1-((2S,3R,4S,5S)-3-Fluoro-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-5-methylpyrimidine-2,4(1H,3H)-dione

Base Information

• Chemical Name: 1-((2S,3R,4S,5S)-3-Fluoro-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-5-methylpyrimidine-2,4(1H,3H)-dione
• CAS No.: 163252-36-6
• Molecular Formula: C₁₀H₁₃FN₂O₅
• Molecular Weight: 260.222
• Hs Code.: 2934999090
• UNII: IN51MVP5F1
• DSSTox Substance ID: DTXSID2057659
• Nikkaji Number: J945.904I
• Wikipedia: Clevudine
• Wikidata: Q1100864
• NCI Thesaurus Code: C95210
• Metabolomics Workbench ID: 149897
• ChEMBL ID: CHEMBL458875
• Mol file: 163252-36-6.mol

Synonyms:1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)-5-methyl-2,4(1H,3H)-pyrimidinedione,;1-(2-deoxy-2-fluoro-beta-L-arabinofuranosyl)-5-methyl-2,4(1H,3H)-pyrimidinedione;1-(2-fluoro-2-deoxy-beta-arabinofuranosyl)thymine;1-(2-fluoro-2-deoxy-beta-D-arabinofuranosyl)thymine;1-(2-fluoro-5-methyl-beta,L-arabinofuranosyl)uracil;1-(2-fluoro-beta-L-arabinofuranosyl)thymine;2'-deoxy-2'-fluoroarabinofuranosylthymine;2'-fluoro-5-methyl-1-beta-D-arabinofuranosyluracil;2'-fluoro-5-methylarabinosyluracil;2'-fluoro-5-methylarabinosyluracil, 2-(14)C-labeled;5-methyl-2'-fluoroarauracil;Clevudine;D-FMAU;FMAU;L-FMAU

Chemical Property of 1-((2S,3R,4S,5S)-3-Fluoro-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-5-methylpyrimidine-2,4(1H,3H)-dione

Chemical Property:

• Melting Point: 184-185°
• Refractive Index: 1.592
• PKA: 9.55±0.10(Predicted)
• PSA: 104.55000
• Density: 1.559 g/cm³
• LogP: -1.56630
• Storage Temp.: under inert gas (nitrogen or Argon) at 2-8°C
• Solubility.: DMSO (Slightly), Methanol (Slightly)
• XLogP3: -0.9
• Hydrogen Bond Donor Count: 3
• Hydrogen Bond Acceptor Count: 6
• Rotatable Bond Count: 2
• Exact Mass: 260.08084968
• Heavy Atom Count: 18
• Complexity: 413

Purity/Quality:

99% ^*data from raw suppliers

Clevudine ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: CC1=CN(C(=O)NC1=O)C2C(C(C(O2)CO)O)F
• Isomeric SMILES: CC1=CN(C(=O)NC1=O)[C@@H]2[C@@H]([C@H]([C@@H](O2)CO)O)F
• Recent ClinicalTrials: ANRS HB 05 Multicenter Study Evaluating Efficacy and Safety of Clevudine Monotherapy Versus Tenofovir Monotherapy Versus Combination Therapy of Clevudine and Tenofovir for 96 Weeks in HBeAg Negative Patients With Chronic Hepatitis B, na?ve to Anti-VHB Therapy
• Recent EU Clinical Trials: A randomized, double blind, multicenter study evaluating efficacy and safety of Clevudine monotherapy versus Tenofovir monotherapy versus combination therapy of Clevudine and Tenofovir for 96 weeks in HBeAg negative patients with chronic hepatitis B, na?ve to anti-VHB therapy
• Description: Clevudine is a fluorinated b-L-nucleoside analog launched for the oral treatment of chronic HBV infection. It is the fifth nucleoside or nucleotide analog to be marketed for this indication. The previous drugs from this class include lamivudine, adefovir, entecavir, and telbivudine. In HBV-expressing human hepatoma cell line 2.2.15, clevudine inhibits HBV DNA synthesis with an EC50 of 0.1 μM, and does not show cytotoxicity up to 200 μM. It is phosphorylated by cellular kinases to the active triphosphate derivative, which subsequently inhibits HBV DNA polymerase and HBV replication. 466 Shridhar Hegde and Michelle Schmidt Clevudine-5′-triphosphate has an intracellular half-life of 16.5 h. Interestingly, it is a non-competitive inhibitor of viral polymerase, and inhibits HBV replication without being incorporated into the DNA. The pharmacokinetic profile of clevudine was linear with a plasma half-life of approximately 60 h. Clevudine was undetectable in plasma after 4 weeks following the cessation of dosing.The most common adverse events reported with clevudine treatment include infection, asthenia, dyspepsia, abdominal pain, headache, and diarrhea.Clevudine is chemically derived from L-ribose by first incorporating acyl protective groups to produce 1-O-acetyl-2,3,5-tri-O-benzoyl-b-L-ribofuranose intermediate, which is then converted to 1,3,5-tri-O-benzoyl-a-L-ribofuranose in two steps by treating To Market, To Market 2007 467 with hydrogen chloride and subsequent hydrolysis and acyl migration. The remaining steps leading to clevudine include conversion of the C2-hydroxy group to C2-fluoro group with triethylamine trihydrofluoride, formation of the corresponding ribofuranosyl bromide intermediate with hydrogen bromide and acetic acid, condensation with silylated thymine, and removal of benzoyl protective groups with methanolic ammonia.
• Uses: Antiviral drug, used for the treatment of Hepatitis B.

