Organische Chemie Und Bicchemie

Monatshefte für Chemie / Chemical Monthly

, Volume 124, Issue 1, pp 37-53

First online:

Convergent synthesis of 2′,3′-dideoxy-3′-methylthio and 2′,3′-dideoxy-3′-mercapto nucleosides and their disulfide analogues — Potential anti-HIV agents

  • Kim L. DueholmAffiliated withDepartment of Chemistry, Odense University
  • , Youssef L. AlyAffiliated withDepartment of Chemistry, Odense University
  • , Per T. JørgensenAffiliated withDepartment of Chemistry, Odense University
  • , Ahmed A. El-BarbaryAffiliated withDepartment of Chemistry, Odense University
  • , Erik B. PedersenAffiliated withDepartment of Chemistry, Odense University
  • , Claus NielsenAffiliated withRetrovirus Laboratory, Department of Virology, Statens Seruminstitut

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The iodide4(α) or7 synthesized in three steps from 2-deoxy-D-ribose1, has been subjected to a number of nucleophilic substitution reactions producing the 3-benzoylthio-, 3-methylthio- and the 3-thiocyanato-2,3-dideoxy-D-erythro-pentofuranosides8,13 and15, respectively, in addition to the disulfide17 of their 3-mercapto analogue. Subjecting the thiobenzoate8 to the Friedel-Crafts catalyzed silyl Hilbert Johnson reaction in conjunction with the silylated nucleobases of uracil, thymine and N4-isobutyrylcytosine9a–c resulted in the isolation of the 2′,3′-dideoxy-3′-mercapto nucleosides11 and their disulfides12 subsequent to deprotection. The 2,3-dideoxy-3-methylthio-pentofuranoside13 afforded both anomers of the 2′,3′-dideoxy-3′-methylthio nucleosides19 and20 under similar conditions. The first known example of a coupling directly on a 2,3-didehydro-2,3-dideoxyfuranose is presented. 2′,3′-Dideoxy-3′-mercaptocytidine showed protection against HIV-1 in MT-4 cells with ED50=20 µM.


Nucleosides, 2′,3′-dideoxy-3′-mercapto Nucleosides, 2′,3′-dideoxy-3′-methylthio Nucleosides 2′,3′-didehydro-2′,3′-dideoxy Disulfide, bis(2′,3′-dideoxy-nucleosid-3′-yl)

Konvergente Synthese von 2′,3′-Didesoxy-3′-methylthio und 2′,3′-Didesoxy-3′-mercapto-Nucleosiden und ihren Disulfid-Analogen — Potentielle Anti-HIV — Agentien


Die in drei Stufen aus 2-Desoxy-D-ribose hergestellten Jodide4(α) bzw. 7 wurden einer Reihe von nucleophilen Substitutionsreaktionen unterzogen, wobei die 3-Benzoylthio-, 3-Methylthio-und 3-Thiocyanato-2,3-didesoxy-D-erythro-pentofuranoside8,13 und15 zusätzlich zum Disulfid17 ihrer 3-Mercapto-Analogen entstanden. Bei der Friedel-Crafts-katalysierten Silyl-Hilbert-Johnson Reaktion des Thiobenzoats8 in Verbindung mit den silylierten Nucleobasen Uracil, Thymin und N4-Isobutyrylcytosin9a–c entstanden nach der Schutzgruppenentfernung die 2′,3′-Didesoxy-3′-mercapto-Nucleoside11 und ihre Disulfide12. Unter ähnlichen Bedingungen ergaben die 2′,3′-Didesoxy-3′-methylthiopentofuranoside13 beide Anomere der 2′,3′-Didesoxy-3′-methylthionucleoside19 und20. Es wird das erste Beispiel einer direkten Kopplung 2,3-Didehydro-2,3-didesoxyfuranose vorgestellt. 2′,3′-Didesoxy-3′-mercaptocytidin zeigte Schutzwirkung gegenüber HIV-1 in MT-4 Zellen mit ED50=20 µM.