Chromatographic Enantioresolution of Six Purine Derivatives Endowed with Anti-Human Breast Cancer Activity

Three (R,S)-9-(2,3-dihydro-1,4-benzoxathiin-3-ylmethyl)-9H-purine derivatives (1–3) and three (R,S)-9-(2,3-dihydro-1,4-benzoxathiin-2-ylmethyl)-9H-purine derivatives (4–6) showed relevant activity against human breast cancer cell line MCF-7, when assayed as racemates. The relevant structural analogy among these compounds stimulated us to evaluate and compare their chromatographic behaviour with five polysaccharide-based chiral stationary phases (CSPs). For a column screening purpose, four cellulose-based (Chiralcel OD-H, Chiralpak IB, Lux Cellulose-2, and Sepapak-4; CSPs 1–4, respectively) and an amylose-based (Lux Amylose-2; CSP 5) CSPs were initially assayed by employing the same “standard” eluent mixture. With CSP 2, the performance from “non standard” eluent systems was also evaluated. The different type and position of the substituents onto the carbamate moiety, the coated or immobilized nature of the modified polymer chain, and the different type of winding as well as the eluent composition were found to deeply affect the enantiorecognition mechanism. While the different winding of the polymer and the derived different morphology of the binding cleft in the 2,5-disubstituted chloromethyl phenyl carbamate amylose-based CSP 5 was found to be unsuited to get profitable enantio-discriminations of all the analyzed compounds, CSP 3 and CSP 4 produced the highest α and R _S values in the enantioselective analysis of four out of six racemates (that is 1–3 and 6). In CSP 2, the conformational change of the polysaccharide chain upon immobilization produced a profound influence on the chromatographic behaviour of compounds 1–6. A relevant improvement of the enantioresolution quality of CSP 2 was obtained when used in combination with “non standard” solvents as constituents of the mobile phase mixture.