A low-temperature, photoinduced thiol-ene click reaction: a mild and efficient method for the synthesis of sugar-modified nucleosides

Organic & Biomolecular Chemistry
Miklós BegeAnikó Borbás

Abstract

Sugar-modified nucleosides are prime synthetic targets in anticancer and antiviral drug development. Radical mediated thiol-ene coupling was applied for the first time on nucleoside enofuranoside derivatives to produce a broad range of thio-substituted d-ribo, -arabino, -xylo and l-lyxo configured pyrimidine nucleosides. In contrast to the analogous reactions of simple sugar exomethylenes, surprisingly, hydrothiolation of nucleoside alkenes under the standard conditions of various initiation methods showed low to moderate yields and very low stereoselectivity. Optimizing the reaction conditions, we have found that cooling the reaction mixture has a significant beneficial effect on both the conversion and the stereoselectivity, and UV-light initiated hydrothiolation of C2'-, C3'- and C4'-exomethylene derivatives of nucleosides at -80 °C proceeded in good to high yields, and, in most cases, in excellent diastereoselectivity. Beyond the temperature, the solvent, the protecting groups on nucleosides and, in some cases, the configuration of the thiols also affected the stereochemical outcome of the additions. The anomalous l-lyxo diastereoselectivity observed upon the addition of 1-thio-β-d-gluco- and galactopyranose derivatives ont...Continue Reading

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Citations

Oct 7, 2020·Organic & Biomolecular Chemistry·Miklós BegeAnikó Borbás
Jun 13, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Miklós BegeAnikó Borbás
Jan 23, 2020·International Journal of Molecular Sciences·Magdolna CsávásAnikó Borbás
Feb 23, 2020·Organic Letters·Guillaume ClavéMichael Smietana
Apr 10, 2021·Chemical Reviews·Benjamin D FairbanksChristopher N Bowman

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Methods Mentioned

BETA
column chromatography
NMR

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