Preparation and evaluation of regioselectively substituted amylose derivatives for chiral separations

Abstract

Six novel regioselectively substituted amylose derivatives with a benzoate at 2-position and two different phenylcarbamates at 3- and 6-positions were synthesized and their structures were characterized by H nuclear magnetic resonance (NMR) spectroscopy. Their enantioseparation abilities were then examined as chiral stationary phases (CSPs) for high-performance liquid chromatography (HPLC) after they were coated on 3-aminopropyl silica gels. Investigations indicated that the substituents at the 3- and 6-positions played an important role in chiral recognition of these amylose 2-benzoate serial derivatives. The derivatives demonstrated characteristic enantioseparation and some racemates were better resolved on these derivatives than on Chiralpak AD, which is one of the most efficient CSPs, utilizing coated amylose tris(3,5-dimethylphenylcarbamate) as the chiral selector. Among the derivatives prepared, amylose 2-benzoate-3-(phenylcarbamate/4-methylphenylcarbamate)-6-(3,5-dimethylphenylcarbamate) exhibited chiral recognition abilities comparable to that of Chiralpak AD and may be useful CSPs in the future. The effect of mobile phase on chiral recognition was also studied. In general, with the decreased concentration of 2-propanol, better resolutions were obtained with longer retention times. Moreover, when ethanol was used instead of 2-propanol, poorer resolutions were often achieved. However, in some cases, improved enantioselectivity was achieved with ethanol rather than 2-propanol as the mobile phase modifier.

Enantiomer separation on novel cellulose derivatives bearing regioselective phenylcarbamate groups

“…Another example is the resolution of racemate 5, which cannot be resolved on 1b (α, 1.00), was resolved on CTCMPC (α, 1.20). Investigations [7][8][9][10][11][13][14][15][16] have revealed that it is not unusual to obtain better resolutions with heterogeneously substituted polysaccharide derivatives and this phenomenon is also observed in this study. For instance, the α value for racemate 3 on 1b (2.41) was higher than that on CTCMPC (2.09).…”

“…Among them, homogeneously substituted benzoates and phenylcarbamates of cellulose and amylose are the most often used materials, that is, they have the same substituent at the 2‐, 3‐, and 6‐positions of a glucose unit. In order to broaden the range of application on a same CSP, regioselectively substituted polysaccharide derivatives have also been utilized as CSPs in HPLC, leading to interesting data in regard of enantioselectivity [7–19]. CSPs based on regioselectively substituted polysaccharide derivatives were first reported by Kaida and Okamoto [7].…”

“…Among them, homoge-Article Related Abbreviations: CPM, chiral packing material; CSP, chiral stationary phase; CTCMPC, cellulose tris(3-chloro-4-methylphenylcarbamate); DMA, N,N-dimethylacetamide; TGA, thermogravimetric analysis; TrCl, triphenylmethyl chloride neously substituted benzoates and phenylcarbamates of cellulose and amylose are the most often used materials, that is, they have the same substituent at the 2-, 3-, and 6-positions of a glucose unit. In order to broaden the range of application on a same CSP, regioselectively substituted polysaccharide derivatives have also been utilized as CSPs in HPLC, leading to interesting data in regard of enantioselectivity [7][8][9][10][11][12][13][14][15][16][17][18][19]. CSPs based on regioselectively substituted polysaccharide derivatives were first reported by Kaida and Okamoto [7].…”

“…From then on, a number of regioselectively substituted polysaccharide derivatives [8][9][10][11] have been synthesized and some racemates were better resolved on these derivatives as compared to the corresponding homogeneously substituted ones. Based on the selective esterification at the 2-position of amylose [12], a novel class of amylose derivatives [13][14][15][16] with three different groups at the 2-, 3-, and 6-positions have been synthesized and some of them exhibited higher or comparable chiral resolving abilities to the commercially available amylose-based column, Chiralpak AD. Additionally, CSPs based on immobilized regioselectively substituted amylose derivatives were reported [17,18].…”

Separation of ephedrine and pseudoephedrine enantiomers using a polysaccharide‐based chiral column: A normal phase liquid chromatography–high‐resolution mass spectrometry approach

“…In spite of the recent advances in the development of chiral stationary phases contain chemical cross linking between the polysaccharide and silica supports, the enantiomeric analysis of underivatized ephedrines by using chiral columns has received a limited attention. So it is very much necessary to develop the direct methods for the separation and enantiomeric determination of ephedrines and ephedrine‐type compounds.…”