Orotic acid derivatives with improved water - solubility

Orotic acid derivatives of type where R1, R2 = either or both a (possibly arylated) 2-hydroxyalkyl group with 2-5C atoms. and if not, either H or C1-3 alkyl, and Z = H or a cation, together with the S-lactones of compounds hydroxyalkylated on N-1, have much higher aq. solubilities than orotic acid and its salts, and are thus superior for pharmaceutical use. The preferred compounds are potassium 3-(2-hydroxpropyl) orotate (126g/100 ml H2O) and 1-(2-hydroxyethyl)-3-methyl-orotic acid lactone; compare Na orotate 0.36g/100 ml H2O. The compounds are made by treatment of orotic acid or its N-alkyl derivatives in alkaline solution with a 1,2-epoxide, followed by lactonisation with strong acid (and separation of the N-1 and N-3 derivatives, if appropriate, by treatment with buffer or pH 4-4.5, when the lactone remains undissolved.