Synthesis of 8-(omega-Hydroxyalkyl)-, 8-(omega-hydroxyalk-1-enyl)-, and 8-(omega-hydroxyalk-1-ynyl)adenines using the tert-butyldimethylsilyloxymethyl group, a new and versatile protecting group of adenine.
The synthesis of 12 analogues of adenine substituted at C-8 by an omega-hydroxyalkyl, omega-hydroxyalk-1-enyl, or omega-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.
Lang
P
P
Laboratoire de Chimie Organique Biologique, UMR 7509, Faculté de Chimie, Université Louis Pasteur, 1 rue Blaise Pascal, 67008 Strasbourg Cedex, France.
Magnin
G
G
Mathis
G
G
Burger
A
A
Biellmann
J F
JF
D000225:Adenine / Q000031:analogs & derivatives / Q000138:chemical synthesis*; D000998:Antiviral Agents / Q000138:chemical synthesis*
D000998:Antiviral Agents; D000225:Adenine