2'-Deoxy-5-[3-[(trifluoroacetyl)amino]-1-propynyl]cytidine
[CAS# 115899-38-2]

Identification

• Classification: Pharmaceutical intermediate >> Heterocyclic compound intermediate >> Pyrimidine compound
• Name: 2'-Deoxy-5-[3-[(trifluoroacetyl)amino]-1-propynyl]cytidine
• Synonyms: N-[3-[4-amino-1-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-2-oxopyrimidin-5-yl]prop-2-ynyl]-2,2,2-trifluoroacetamide
• Molecular Formula: C₁₄H₁₅F₃N₄O₅
• Molecular Weight: 376.29
• CAS Registry Number: 115899-38-2
• SMILES: C1[C@@H]([C@H](O[C@H]1N2C=C(C(=NC2=O)N)C#CCNC(=O)C(F)(F)F)CO)O

Properties

• Solubility: Very slightly soluble (0.2 g/L) (25 °C), Calc.^*
• Density: 1.65±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

2'-Deoxy-5-[3-[(trifluoroacetyl)amino]-1-propynyl]cytidine is a chemically modified nucleoside analog derived from 2'-deoxycytidine. The modification at the 5-position of the cytidine base involves the introduction of a propynyl group substituted with a trifluoroacetyl-protected amino moiety. This structural modification confers unique chemical and biological properties compared to the natural nucleoside.

The compound was developed to explore the effects of introducing trifluoroacetyl-protected amino groups into nucleosides, which can influence molecular recognition, binding affinity, and enzymatic stability. Trifluoroacetyl protection is commonly used in organic synthesis to temporarily mask amino functionalities, improving compound stability during chemical reactions and facilitating further functionalization.

Applications of 2'-Deoxy-5-[3-[(trifluoroacetyl)amino]-1-propynyl]cytidine are primarily in nucleic acid research and medicinal chemistry. This nucleoside analog can be incorporated into oligonucleotides through chemical synthesis, enabling studies of nucleic acid structure, hybridization, and interactions. The propynyl group at the 5-position has been shown in similar analogs to increase the thermal stability of DNA duplexes, improving binding specificity and affinity, which is advantageous in antisense and diagnostic probes.

In drug discovery and development, such modified nucleosides are investigated for their potential as antiviral or anticancer agents. Modifications at the nucleobase often alter the interaction of nucleoside analogs with cellular enzymes like DNA polymerases and kinases, potentially leading to selective inhibition of viral replication or cancer cell proliferation. The presence of the trifluoroacetyl group may enhance the molecule’s membrane permeability or metabolic stability, factors critical for pharmacokinetics.

The chemical synthesis of 2'-Deoxy-5-[3-[(trifluoroacetyl)amino]-1-propynyl]cytidine typically involves multi-step reactions starting from natural 2'-deoxycytidine. The propynyl moiety is introduced through Sonogashira-type coupling reactions, followed by protection of the amino group with trifluoroacetyl to prevent side reactions. This synthetic route allows for precise control over substitution patterns and yields compounds suitable for incorporation into oligonucleotides or further chemical modification.

Due to its modified structure, this nucleoside analog is useful in studies requiring enhanced stability or specificity of nucleic acid probes. It also serves as a model compound to investigate the influence of trifluoroacetyl-protected amino groups on nucleoside behavior in biological systems. Such studies contribute to the design of novel nucleoside-based therapeutics and molecular tools.

Overall, 2'-Deoxy-5-[3-[(trifluoroacetyl)amino]-1-propynyl]cytidine represents a class of chemically tailored nucleosides with applications in biochemical research and drug development, offering improved properties for nucleic acid manipulation and potential therapeutic benefits.

References

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