Synthetic routes to 4′-hydroxymethylnucleosides

Youssefyeh, R. D.; Tegg, Derek; Verheyden, Julien P. H.; Jones, Gordon H.; Moffatt, J. G.

doi:10.1016/s0040-4039(01)92658-9

Cited by 22 publications

(10 citation statements)

References 11 publications

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“…4′-Substituted nucleosides have been under development since JG Moffatt's group accomplished the synthesis of 4′-C-fluoro-5′-O-sulphamoyladenosine, the antibiotic nucleocidin and related nucleosides (Verheyden et al, 1975, Jenkins et al, 1976, Owen et al, 1976, Youssefyeh et al, 1977, Jones et al, 1979.…”

Section: Synthesis and Anti-hiv Activity Of 4′-snsmentioning

confidence: 99%

Potential of 4′-C-Substituted Nucleosides for the Treatment of HIV-1

Hayakawa

Kohgo

Kitano

et al. 2004

Antivir Chem Chemother

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Extensive efforts have been made to identify nucleoside reverse transcriptase inhibitors (NRTIs). Eight NRTIs have now been approved for clinical use; however, variants of HIV-1 resistant to these antiviral agents have emerged in patients even when they are treated with combinations [highly active antiretroviral therapy (HAART)]. Thus, the development of novel compounds that are active against drug-resistant HIV-1 variants and that prevent or delay the emergence of resistant HIV-1 variants is urgently needed. Previously, 4'-C-substituted nucleosides (4'-SNs) were designed as new types of NRTIs. They were synthesized and examined as potential therapeutic agents against HIV infection. Among them, several 4'-substituted-2'-deoxynucleosides (4'-SdNs), especially those that bear an ethynyl group, were shown to be active against various laboratory and clinical HIV-1 strains including known drug-resistant variants. These results were recently reported by our collaborators. In this review, we summarize the design, synthesis and demonstrations of the anti-HIV activity of 4'-SNs, and then consider 4'-SNs as potential therapeutic agents for HIV-1.

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Section: Synthesis and Anti-hiv Activity Of 4′-snsmentioning

confidence: 99%

Potential of 4′-C-Substituted Nucleosides for the Treatment of HIV-1

Hayakawa

Kohgo

Kitano

et al. 2004

Antivir Chem Chemother

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“…After evaporation of the reaction mixture, the 5,6-glycol is oxidatively cleaved by periodate, giving the 5-aldehydo derivative after a simple work-up procedure. Finally, the aldehyde is condensed with formaldehyde followed by in situ crossed Cannizzaro reaction with excess formaldehyde, giving the desired 4-C-hydroxymethyl derivative S.5 (Youssefyeh et al, 1977(Youssefyeh et al, , 1979 in 82% yield (3 steps) after crystallization from hexanes.…”

Section: Synthesis Of the Universal Glycosyl Donor S7mentioning

confidence: 99%

“…The key steps in the synthesis of LNA nucleosides are the introduction of the 4‐ C ‐hydroxymethyl functionality followed by selective derivatization of the resulting two diastereotopic hydroxymethyl groups. 4′‐ C ‐Hydroxymethyl nucleosides have been synthesized using both linear (Youssefyeh et al, ; Jones et al, ) and convergent (Leland and Kotick, ; Youssefyeh et al, , ) strategies based on aldol condensation of 5(′)‐aldehydes with formaldehyde followed by a Cannizzaro reaction or sodium borohydride reduction. LNA nucleosides were previously synthesized following linear (Obika et al, ; Koshkin et al, ) as well as convergent (Singh et al, ; Koshkin et al, ,b) strategies.…”

Section: Commentarymentioning

confidence: 99%

Locked Nucleic Acids: Synthesis and Characterization of LNA‐T Diol

Pfundheller¹,

Lomholt²

2002

CP Nucleic Acid Chemistry

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Locked nucleic acids (LNAs) are RNA derivatives that have an O-methylene linkage between the 2 and 4 positions of the ribose. This leads to exceptionally high-affinity binding to complementary sequences. LNAs are synthesized from a commercially available sugar, 1,2:5,6-di-O-isopropylidene-a-D-allofuranose. An efficient and simplified procedure is presented for synthesizing a glycol donor that can be used for synthesis of a variety of LNA monomers. Then, as an example, the synthesis of the thymidine analog of LNA from this glycol donor is presented. The protocols give high yields of the desired products and avoid the use of time-consuming column chromatography.

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“…These are 4'-hydroxymethylation of nucleoside 5~-aldehydes (Youssefyeh, Tegg, Verheyden, Jones & Moffatt, 1977) and a Claisen-type rearrangement of nucleoside 4',5'-enamines (Secrist & Winter, 1978). A new approach to produce a series of 4'-C-branched 2~,3t-unsaturated uracil nucleosides has been disclosed quite recently (Haraguchi, Tanaka, Itoh, Saito & Miyasaka, 1992) SAPI85 (Yao, Zheng, Qian, Han, Gu & Fan, 1985).…”

Section: Commentmentioning

confidence: 99%