Technology Process of 1-((2S,3R,4S,5S)-3-Fluoro-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-5-methylpyrimidine-2,4(1H,3H)-dione

There total 90 articles about 1-((2S,3R,4S,5S)-3-Fluoro-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-5-methylpyrimidine-2,4(1H,3H)-dione which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 100.0%

1-(3',5'-di-O-benzoyl-2'-deoxy-2'-fluoro-β-D-arabinofuranosyl)thymine (97614-47-6) → 1-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)thymine (69256-17-3,163252-36-6,2923-73-1)

Guidance literature:

With sodium methylate; In methanol; at 20 ℃; for 2h;

DOI:10.1021/acs.orglett.6b03626

Reference yield: 100.0%

1-(2-deoxy-2-fluoro-3,5-di-O-benzoyl-α-D-arabinofuranosyl)thymine (97614-48-7) → 1-(2-deoxy-2-fluoro-α-D-arabinofuranosyl)thymine (97672-34-9,163252-36-6,2923-73-1)

Guidance literature:

With sodium methylate; In tetrahydrofuran; methanol; at 20 ℃; for 2h;

DOI:10.1021/acs.orglett.6b03626

Reference yield: 93.4%

1-(3',5'-di-O-benzoyl-2'-deoxy-2'-fluoro-β-L-arabinofuranosyl)thymine (171721-03-2) → clevudine (163252-36-6,2923-73-1)

Guidance literature:

With sodium methylate; In methanol; at 20 ℃; for 2h; pH=9 - 10; Green chemistry;

upstream raw materials:

1-[(2R,3R,4R,5R)-3-Fluoro-4-(tetrahydro-pyran-2-yloxy)-5-(tetrahydro-pyran-2-yloxymethyl)-tetrahydro-furan-2-yl]-5-methyl-1H-pyrimidine-2,4-dione

O-2,2'-cyclo-5-methyluridine

1-(3,5-O-di(tetrahydropyran-2-yl)-β-D-arabinofuranosyl)thymine

5-Methyluridine

Downstream raw materials:

C₂₉H₃₉FN₂O₁₂S

L(-)FMAUTP

5'-O-(4,4'-dimethoxytrityl)-2'-fluoro-2'-deoxy-5-methyluridine

C₁₀H₁₁FN₂O₆

Refernces

• 1、 Garcia, Javier,Diaz-Rodriguez, Alba,Fernandez, Susana,Sanghvi, Yogesh S.,Ferrero, Miguel,Gotor, Vicente. "New concept for the separation of an anomeric mixture of α/β-D-nucleosides through regioselective enzymatic acylation or hydrolysis processes". . p. 9765 - 9771. Retrieved 2006.
• 2、 -. "S-ANTIGEN TRANSPORT INHIBITING OLIGONUCLEOTIDE POLYMERS AND METHODS". Paragraph 0056; 0334. . Retrieved 2021/06/22.
• 3、 -. "MODIFIED OLIGOMERIC COMPOUNDS AND USES THEREOF". Page/Page column 95. . Retrieved 2020/05/15.