N-Acetyl-5'-O-[bis(4-methoxyphenyl)phenylmethyl]-2'-O-[(1,1-dimethylethyl)dimethylsilyl]cytidine
[CAS# 121058-85-3]

Identification

• Classification: Biochemical >> Nucleoside drugs >> Nucleotides and their analogues
• Name: N-Acetyl-5'-O-[bis(4-methoxyphenyl)phenylmethyl]-2'-O-[(1,1-dimethylethyl)dimethylsilyl]cytidine
• Synonyms: N-[1-[(2R,3R,4R,5R)-5-[[bis(4-methoxyphenyl)-phenylmethoxy]methyl]-3-[tert-butyl(dimethyl)silyl]oxy-4-hydroxyoxolan-2-yl]-2-oxopyrimidin-4-yl]acetamide
• Molecular Formula: C₃₈H₄₇N₃O₈Si
• Molecular Weight: 701.88
• CAS Registry Number: 121058-85-3
• SMILES: CC(=O)NC1=NC(=O)N(C=C1)[C@H]2[C@@H]([C@@H]([C@H](O2)COC(C3=CC=CC=C3)(C4=CC=C(C=C4)OC)C5=CC=C(C=C5)OC)O)O[Si](C)(C)C(C)(C)C

Properties

• Solubility: Insoluble (7.7E^-5 g/L) (25 °C), Calc.^*
• Density: 1.19±0.1 g/cm³ (20 °C 760 Torr), Calc.^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software V11.02 (©1994-2015 ACD/Labs)

Safety Data

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

Discovery and Applications

N-Acetyl-5'-O-[bis(4-methoxyphenyl)phenylmethyl]-2'-O-[(1,1-dimethylethyl)dimethylsilyl]cytidine is a chemically modified nucleoside designed to enhance stability and utility in nucleic acid research and therapeutics. The compound features a unique combination of protecting groups and modifications that improve its performance in a variety of biochemical applications.

The development of N-Acetyl-5'-O-[bis(4-methoxyphenyl)phenylmethyl]-2'-O-[(1,1-dimethylethyl)dimethylsilyl]cytidine is part of an ongoing quest to create more stable and functional nucleosides. Researchers focus on adding protecting groups to nucleosides to enhance their resistance to chemical and enzymatic degradation, ensuring they remain intact during complex biochemical processes. The acetyl group at the N-position, the bis(4-methoxyphenyl)benzyl (DMT) group at the 5' position, and the tert-butyldimethylsilyl (TBDMS) group at the 2' position were all designed to achieve this goal.

N-acetyl-5'-O-[bis(4-methoxyphenyl)benzyl]-2'-O-[(1,1-dimethylethyl)dimethylsilyl]cytidine incorporates several protecting groups: the N-acetyl group enhances chemical stability; the DMT group protects the 5' hydroxyl during oligonucleotide synthesis, facilitating precise assembly; and the TBDMS group protects the 2' hydroxyl, increasing resistance to nucleases and ensuring stability during chemical reactions.

Protecting groups on this modified nucleoside prevent degradation and unwanted side reactions during oligonucleotide synthesis and other biochemical processes. The DMT group ensures selective deprotection, allowing for stepwise addition of nucleotides during synthesis. The TBDMS group provides stability by preventing nuclease activity at the 2' hydroxyl position, while the N-acetyl group adds further chemical stability to the nucleoside.

This modified nucleoside is essential in the automated synthesis of oligonucleotides. Protecting groups ensure accurate and efficient construction of DNA and RNA sequences, which is important for a variety of research and therapeutic applications.

N-acetyl-5'-O-[bis(4-methoxyphenyl)phenylmethyl]-2'-O-[(1,1-dimethylethyl)dimethylsilyl]cytidine is used to develop stable RNA therapeutics such as siRNA and antisense oligonucleotides. These modifications enhance resistance to enzymatic degradation, thereby improving the stability and efficacy of the therapeutic molecule in vivo.

In molecular biology, this compound aids in the study of RNA structure and function. Its enhanced stability allows researchers to more effectively study RNA interactions and mechanisms, thereby advancing the understanding of genetic regulation and RNA-based technologies.

Protecting groups can significantly increase the resistance of nucleosides to chemical and enzymatic degradation. The DMT and TBDMS groups facilitate the precise and efficient synthesis of oligonucleotides. Such compounds can be used in both research and therapeutic settings, particularly in RNA-based drug development.

The chemical synthesis of such modified nucleosides can be complex and costly. While modifications can improve stability, they can also affect the biological activity and delivery of RNA therapeutics, thus requiring careful optimization in therapeutic applications.

References

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