Collect. Czech. Chem. Commun. 2009, 74, 1425-1441
Published online 2009-09-21 19:41:57

New carbocyclic nucleoside analogues built on a bicyclo[2.2.2]octane-2,2-dimethanol template

Hubert Hřebabecký*, Martin Dračínský and Antonín Holý

Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, v.v.i., Flemingovo nám. 2, 166 10 Prague 6, Czech Republic


(1R*,4S*,6S*)-6-(6-Chloro-9H-purin-9-yl)bicyclo[2.2.2]octane-2,2-dimethanol (22) and (1R*,4R*,5S*)-5-(6-chloro-9H-purin-9-yl)bicyclo[2.2.2]octane-2,2-dimethanol (17) were prepared from (1R*,4R*)-bicyclo[2.2.2]oct-5-ene-2,2-dimethanediyl dibenzoate (7) using two approaches. The first procedure consists in hydroboration of 7, separation of obtained 6-exo-hydroxy derivative 8 and 5-exo-hydroxy derivative 9, conversion of 8 and 9 to endo-hydroxy derivatives 12 and 13, respectively, and the Mitsunobu reaction with 6-chloropurine. Only 5-(6-chloropurinyl) analogue 16 was obtained in an acceptable yield. The target analog 17 was prepared by reductive debenzoylation of 16. The further reactions were hydroboration of 7, treatment with hydroxylamine-O-sulfonic acid and debenzoylation. Chloropurine analogues 17 and 22 were built on the obtained 6-exo-amino- and 5-exo-aminobicyclo[2.2.2]octane-2,2-dimethanols 18 and 19, respectively. Compounds 17 and 22 were converted to adenine (23, 24) and 6-(cyclopropylamino)purine analogues (25, 26).

Keywords: Nucleosides; Carbocyclic nucleosides; Purines; Adenine; 6-Chloropurine; 6-(Cyclopropylamino)purine; Hydroboration; Mitsunobu reaction.

References: 31 live references.