Regioselective Synthesis And Chiral Recognition Of Amylose Derivatives As Chiral Stationary Phases

Chiral recognition and enantioseparation of chiral drugs has attracted more and more attention due to the different pharmacokinetics, physiological, toxicological, and therapeutic effects of a pair of enantiomers. Among the methods of chiral separation, chiral stationary phases (CSPs) using high-performance liquid chromatography (HPLC) is recognized as one of the most effective and reliable tool to obtain pure enantiomers on analytical and industrial scales A large number of amylose derivatives have been used as coated-type CSPs for high-performance liquid chromatography, which show excellent chiral recognition ability.However, the conventional coated-type CSPs are restricted in the usage of organic solutions.In order to investigate the influence of immobilized-type CSPs on the chiral recognition ability, a series of amylose derivatives bearing an amount of vinyl groups at 6- position were synthesized in this paper.A series of amylose derivatives bearing of four kinds of phenylcarbamate groups at the 2-,3-position, partial vinyl groups and partial phenylcarbamate groups at the 6-position were regioselectively synthesized. The chemical structures of the derivatives were characterized by FT-IR spectroscopy and 1H NMR, which could be verified that they were target amylose derivatives.Amylose derivatives were coated on aminopropyl silica gel, four of these CSPs were made into immobilized-type CSPs via radical polymerization of vinyl groups at the 6-position.Coating efficiency and immobilization efficiency were estimated by thermogravimetric analysis (TGA). The chiral recognition abilities of the amylose derivatives were evaluated as CSPs with nine racemates by HPLC. The results show the differences in the chiral recognition ability between different CSPs. It is probably due to the polar substitution of phenylcarbamate derivatives of amylose resulting in the different interactions between CSPs and racemates. The more vinyl groups, the higher immobilization efficiency, the lower chiral recognition ability. When THF or CHCl3 was added in the eluent, immobilized-type CSPs showed higher chiral recognition ability for some racemates. The resolution of racemate 9 on CSP-2 was improved using the eluent containing THF or CHCl3, which cannot be used in the conventional coated-type CSPs. Baseline separation of racemates 2 and 7 was achieved on the CSP-3 when CHCl3 was introduced to the eluent.