Enantiomeric separation of biaryl atropisomers using cyclofructan based chiral stationary phases

Abstract

Normal phase chiral HPLC methods are presented for the enantiomeric separation of 30 biaryl atropisomers including 18 new compounds recently produced via a novel synthetic approach. Three new cyclofructan based chiral stationary phases were evaluated. Separations were achieved for all but six analytes and the LARIHC™ CF6-P alone provided 15 baseline separations. Effects of polar modifiers and temperature effects also were studied. Apparent thermodynamic parameters were determined by van't Hoff plots. Preparative scale methods were developed and employed resulting in the first ever isolation of these novel atropisomers in their pure enantiomeric form. Insights into the mechanism of retention and chiral discrimination are presented.

Separation of therapeutic peptides with cyclofructan and glycopeptide based columns in hydrophilic interaction liquid chromatography

“…Their different functionalities are summarized in Fig. S1 and include native cyclofructan 6 (CF6) (Frulic TM N) [27][28][29], an isopropyl carbamate modified cyclofructan 6 stationary phase (Larihc TM CF6-P) found to be excellent for chiral [30] as well as HILIC separations [31], and a 4-chloromethyl-styrene-divinylbenzene resin based CF6 column [32,33].…”

Recent progress of chiral stationary phases for separation of enantiomers in gas chromatography

“…Compared with native CFs, which have rather limited chiral recognition ability, the chiral stationary phases of aliphatic and aromatic functionalized CF6 with unique and very different selectivities can separate a very broad range of racemic compounds. Since then, a series of new chiral stationary phases using different CF derivatives as chiral selectors have been further developed in HPLC , GC , and CE by Armstrong et al.…”

Chromatographic resolution of atropisomers for toxicity and biotransformation studies in pharmaceutical research

“…The concept of atropisomerism in drug discovery has been properly discussed in several papers [4][5][6]. The detailed investigations on the rotational barriers in relation to the substituents and substitution pattern of biphenyl congeners were carried out by the research groups of Schurig et al [7] and König et al [8]. Like traditional racemic material, atropisomers with a large energy barrier can be isolated by traditional enantioselective chromatography, crystallization, or classic resolution.…”