98983-40-5

Basic information

• Product Name: 9-(2-Deoxy-2-fluoro-beta-D-arabinofuranosyl)-1,9-dihydro-6H-purin-6-one
• Synonyms: 6H-Purin-6-one, 9-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)-1,9-dihydro-;9-(2-Deoxy-2-fluoro-beta-D-arabinofuranosyl)-1,9-dihydro-6H-purin-6-one;9-(2-deoxy-2-fluoro-D-arabinofuranosyl)hypoxanthin;9-(2-deoxy-2-fluoro-D-arabinofuranosyl)hypoxanthine
• CAS NO: 98983-40-5
• Molecular Formula: C10H11FN4O4
• Molecular Weight: 270.219
• Mol File: 98983-40-5.mol
• Article Data: 3

Chemical Properties

• Boiling Point: 744.8 °C at 760 mmHg
• Flash Point: 404.24 °C
• Appearance: /
• Density: 2.01
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.81
• CAS DataBase Reference: 9-(2-Deoxy-2-fluoro-beta-D-arabinofuranosyl)-1,9-dihydro-6H-purin-6-one(CAS DataBase Reference)
• NIST Chemistry Reference: 9-(2-Deoxy-2-fluoro-beta-D-arabinofuranosyl)-1,9-dihydro-6H-purin-6-one(98983-40-5)
• EPA Substance Registry System: 9-(2-Deoxy-2-fluoro-beta-D-arabinofuranosyl)-1,9-dihydro-6H-purin-6-one(98983-40-5)

Safety Data

• Hazardous Substances Data: 98983-40-5(Hazardous Substances Data)

Usage

General Description

9-(2-Deoxy-2-fluoro-beta-D-arabinofuranosyl)-1,9-dihydro-6H-purin-6-one, also known as F-ara-A or Fludarabine, is a synthetic, purine nucleoside analog and an antineoplastic agent. It is used extensively in treatments for hematological malignancies such as chronic lymphocytic leukemia (CLL) and non-Hodgkin's lymphoma. The chemical works by interfering with DNA synthesis, thereby stopping the growth of cancer cells. It is activated by deoxycytidine kinase and is then converted into its active form fludarabine triphosphate, which leads to cell death. Despite its effectiveness, adverse side effects like bone marrow suppression, and neurological complications limit its usage. 9-(2-Deoxy-2-fluoro-beta-D-arabinofuranosyl)-1,9-dihydro-6H-purin-6-one is generally administered through injection or intravenous infusion.

InChI:InChI=1/C10H11FN4O4/c11-5-7(17)4(1-16)19-10(5)15-3-14-6-8(15)12-2-13-9(6)18/h2-5,7,10,16-17H,1H2,(H,12,13,18)/t4-,5+,7-,10-/m1/s1

Upstream product

• 20187-82-0 9-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)adenine 
• 136852-40-9 9-(2-Deoxy-2-fluoro-3,5-di-O-trityl-β-D-arabinofuranosyl)-1-benzylinosine 
• 56632-81-6 1,3-di-O-acetyl-5-O-benzoyl-2-deoxy-2-fluoro-D-arabinofuranosyl bromide 
• 109303-87-9 9-(3-O-acetyl-5-O-benzoyl-2-deoxy-2-fluoro-β-D-arabinofuranosyl)-N⁶-benzoyladenine 
• 4005-49-6 N-benzoyladenine 
• 68-94-0 hypoxanthine 

Relevant articles and documents

The chemoenzymatic synthesis of clofarabine and related 2′-deoxyfluoroarabinosyl nucleosides: The electronic and stereochemical factors determining substrate recognition by E. coli nucleoside phosphorylases

Two approaches to the synthesis of 2-chloro-9-(2-deoxy-2-fluoro-β-D- arabinofuranosyl)adenine (1, clofarabine) were studied. The first approach consists in the chemical synthesis of 2-deoxy-2-fluoro-α-D- arabinofuranose-1-phosphate (12a, 2FAra-1P) via three step conversion of 1,3,5-tri-O-benzoyl-2-deoxy-2-fluoro-α-D-arabinofuranose (9) into the phosphate 12a without isolation of intermediary products. Condensation of 12a with 2-chloroadenine catalyzed by the recombinant E. coli purine nucleoside phosphorylase (PNP) resulted in the formation of clofarabine in 67% yield. The reaction was also studied with a number of purine bases (2-aminoadenine and hypoxanthine), their analogues (5-aza-7-deazaguanine and 8-aza-7- deazahypoxanthine) and thymine. The results were compared with those of a similar reaction with α-D-arabinofuranose-1-phosphate (13a, Ara-1P). Differences of the reactivity of various substrates were analyzed by ab initio calculations in terms of the electronic structure (natural purines vs analogues) and stereochemical features (2FAra-1P vs Ara-1P) of the studied compounds to determine the substrate recognition by E. coli nucleoside phosphorylases. The second approach starts with the cascade one-pot enzymatic transformation of 2-deoxy-2-fluoro-D-arabinose into the phosphate 12a, followed by its condensation with 2-chloroadenine thereby affording clofarabine in ca. 48% yield in 24 h. The following recombinant E. coli enzymes catalyze the sequential conversion of 2-deoxy-2-fluoro-D-arabinose into the phosphate 12a: ribokinase (2-deoxy-2-fluoro-D-arabinofuranose-5-phosphate), phosphopentomutase (PPN; no 1,6-diphosphates of D-hexoses as co-factors required) (12a), and finally PNP. The substrate activities of D-arabinose, D-ribose and D-xylose in the similar cascade syntheses of the relevant 2-chloroadenine nucleosides were studied and compared with the activities of 2-deoxy-2-fluoro-D-arabinose. As expected, D-ribose exhibited the best substrate activity [90% yield of 2-chloroadenosine (8) in 30 min], D-arabinose reached an equilibrium at a concentration of ca. 1:1 of a starting base and the formed 2-chloro-9-(β-D- arabinofuranosyl) adenine (6) in 45 min, the formation of 2-chloro-9-(β-D- xylofuranosyl)adenine (7) proceeded very slowly attaining ca. 8% yield in 48 h.

Nucleosides. CXXXV. Synthesis of some 9-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)-9H-purines and their biological activities

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