Collect. Czech. Chem. Commun. 2004, 69, 918-932

Synthesis of Racemic 2-Hydroxy-4- and 2-Hydroxy-5-(hydroxymethyl)cyclohexane Pyrimidine C-Nucleoside Analogues

Michal Šála, Hubert Hřebabecký*, Milena Masojídková and Antonín Holý

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


The oxirane ring opening of 3-[(benzyloxy)methyl]-7-oxabicyclo[4.1.0]heptane with sodium salt of diethyl malonate followed by treatment with TsOH gave (3aR*,6R*,7aS*)-6-[(benzyloxy)methyl]hexahydro-1-benzofuran-2(3H)-one (3a) and (3aR*,5R*,7aS*)-5-[(benzyloxy)methyl]hexahydro-1-benzofuran-2(3H)-one (3b). Lactones 3a and 3b were formylated and then treated with thiourea or guanidine to give, after deprotection, racemic 5-[2-hydroxy-4- and 2-hydroxy-5-(hydroxymethyl)cyclohexyl]-2-thiouracil (5a and 5b) or -isocytosine (12a and 12b). Simple transformations of the 2-thiouracil derivative led to uracil (7a and 7b), 4-thiouracil (9a and 9b), and cytosine derivatives (10a and 10b).

Keywords: Carbanucleosides; Carbocyclic nucleosides; Nucleosides; Cyclohexanes; C-Nucleosides; Pyrimidines.

References: 49 live references.