Synthesis of 8-(ω-Hydroxyalkyl)-, 8-(ω-Hydroxyalk-1-enyl)-, and 8-(ω-Hydroxyalk-1-ynyl)adenines Using the tert-Butyldimethylsilyloxymethyl Group, a New and Versatile Protecting Group of Adenine

• Published in: Journal of organic chemistry Vol. 65; no. 23; pp. 7825 - 7832
• Main Authors: Lang, Pascal, Magnin, Géraldine, Mathis, Gérald, Burger, Alain, Biellmann, Jean-François
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 17.11.2000; Amer Chemical Soc
• Subjects: Adenine - analogs & derivatives; Adenine - chemical synthesis; Antiviral Agents - chemical synthesis; Chemistry; Chemistry, Organic; Physical Sciences; Science & Technology; REAGENT; PURINE NUCLEOSIDES; NUCLEOTIDES; ANALOGS; ADENOSINE; 2'-DEOXYADENOSINE; LITHIATION
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo000841o

The synthesis of 12 analogues of adenine substituted at C-8 by an ω-hydroxyalkyl, ω-hydroxyalk-1-enyl, or ω-hydroxyalk-1-ynyl chain of various length has been carried out in five or six steps starting from adenine. The analogues were obtained using a new protecting group of adenine, the tert-butyldimethylsilyloxymethyl group. 9-tert-Butyldimethylsilyloxymethyl-adenine is more soluble than adenine in organic solvents. It was prepared regiospecificaly in two steps from adenine and was amenable to C-8 iodination under basic conditions and to subsequent introduction of the various carbon chains at C-8 by palladium-catalyzed cross-coupling reactions (Stille or Sonogashira). The protecting group was removed under acidic conditions, thus demonstrating its versatility.