Engineering Cyclodextrin Clicked Chiral Stationary Phase for High-Efficiency Enantiomer Separation

Abstract

The separation of racemic molecules is of crucial significance not only for fundamental research but also for technical application. Enantiomers remain challenging to be separated owing to their identical physical and chemical properties in achiral environments. Chromatographic techniques employing chiral stationary phases (CSPs) have been developed as powerful tools for the chiral analysis and preparation of pure enantiomers, most of which are of biological and pharmaceutical interests. Here we report our efforts in developing high-performance phenylcarbamated cyclodextrin (CD) clicked CSPs. Insights on the impact of CD functionalities in structure design are provided. High-efficiency enantioseparation of a range of aryl alcohols and flavanoids with resolution values (Rs) over 10 were demonstrated by per(3-chloro-4-methyl)phenylcarbamated CD clicked CSP. Comparison study and molecular simulations suggest the improved enantioselectivity was attributed to higher interactions energy difference between the complexes of enantiomers and CSPs with phenylcarbamated CD bearing 3-chloro and 4-methyl functionalities.

Cationic cyclodextrin clicked chiral stationary phase for versatile enantioseparations in high-performance liquid chromatography

“…In comparison to CCC3M4-CSP (0.37 mol/m 2 surface loading), MPCCC3M4-CSP showed lower surface loading on silica gel, which might be attributed to repulsion effect of the chiral selector from the silica gel caused by the cationic moiety. Meanwhile, by eluting toluene as model sample using pure methanol as mobile phase at 1.0 mL/min, the as-packed MPCCC3M4-CSP column delivered a slightly lower column efficiency of 11586 plates/m than CCC3M4-CSP one [26].…”

“…When electron-withdrawing or donating substitutes are introduced onto the phenyl ring, the change in acidity of N H group and electron density of carbonyl group would affect the stability of inclusion complexes through other interactions such as hydrogen bonding and steric hindrance. The functionality tuned enantioseparations of CD clicked CSPs have been systematically reported in our recent study [26]. The phenylcarbamoylated CD bearing 3-chloro and 4-methyl functionalities http exhibited the best enantioselectivity and chiral resolution for CD clicked CSPs.…”

Functionalities tuned enantioselectivity of phenylcarbamate cyclodextrin clicked chiral stationary phases in HPLC

“…HPLC‐grade trifluoroacetic acid (TFA) and triethylamine (TEA) were purchased from J&K (Shanghai, China). All racemates were procured from J&K. Two CSPs were prepared in our lab and packed into columns (4.6 × 250 mm) accordingly . Typically, 6 A –azido‐β‐cyclodextrin was functionalized by reacting with 4‐chloro‐3‐methylphenylisocyanate or 5‐chloro‐2‐methyl phenylisocyanate in dry pyridine.…”

“…The functionalities modulated enantioselectives of CD clicked CSPs have been a research theme in our group . A series of mixed chloro‐ and methyl‐substituted phenylcarbamate β‐CD clicked CSPs has been developed . The introduction of an electron‐donating methyl group or an electron‐withdrawing halogen at the 3‐ and/or 4‐position of the phenyl ring on phenylcarbamate polysaccharide (cellulose and amylose) CSPs was found to improve their chiral recognition ability towards many racemates …”

“…In order to reveal the functionalities‐tuned enantioselectivities in multiple modes HPLC, per(4‐chloro‐3‐methyl)phenylcarbamate CD clicked CSP (CCC4M3‐CSP) and per(3‐chloro‐4‐methyl)phenylcarbamate one (CCC3M4‐CSP) as well native CD clicked CSP were developed for the enantioseparation of a large library of racemates . We herein further report the comparison study of CCC4M3‐CSP and per(2‐chloro‐5‐methyl)phenylcarbamate clicked CSP (CCC2M5‐CSP) for enantioseparation in both NP and RP modes of HPLC.…”