The α ‐ L ‐Threofuranosyl‐(3′→2′)‐oligonucleotide System (‘TNA'): Synthesis and Pairing Properties

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 µM.

Section: Introductionmentioning

confidence: 99%

Synthesis of Novel 2'-Spirocyclopropanoid 4'-Deoxythreosyl Phosphonic Acid Nucleoside Analogues

Shen¹,

Hong

2013

“…Of these compounds, threose nucleosides, 2 such as, PMDTA (1) and PMDTT (2), have been previously synthesized ( Figure 1) because they can be assembled from natural precursors. 3 Furthermore, it has been demonstrated that threose nucleic acids (TNA) form duplexes with DNA and RNA that are thermally stable, in an analogous manner to natural nucleic acid association. The triphosphates of threose nucleosides are substrates of several polymerases, and can be enzymatically incorporated into DNA.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Conformation of Novel 3'-Branched Threosyl-5'-Deoxyphosphonic Acid Nucleoside Analogues

Shen¹,

Kang²,

Kim³

et al. 2012

The discovery that threosyl phosphonate nucleoside (PMDTA, EC 50 = 2.53 µM) 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 µM).

“…Threose phosphonate nucleosides 6 such as PMDTA (1) and PMDTT (2) have been synthesized (Figure 1) because they can be assembled from natural precursor molecules. 7 It has been demonstrated that threose nucleic acids (TNA) form duplex with DNA and RNA of thermal stability, similar to that of the natural nucleic acid association. The phosphonoalkoxy group of the proposed threose nucleoside phosphonates is bound at the 3'-position, bring the phosphorus atom and the nucleobase closer to each other than in previously synthesized nucleoside phosphonates where the phosphonate group is bound to the primary hydroxyl group of the nucleoside.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Conformation of Novel 4'-Fluorinated 5'-Deoxythreosyl Phosphonic Acid Nucleosides as Antiviral Agents

Kang¹,

Kim²,

Choi³

et al. 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 α-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 µM.