beta-D-Ribofuranose 1-acetate 2,3,5-tribenzoate (often abbreviated as 1-O-acetyl-2,3,5-tri-O-benzoyl-β-D-ribofuranose) is a key protected ribose derivative used almost exclusively as a crucial synthetic intermediate in organic chemistry, particularly in the synthesis of nucleosides, nucleotides, and their analogs. Its applications stem from its specific protecting group pattern:
Nucleoside Synthesis (Primary Application):
Antiviral Drugs: e.g., Remdesivir, Sofosbuvir analogs, Ribavirin analogs.
Anticancer Agents: e.g., Gemcitabine analogs, cladribine.
Antibiotics: e.g., Puromycin, Cordycepin analogs.
mRNA Vaccine Components: Modified nucleosides like N1-methylpseudouridine (though synthesis paths vary, protected ribose intermediates like this are often involved).
Fluorescent Nucleotides: For probes and diagnostics.
Locked Nucleic Acids (LNAs): As a starting point for modification.
Glycosyl Donor: The anomeric acetate (C1-OAc) is a good leaving group under mild Lewis acid catalysis (e.g., SnCl₄, TMSOTf, BF₃·Et₂O).
Stereoselectivity: The neighboring 2-O-benzoate group participates in the reaction, directing the incoming nucleobase (e.g., silylated purine or pyrimidine) to attack from the β-face (from the top). This results in high stereoselectivity for the formation of β-nucleosides, which are the naturally occurring configuration.
Protection: The benzoate groups (at C2, C3, C5) protect the hydroxyl groups during the glycosylation reaction and subsequent steps. Benzoates are stable under glycosylation conditions and can be removed later (e.g., with ammonia/methanol) without affecting the glycosidic bond.
Examples: This intermediate is fundamental in synthesizing natural ribonucleosides (like adenosine, guanosine, cytidine, uridine) and critically important modified nucleosides used in:
Oligonucleotide Synthesis (Less Direct):
While not used directly in solid-phase oligonucleotide synthesis (which typically uses phosphoramidites), this protected ribose is a vital precursor.
It can be converted into protected ribonucleoside phosphoramidite building blocks. After glycosylation to form the protected nucleoside, the 5'-OH benzoate is selectively removed (often using mild base like hydrazine or ammonia in methanol under controlled conditions), and the 5'-OH is then phosphitylated to form the phosphoramidite monomer used in automated RNA synthesis.
Synthesis of Modified Sugars and Glycoconjugates:
The protected ribose scaffold can be further chemically modified before glycosylation or after nucleoside formation (following selective deprotection). Modifications might include fluorination, methylation, or other substitutions at specific carbon positions to create sugar-modified nucleoside analogs.
It can serve as a starting point for synthesizing other complex carbohydrates or glycoconjugates where a protected ribose moiety is required, although this is less common than its use in nucleoside synthesis.
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