# 110764-72-2]

Identification

• Classification: Biochemical >> Nucleoside drugs >> Nucleoside intermediate
• Name: N-Benzoyl-5'-O-[bis(4-methoxyphenyl)phenylmethyl]-2'-O-methyladenosine
• Synonyms: N-[9-[(2R,3R,4R,5R)-5-[[bis(4-methoxyphenyl)-phenylmethoxy]methyl]-4-hydroxy-3-methoxyoxolan-2-yl]purin-6-yl]benzamide
• Molecular Formula: C₃₉H₃₇N₅O₇
• Molecular Weight: 687.74
• CAS Registry Number: 110764-72-2
• SMILES: CO[C@@H]1[C@@H]([C@H](O[C@H]1N2C=NC3=C(N=CN=C32)NC(=O)C4=CC=CC=C4)COC(C5=CC=CC=C5)(C6=CC=C(C=C6)OC)C7=CC=C(C=C7)OC)O

Properties

• Solubility: Insoluble (2.7E^-6 g/L) (25 °C), Calc.^*
• Density: 1.32±0.1 g/cm³ (20 °C 760 Torr), Calc.^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software V11.02 (©1994-2016 ACD/Labs)

Safety Data

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

Discovery and Applications

N-Benzoyl-5'-O-[bis(4-methoxyphenyl)benzyl]-2'-O-methyladenosine is a chemically modified nucleoside designed to enhance nucleic acid stability and functionality. The compound has three notable modifications: a benzoyl group at the N position, a bis(4-methoxyphenyl)benzyl (DMT) group at the 5' position, and a methyl group at the 2' position of the ribose sugar. These modifications make it a valuable tool for nucleic acid synthesis and applications in research and therapy.

The discovery of N-Benzoyl-5'-O-[bis(4-methoxyphenyl)benzyl]-2'-O-methyladenosine stems from efforts to improve the chemical and enzymatic stability of nucleosides. The introduction of protecting groups such as DMT facilitates selective reactions at specific positions, which is essential for the stepwise assembly of oligonucleotides. The 2'-O-methyl modification enhances resistance to enzymatic degradation, while the benzoyl group adds another layer of protection and specificity. These combined modifications make nucleosides more stable and more suitable for a variety of applications.

The protective DMT group at the 5' position prevents unwanted reactions during oligonucleotide synthesis, allowing for precise construction of nucleic acid sequences. The 2'-O-methyl group enhances nucleoside stability by protecting it from ribonucleases, an enzyme that degrades RNA. The benzoyl group further increases stability and may affect the binding affinity and specificity of the nucleoside in biological systems.

N-Benzoyl-5'-O-[bis(4-methoxyphenyl)benzyl]-2'-O-methyladenosine is primarily used in the automated synthesis of oligonucleotides. The DMT group is selectively removed during synthesis to ensure the correct assembly of the nucleic acid sequence. This is essential for creating DNA and RNA molecules for research and therapeutic purposes.

The 2'-O-methyl modification increases the stability and longevity of RNA therapeutics. This modification is particularly beneficial for small interfering RNAs (siRNAs) and antisense oligonucleotides that regulate gene expression. The enhanced stability means that these therapeutic molecules can remain active longer, thereby increasing their efficacy.

In molecular biology, this modified nucleoside is used to study the structure and function of RNA. Its stability allows researchers to more accurately study RNA interactions and mechanisms, thereby advancing the understanding of genetic regulation and the development of RNA-based technologies.

The main advantages of N-benzoyl-5'-O-[bis(4-methoxyphenyl)benzyl]-2'-O-methyladenosine are its enhanced stability and functionality. The DMT group ensures accurate oligonucleotide synthesis, the 2'-O-methyl group enhances resistance to degradation, and the benzoyl group further increases stability. These properties make it indispensable in both research and therapeutic settings.

Despite the benefits of this compound, there are challenges in using it. The synthesis of modified nucleosides is complex and costly. In addition, while the 2'-O-methyl modification improves stability, it can also affect the bioactivity and delivery of RNA therapeutics, requiring careful design and optimization in therapeutic applications.

References

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