Chemical Identity and Structural Features

((2R,3R,4R)-3-(Benzoyloxy)-4-fluoro-4-methyl-5-oxotetrahydrofuran-2-yl)methyl benzoate (Aladdin SKU: R177832) is a chiral, fluorinated γ-lactone. Its tetrahydrofuran-2-one ring carries a quaternary carbon at C-4 bearing both a fluorine atom and a methyl group — a gem-fluoro/methyl motif that confers significant conformational rigidity and metabolic stability relative to unfluorinated analogues. The three contiguous stereocenters at C-2, C-3, and C-4 are all defined in the R configuration, establishing a well-characterized chiral environment essential for enantioselective synthesis.

Two benzoate ester groups serve as protecting groups: one acylates the C-3 hydroxyl directly on the lactone ring, while the other acylates the primary hydroxymethyl group appended at C-2. The benzoate moieties provide both crystallinity (facilitating purification and characterization) and orthogonal deprotection possibilities under basic hydrolysis conditions (e.g., methanolic ammonia or sodium methoxide), allowing selective unveiling of the underlying polyol functionality in downstream synthetic steps.

The combination of a strained lactone electrophile, a gem-fluoromethyl quaternary center, and differentially removable benzoate protections makes this compound a versatile synthon for medicinal chemistry programs targeting nucleoside-like scaffolds.

Synthetic Utility and Applications

Fluorinated nucleoside analogue synthesis: The core γ-fluorolactone scaffold of R177832 closely mimics the furanose ring of ribose and 2-deoxyribose, making it a recognized building block for constructing C-nucleoside and N-nucleoside analogues in which a gem-fluoro/methyl group replaces the natural 4'-hydrogen or hydroxyl. Such structural modifications are well-established strategies for improving resistance to phosphorolytic cleavage and nucleoside-phosphorylase-mediated catabolism, key challenges in antiviral and anticancer nucleoside drug development.

Antiviral research: Quaternary 4'-fluorinated nucleoside analogues have attracted considerable interest as inhibitors of viral RNA-dependent RNA polymerases (RdRps) and reverse transcriptases. R177832 can serve as a chiral lactone precursor from which, following benzoate deprotection and electrophilic or nucleophilic glycosylation steps, a range of purine or pyrimidine base-bearing fluorinated nucleosides may be assembled.

Asymmetric synthesis and methodology: Beyond nucleoside chemistry, the compound represents a useful chiral pool reagent. The (2R,3R,4R) configuration can be transferred to downstream products, avoiding the need for asymmetric catalysis when the target requires this stereochemical arrangement. The activated lactone carbonyl also participates in ring-opening reactions with nitrogen, oxygen, and carbon nucleophiles, enabling access to open-chain fluorinated amino acid or polyol frameworks.

Medicinal chemistry SAR studies: The dual benzoate protection allows researchers to study structure–activity relationships (SAR) at both C-3 and the C-2 hydroxymethyl positions independently, after sequential deprotection, without compromising the stereochemical integrity of the C-4 fluoromethyl quaternary center.

Handling, Storage, and Safety Guidelines

General precautions: As with all fine chemicals of this structural class, R177832 should be handled in accordance with good laboratory practice (GLP). Avoid inhalation of dust or aerosols and contact with skin and eyes. Use appropriate personal protective equipment (PPE): nitrile gloves, safety glasses, and a lab coat. Work in a well-ventilated area or under a fume hood when weighing or dissolving the compound.

Storage: Store the compound in a tightly sealed container under an inert atmosphere (nitrogen or argon) in a cool, dry location away from light. Lactone rings can be susceptible to hydrolysis under humid or basic conditions; accordingly, moisture exclusion during storage is critical for maintaining chemical integrity. Specific storage temperature recommendations should be confirmed from the product data sheet provided with the material (Aladdin SKU R177832).

Solubility and dissolution: Fluorinated lactones of this type are generally soluble in common organic solvents such as dichloromethane (DCM), tetrahydrofuran (THF), ethyl acetate, acetonitrile, and dimethyl sulfoxide (DMSO). Aqueous solubility is expected to be low. Prepare stock solutions under inert conditions and store at appropriate temperatures to prevent hydrolysis of either the lactone or benzoate ester functionalities.

Waste disposal: Dispose of all waste in compliance with local institutional and regulatory guidelines for halogenated organic compounds. Do not pour organic solvent waste down the drain.

Note: Specific physical data (melting point, optical rotation, exact solubility values) should be obtained from the certificate of analysis (CoA) supplied with each lot of R177832. Flag these values for verification before use in publications.

Quality, Purity, and Analytical Characterization

Expected analytical profile: A high-quality lot of R177832 should be characterized by the following routine analyses. Researchers should request and review the certificate of analysis (CoA) for each batch before use.

• Identity (NMR): Proton (¹H) and carbon-13 (¹³C) NMR spectra in deuterated solvents (e.g., CDCl₃) should confirm the regiochemistry and connectivity of the benzoate esters, the lactone carbonyl, and the methyl group. Fluorine-19 (¹⁹F) NMR is particularly informative for confirming the gem-fluorine environment and its coupling pattern with adjacent protons and carbons.
• Stereochemical purity: Optical rotation measurement and/or chiral HPLC analysis should confirm enantiomeric and diastereomeric excess. Given the three contiguous stereocenters, rigorous stereochemical characterization is essential prior to use in asymmetric synthesis.
• Chemical purity (HPLC): Reversed-phase HPLC with UV detection is the standard method for assessing chemical purity. Target purity levels should meet the specification stated on the CoA.
• Mass spectrometry: High-resolution mass spectrometry (HRMS) or LC-MS should confirm the molecular ion consistent with the molecular formula.

Researchers conducting sensitive biological assays or enantioselective syntheses are strongly advised to perform independent analytical verification upon receipt, as batch-to-batch variability can affect downstream results.

Ordering and Technical Support

((2R,3R,4R)-3-(Benzoyloxy)-4-fluoro-4-methyl-5-oxotetrahydrofuran-2-yl)methyl benzoate is available from Aladdin Scientific under catalog number R177832. To place an order or request a quotation, contact your regional Aladdin Scientific representative or visit the Aladdin Scientific website and search by SKU or compound name.

Custom quantities and bulk orders: For projects requiring non-standard quantities, custom purity specifications, or dedicated lot reservation, please contact Aladdin Scientific technical sales. Custom synthesis and scale-up inquiries are welcomed.

Technical inquiries: For questions regarding analytical data, synthetic protocols, or compatibility with specific reaction conditions, the Aladdin Scientific technical support team is available to assist. When submitting an inquiry, please reference SKU R177832 and provide details of the intended application to enable the most relevant guidance.

Documentation: Safety Data Sheets (SDS) and Certificates of Analysis (CoA) for each lot are available upon request and through the Aladdin Scientific online portal. Researchers are encouraged to review the SDS before handling and to retain the CoA for laboratory records and publication supplementary materials.