Methyl 4-thio-beta-D-arabinofuranoside (I) was converted to the tribenzoate ester (II) by means of benzoyl chloride and pyridine, and then treated with HBr in AcOH to give the arabinofuranosyl bromide (III). Displacement of bromide ion in (III) by bis(trimethylsilyl)-N-acetylcytosine (IV) at 130 C led to an anomeric mixture of nucleosides from which the required beta-anomer (V) was isolated by chromatography. Finally, deprotection of the benzoate esters and acetamido group of (V) was performed with methanolic ammonia at 0 C.

In a related procedure, arabinofuranosyl bromide (III) was condensed with bis(trimethylsilyl)uracil (VI) to afford, after chromatographic separation, the beta-nucleoside (VII). Subsequent treatment of (VII) with P2S5 produced the 4-thiouridine analogue (VIII). Then, treatment of this derivative with methanolic ammonia at 110 C in a sealed tube yielded the title arabinofuranosyl citosine.

An alternative procedure consisted in the condensation of tetraacetyl 4-thio-D-ribofuranose (IX) with silylated cytosine (IV) in the presence of SnCl4. After chromatographic separation of the major beta-nucleoside (X), deprotection of its acetyl groups with methanolic ammonia yielded the ribofuranoside (XI). In order to achieve the required epimerization of the 2'-hydroxyl group of (XI), cyclization between the 2 and 2' positions by means of POCl3 in DMF produced the cyclic derivative (XII). Finally, ring opening of (XII) by aqueous ammonia yielded the target arabinofuranosyl derivative.