The loss of TEAH + cation from certain nucleotide analogues

Phosphorus esters of biomolecules are often isolated in a form of triethylammonium salts, which are usually stable, amorphous solids of good solubility both in water and organic solvents, and are obtained directly after chromatography performed in the presence of triethylamine. However, during our recent studies on nucleoside phosphoramidates of type 1 we consistently isolated them as free acids instead of the expected TEAH+ salts (Fig. 1).1 Th is may aff ect the stability and solubility of a product, lead to acidifi cation of its solutions and cause false calculations due to decrease of the molecular mass. Th e lability of the TEAH+ cation in these compounds was assigned to an equilibrium in which free TEA was released to the solution and evacuated during concentration, leaving behind the nucleotidic counterpart that may exist in several putative forms 1A.1 Some further observations regarding this phenomenon are outlined in this communication.