• Bulletin of the Korean Chemical Society
• /
• v.33 no.12
• /
• pp.4007-4014
• /
• 2012

Efficient synthetic route to novel 4'-fluorinated 5'-deoxythreosyl phosphonic acid nucleosides was described from glyceraldehyde using Horner-Emmons reaction in the presence of triethyl ${\alpha}$-fluorophosphonoacetate. Glycosylation reaction of nucleosidic bases with glycosly donor 14 gave the nucleosides which were further phosphonated and hydrolyzed to reach desired nucleoside analogues. Synthesized nucleoside analogues 18, 21, 25 and 28 were tested for anti-HIV activity as well as cytotoxicity. Adenine derivatives 18 and 21 showed significant anti-HIV activity up to $100{\mu}M$.

• Bulletin of the Korean Chemical Society
• /
• v.34 no.3
• /
• pp.868-874
• /
• 2013

Efficient synthetic route to novel 2'-spirocyclopropanoid 4'-deoxythreosyl phosphonic acid nucleosides was described from 1,4-dihydroxy-2-butene. Cyclopropane moiety was prepared via ester enolate alkylation using (2-chloroethyl)dimethylsulfonium iodide. Synthesized nucleoside analogues 16, 19, 23 and 26 were tested for anti-HIV activity as well as cytotoxicity. However, none of them showed any anti-HIV activity or cytotoxicity up to 100 ${\mu}M$.

• Archives of Pharmacal Research
• /
• v.28 no.7
• /
• pp.745-749
• /
• 2005

A simple synthetic route for the synthesis of novel methyl branched cyclopropyl phosphonic acid nucleosides is described. The characteristic cyclopropyl moiety 8 was constructed by employing Simmons-Smith reaction as a key step. The condensation of mesylate 11 with natural nucleosidic bases (A,C,T,U) under standard nucleophilic substitution conditions ($K_2CO_3$, 18-Crown-6, DMF) and after subsequent hydrolysis resulted in the formation of target nucleosides, 16, 17, 18, and 19. In addition, the antiviral evaluations of the synthesized nucleotides against various viruses were also performed.

• Bulletin of the Korean Chemical Society
• /
• v.35 no.9
• /
• pp.2743-2748
• /
• 2014

Novel 4'-trifluoromethyl-5'-norcarbocyclic purine phosphonic acid analogs were efficiently synthesized from commercially available 1,3-dihydroxy cyclopentane (5). Trifluoromethylation was successfully performed by using the Ruppert-Prakash reaction. The purine nucleosidic bases were efficiently coupled by using the Mitsunobu reaction. The synthesized adenosine phosphonic acids analogs 13 and 16 were screened for antiviral activity against human immunodeficiency virus-1 (HIV-1). Adenine derivative 13 exhibited significant anti-HIV-1 activity.

• Bulletin of the Korean Chemical Society
• /
• v.31 no.11
• /
• pp.3348-3352
• /
• 2010

Novel 4'-ethyl-5'-norcarbocyclic adenosine phosphonic acid analogues were synthesized from propionaldehyde 5 through a de novo acyclic synthetic route using reiterative Grignard additions and ring-closing metathesis (RCM) as key reactions. The synthesized nucleoside phosphonic acids analogues 17, 18, 19, and 21 were subjected to antiviral screening against human immunodeficiency virus.

• Bulletin of the Korean Chemical Society
• /
• v.32 no.2
• /
• pp.411-416
• /
• 2011

Steric and electronic parameters of 4'-substituents play significant roles in steering the conformation of nucleoside analogues. In order to investigate the relationship of 4'-group with antiviral enhancement, novel 4'-hydroxymethyl-5'-norcarbocyclic adenosine phosphonic acid analogues were designed and synthesized from 2,2-dimethyl-1,3-dioxolane-4-ethanol (5) using reiterative Grignard addition and ring-closing metathesis (RCM) as key reactions. The synthesized adenosine phosphonic acids analogues (22) and (23) were subjected to antiviral screening against HIV-1. Compound (23) exhibited moderate anti-HIV activity ($EC_50$ = 8.61 ${\mu}M$) in the CEM cell line.

• Bulletin of the Korean Chemical Society
• /
• v.33 no.8
• /
• pp.2574-2580
• /
• 2012

The discovery that threosyl phosphonate nucleoside (PMDTA, $EC_{50}=2.53{\mu}M$) is a potent anti-HIV agent has led to the synthesis and biological evaluation of 5'-deoxy versions of threosyl phosphonate nucleosides. In the present study, (E)-3'-phosphonoalkenyl and 3'-phosphonoalkyl nucleoside analogues 13, 16, 20 and 23 were synthesized from acetol and tested for anti-HIV activity and cytotoxicity. The adenine analogue 16 was found to exhibit moderate in vitro anti-HIV-1 activity ($EC_{50}=22.2{\mu}M$).