Process for recovery of the desired cis-1,3-oxathiolane nucleosides from their undesired trans-isomers

A process for the preparation of 1,3-oxathiolane nucleoside analogues in predominantly the cis-form, from mixture of cis-/trans-1,3-oxathiolane nucleosides or their protected derivatives thereof, comprising:(i) treatment of the cis-/trans-1,3-oxathiolane nucleosides (or protected derivatives thereof) with a pyrimidine base (or it derivatives thereof) and an acid,(ii) adding a suitable acid to the obtained cis-/trans-mixture of isomers,(iii) selective crystallization of the desired cis-isomer salt from a solvent or combination of solvents, and(iv) treatment of the predominantly cis-isomer salt with a suitable base to offer the free 1,3-oxathiolane nucleosides, and thereafter optionally repeating steps (i) to (iv) inclusive.