2'-O-tert-Butyldimethylsilyl-5'-O-(4,4'-dimethoxytrityl)uridine
[CAS# 81246-80-2]

Identification

• Classification: Biochemical >> Nucleoside drugs >> Deoxynucleotides and their analogues
• Name: 2'-O-tert-Butyldimethylsilyl-5'-O-(4,4'-dimethoxytrityl)uridine
• Synonyms: 1-[(2R,3R,4R,5R)-5-[[bis(4-methoxyphenyl)-phenylmethoxy]methyl]-3-[tert-butyl(dimethyl)silyl]oxy-4-hydroxyoxolan-2-yl]pyrimidine-2,4-dione
• Molecular Formula: C₃₆H₄₄N₂O₈Si
• Molecular Weight: 660.83
• CAS Registry Number: 81246-80-2
• SMILES: CC(C)(C)[Si](C)(C)O[C@@H]1[C@@H]([C@H](O[C@H]1N2C=CC(=O)NC2=O)COC(C3=CC=CC=C3)(C4=CC=C(C=C4)OC)C5=CC=C(C=C5)OC)O

Properties

• Solubility: Insoluble (3.5E^-5 g/L) (25 °C), Calc.^*
• Density: 1.24±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

2'-O-tert-butyldimethylsilyl-5'-O-(4,4'-dimethoxytrityl)uridine is a chemically modified nucleoside. It is of great importance in the field of nucleic acid research, especially in the synthesis of oligonucleotides for therapeutic and diagnostic purposes. The modification involves the protection of the 2'-hydroxyl group of uridine with tert-butyldimethylsilyl (TBDMS) and the 5'-hydroxyl group with 4,4'-dimethoxytrityl (DMT).

The development of protected nucleosides such as 2'-O-tert-butyldimethylsilyl-5'-O-(4,4'-dimethoxytrityl)uridine stems from the need for efficient strategies to synthesize RNA and DNA oligonucleotides. The introduction of protecting groups such as TBDMS and DMT allows for the selective deprotection and elongation of nucleotide chains. This approach was pioneered in the 1980s as part of advances in solid phase synthesis of oligonucleotides.

The chemical structure of 2'-O-tert-butyldimethylsilyl-5'-O-(4,4'-dimethoxytrityl)uridine includes a uridine base with the 2'-hydroxyl protected by a TBDMS group. This silyl ether is stable under alkaline conditions but can be selectively removed using fluoride ions. The 5'-hydroxyl is protected by a DMT group, which is acid labile and can be selectively removed in the presence of weak acids.

The main application of this modified nucleoside is in the automated synthesis of RNA and DNA oligonucleotides. The protecting groups facilitate the stepwise elongation of the nucleotide chain while preventing undesirable side reactions.

This modified nucleoside is essential for the development of antisense oligonucleotides, small interfering RNA (siRNA), and other nucleic acid-based therapeutics. These therapeutics are used to target specific mRNA sequences, resulting in gene silencing or modulation.

This modified nucleoside is also used to synthesize probes for the detection of specific nucleic acid sequences. These probes are essential in various diagnostic techniques, including PCR, microarrays, and in situ hybridization.

References

2013. Catalyst recognition of cis-1,2-diols enables site-selective functionalization of complex molecules. Nature Chemistry, 5(8).
DOI: 10.1038/nchem.1726