Collect. Czech. Chem. Commun. 1999, 64, 1485-1496

Synthesis of Carba Analogues of 2'-Deoxy-4'-C-(hydroxymethyl)nucleosides

Hubert Hřebabecký* and Antonín Holý

Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, 166 10 Prague 6, Czech Republic


Racemic dimethyl 2-hydroxy-4-[5-methyl-2(1H),4(3H)-dioxopyrimidin-1-yl]- (7a and 8a) and dimethyl 4-(6-aminopurin-9-yl)-2-hydroxycyclopentane-1,1-dicarboxylates (7b and 8b) were prepared by addition of sodium salt of thymine and adenine, respectively, to dimethyl (Z)-(4-oxobut-2-en-1-yl)malonate (1). Reduction of the diesters with sodium borohydride in methanol in the presence of sulfuric acid gave corresponding racemic 2,2-bis(hydroxymethyl)-4-[5-methyl-2(1H),4(3H)-dioxopyrimidin-1-yl]- (14a and 15a), 4-(6-aminopurin- 9-yl)-2,2-bis(hydroxymethyl)cyclopentan-1-ol (14b and 15b), methyl (±)-cis-2-hydroxy- 1-hydroxymethyl-4-[5-methyl-2(1H),4(3H)-dioxopyrimidin-1-yl]- (13a), and methyl (±)-cis-4-(6-aminopurin-9-yl)-2-hydroxy-1-hydroxymethylcyclopentan-1-carboxylate (13b), respectively.

Keywords: Carbanucleosides; Carbocyclic nucleosides; 4'-C-Branched nucleosides; Cyclopentanes; Nucleosides; Reductions; Additions.