| Chiral is one of the fundamental properties of nature. It comes from the Greek word,"cheir", which means"hands". The two enantiomers of chiral drug may have different effect on living organisms. In this context, the preparation of individual enantiomers has become more and more important.Chromatographic enantioseparation on chiral stationary phases (CSPs) represents one of the most direct and facile approaches for the determination of enantiomeric purity and the preparation of pure enantiomeric drugs. So, the study of chiral recognition mechanism and the synthesis of CSPs are very important. This article mainly discussed the enantioseparations of 1,1'-bi-2-naphthol (BINOL) on two polysaccharide-based CSPs, including Chiralpak IA and Chiralcel OD-H. And three chiral stationary phases were synthesized, including coated cellulose tris-cinnamate CSP, bonded binaphthol and glucose CSPs.1. In Chapter l, the importance and the methods of chiral separation were briefly introduced. The literatures of two kinds of CSPs, polysaccharide derivative and Pirkle type CSPs, were briefly reviewed. And the chromatographic parameters and chiral separation theory were introduced.2. The enantioseparations of 1,1'-bi-2-naphthol (BINOL) were performed on polysaccharide-based chiral stationary phases, Chiralpak IA and Chiralcel OD-H, under normal-phase mode. The effects of polar modifier in the mobile phase on the retention, enantioseparation and elution order were investigated in detail. On the immobilized polysaccharide-based chiral stationary phase, Chiralpak IA, temperature-induced inversion of elution order for BINOL was observed directly. When n-hexane/2-propanol (92/8, v/v) was used as mobile phase, temperature-induced inversion of elution order was observed distinctly (Fig. 2B). R-BINOL eluted first when column temperature was below 20 0C, and beyond 45 0C S-BINOL eluted first. On the coated polysaccharide-based chiral stationary phase, Chiralcel OD-H, solvent-induced reversal of elution order for BINOL was observed. When linear alcohols were adopted, R-BINOL was always eluted first. S-BINOL was eluted first when 2-propanol was used as a polar modifier. Enantioseparation could not be obtained when sec-butyl alcohol or tert-butyl alcohol was used as a polar modifier. In this work, temperature-induced and solvent-induced inversions of elution order for BINOL were observed directly. In a domain, the enantioseparations can not be obtained. This domain can be named"temperature-induced blind zone"or"solvent-induced blind zone"in chiral recognition. In this zone, chiral recognition becomes invalid. Farther away from the blind zone, better chiral recognition should be obtained. It is important to anticipate when such temperature-induced and solvent-induced inversions of elution order would occur. Another meaningful aspect is, how to shift one enantioseparation into suitable domain which is far away from the"blind zone".3. Cellulose tris-cinnamate was coated onto the epoxide silica gel as a chiral stationary phase. The effect of the partical size of silica gel on the enantioseparation was studied. HPLC experiments revealed that the synthesized CSP having a small-pore silica support afforded chiral recognition ability fully comparable to the CSP using the conventional large-pore silica as the support. For several racemates, including a cyclic ether of binaphthol, (9S,10S)-9,10-dihydrophenanthrene, hydrobenzoin and naproxen, the enantioseparations on the self-prepared coated cellulose tris-cinamate CSP were good.4. Binaphthol (BINOL) and glucose were chemically attached to the epoxidation silica gel as chiral stationary phases. The productions were characterized by element analysis (EA) and thermogravimetric analysis (TG). 2-Naphthyl ethanol and a cyclic ether of binaphthol exhibited a weak enantioseparation on these two CSPs. Further experiments must be performed to improve the bonded amount of the chiral selectors, or to obtain various derivatives of these CSPs.
|
PDF Full Text Request