Enantioseparation on Amino Alcohol‐Derived Stationary Phases by Supercritical Fluid Chromatography and High‐Performance Liquid Chromatograpy

Abstract

Previous studies have shown that amino alcohol‐derived chiral stationary phases can effectively separate some chiral samples. With the aim at improving the chiral separation, in this study, the composition and type of the mobile phase and the particle size of the stationary phase are changed, and the analytical method is carried out in parallel using high‐performance liquid chromatograpy (HPLC) and supercritical fluid chromatography (SFC). By changing the type and composition of the mobile phase and reducing the particle size of the stationary phase, optimal separation and analysis conditions are obtained simultaneously for HPLC and SFC experiments. In particular, for a particle size of 3 μm, the resolution increases for dinitrobenzoyl phenylglycinol and 2,2,2‐trifluoro‐1‐(9‐anthryl)ethanol. Moreover, replacing the organic modifier from methanol to isopropanol allows obtaining better results in the SFC experiments of dinitrobenzoyl phenylglycinol, dinitrobenzoyl leucinol, and 2,2,2‐trifluoro‐1‐(9‐anthryl)ethanol GTOC,Chiral separation by SFC and HPLC.

Amino alcohol‐derived chiral stationary phases

“…α-Amino acid-derived amino alcohol-based CSPs used in the chiral separation have been frequently reported by our laboratory. 67,[82][83][84][85][86][87][88][89] The first Pirkle-type π-acidic α-amino acid-derived amino alcohol-based CSP prepared by our group was a phenylglycinol 3,5-dinitrobenzoyl derived CSP 17 (Figure 3). 82 CSP 17 was prepared by connecting the N-(3,5-dinitrobenzoyl)-(R)-phenylglycinol to the silica gel using isocyanatopropyltriethoxysilane through a carbamate linkage by following the same synthetic procedure as the (1S,2R)-norephedrine 3,5-dinitrobenzoyl derived CSP 1.…”

“…[69][70][71][72][73][74][75][76][77][78][79][80][81] The α-amino alcohol-based CSPs have been frequently reported in chiral separation without the use of the ligand exchange mode. 67,[82][83][84][85][86][87][88][89] First, Pirkle-type π-acidic CSP prepared by our group, based on an α-amino alcohol, was an (R)-phenylglycinol 3,5-dinitrobenzoyl derived CSP. 82 Thereafter, starting materials such as the (S)-leucinol, (S)alaninol, (1S,2R)-norephedrine, (1S,2R)-ephedrine, and (S)-tert-leucinol were used to prepare amino alcohol-based 3,5-dinitrobenzoyl-derived CSPs.…”

“…82 Thereafter, starting materials such as the (S)-leucinol, (S)alaninol, (1S,2R)-norephedrine, (1S,2R)-ephedrine, and (S)-tert-leucinol were used to prepare amino alcohol-based 3,5-dinitrobenzoyl-derived CSPs. 67,[83][84][85][86][87][88] Amino alcoholbased CSPs with a large adamantyl group, but without π-acidic or π-basic groups have been reported. 89 Similarly, the quinine and quinidine from the family of cinchona alkaloids, comprised of amino and alcohol functional groups, have also been used to prepare chiral catalysts and CSPs.…”

“…Studies using amino alcohols to prepare CSPs for chiral separations have been reported by Yuki et al, 70,71 Mamiany et al, 105 Hyun et al, 65,66,[72][73][74][75][76][77][78][79] and Ryoo et al 67,[73][74][75][76][77][82][83][84][85][86][87][88][89] The development of ligand-exchange CSPs based on amino alcohols and their derivatives was reviewed in 2018 based on the work of Hyun. 72 To the best of our knowledge, there have been no further studies on amino alcohol-based CSPs other than those mentioned above to this date.…”

Recent progress in the development of chiral stationary phases for high‐performance liquid chromatography

“…Recently, several low molecular weight CSPs derived from the amino acid, amino alcohol, amine, peptoid, and binaphthol have been reported for HPLC enantiomeric separation (Figure 5) [101][102][103][104][105][106][107][108][109][110]. Ryoo and Kim [101] and Ryoo and Heo [102]prepared (R)-phenylglycinol, (R)phenylglycine, (S)-leucinol, and (S)-leucine derived CSPs (Figure 5 of C 3 symmetric CSP 10a and CSP 10b were better than those of CSP 9a and CSP 9b probably because the phenyl group attached to the amide linkage interrupts hydrogen bonding interactions between the amide hydrogen, which is replaced by the phenyl group, and the chiral analytes, thereby inducing an effective interaction at a position near the chiral center [103]. Nevertheless, the exact role of the amide N-phenyl group is not yet understood.…”