307306-06-5

Upstream product

• 2265-92-1 1,4-difluoro-2-iodobenzene 
• 21740-23-8 3,5-O-bis(4-chlorobenzoyl)-2-deoxy-α-D-ribofuranosyl chloride 
• 307306-05-4 2,5-difluoro-1-[1-[2-deoxy-3,5-di-O-(p-chlorobenzoyl)-α-D-ribofuranosyl]]benzene 
• 399-94-0 2-bromo-1,4-difluorobenzene 
• 540-36-3 para-difluorobenzene 
• 122-01-0 4-chloro-benzoyl chloride 

Downstream Products

• 307306-15-6 C₂₅H₁₇Cl₂F₂NO₇ 

Relevant academic research and scientific papers

Synthesis of 1-(2-deoxy-β-D-ribofuranosyl)-2,4-difluoro-5- substituted-benzene thymidine mimics, some related α-anomers, and their evaluation as antiviral and anticancer agents

A group of unnatural 1-(2-deoxy-β-D-ribofuranosyl)-2.4-difluorobenzenes having a variety of C-5 substituents (H, Me, F, Cl, Br, I, CF3, CN, NO2, NH2), designed as thymidine mimics, were synthesized for evaluation as anticancer and antiviral agents. The coupling reaction of 3,5-bis-O-(p-chlorobenzoyl) 2-deoxy-α-D-ribofuranosyl chloride with an organocadmium reagent [(2,4-difluorophenyl)2Cd] afforded a mixture of the α- and β-anomeric products (α:β = 3:1 to 10:1 ratio). Treatment of the α-anomer with BF3·Et2O in nitroethane at 110-120°C for 30 min was developed as an efficient method for epimerization of the major α-anomer to the desired β-anomer. The 5-substituted (H, Me, Cl, I, NH2) β-anomers exhibited negligible cytotoxicity in a MTT assay (CC50 = 10-3-10-4 M range), relative to thymidine (CC50 = 10-3-10-5 M range), against a variety of cancer cell lines. In contrast, the 5-NO2 derivative was more cytotoxic (CC50 = 10-5-10-6 M range). A number of 5-substituted β-anomers, and some related α-anomers, that were evaluated using a wide variety of antiviral assay systems [HSV-1, HSV-2, varicella-zoster virus (VZV), vaccinia virus, vesicular stomatitis, cytomegalovirus (CMV) and human immunodeficiency (HIV-1, HIV-2) viruses], showed that this class of unnatural C-aryl nucleoside mimics are inactive antiviral agents.

Syntheses of 4-[1-(2-deoxy-β-D-ribofuranosyl)]-derivatives of 2-substituted-5-fluoroaniline: 'Cytosine replacement' analogs of deoxycytidine for evaluation as anticancer and antihuman immunodeficiency virus (anti-HIV) agents

A group of 4-[1-(2-deoxy-β-D-ribofuranosyl)]-derivatives of 5-fluoroaniline possessing a variety of aryl C-2 substituents (6a R = H, 6b R = F, 6c R = Me) were synthesized. Accordingly, a Heck-type coupling reaction of the 4-iodoaniline derivatives (13a-c) with the bis(tert-butyldimethylsilyl)glycal (11) in the presence of Pd(OAc)2 and Ph3As, followed by removal of the tert-butyldimethylsilyl protection groups using n-Bu4N+F-, yielded the corresponding 4-(β-D-glycero-pentofuran-3-ulos-1-yl)aniline derivatives (14a-c) having a C-3 C=O in the sugar ring. Reduction of the C-3 C=O compounds (14a-c) using NaB(OAc)3H afforded the target 4-[1-(2-deoxy-β-D-ribofuranosyl)]-derivatives of the respective 2-substituted-5-fluoroaniline (6a-c). The deoxycytidine mimic, 3-fluoro-4-[1-(2-deoxy-β-D-ribofuranosyl)]aniline (6a), in which the cytosine ring of deoxycytidine is replaced by a 4-(3-fluoroaniline) ring system, was inactive as an anticancer agent against a variety of tumor cell lines, and as an antihuman immunodeficiency virus (HIV-1, HIV-2) agent. The failure of this unnatural deoxycytidine mimic (6a) to exhibit anticancer-antiviral activity may be due to its inability to undergo phosphorylation by host cell- and virus-induced kinases.