Evaluation of chiral dehydroabietic acid-terminated tetra-arm PEG as an assisted phase-forming polymer and chiral selector for the enantioseparation of propranolol racemate in aqueous two-phase systems

•A chiral ATPS was constructed using 4-arm PEG-DHAA as a phase-forming polymer and chiral selector.•Propranolol enantiomers were separated through liquid–liquid enantioselective extraction via the chiral ATPS.•The chiral ATPS can be reused, with potency in enantiomeric recognition and liquid–liquid enantioselective extraction. In this work, we successfully synthesized a chiral dehydroabietic acid-terminated tetra-arm PEG (4-arm PEG-DHAA) and utilized it to construct a chiral aqueous two-phase system (ATPS) alongside PEG2000 and (NH4)2SO4. The 4-arm PEG-DHAA served as both an assisted phase-forming polymer and a chiral selector. This ATPS can be employed for chiral recognition and liquid–liquid enantioselective extraction of the propranolol enantiomers. The effects of four primary factors, namely initial rac-propranolol concentration, extraction temperature, system pH, and the concentration of 4-arm PEG-DHAA on enantioseparation, were thoroughly evaluated. Furthermore, the optimization of extraction conditions was conducted using the response surface methodology. The results indicated that the chiral ATPS has better and higher enantioselectivity, with a one-step chiral extraction achieving an e.e. up to 57% and a yield exceeding 73% for S-isomers under the optimized conditions. In addition, the chiral ATPS can be regenerated through simple back-extraction with diethyl ether and reused at least five times, achieving similar enantioselective extraction results. This research presents a valuable enantioseparation approach for propranolol enantiomers via liquid–liquid enantioselective extraction using the chiral ATPS.