Liquid chromatographic resolution of 3‐amino‐1,4‐benzodiazepin‐2‐one derivatives on various Pirkle‐type chiral stationary phases

Abstract

The two enantiomers of N-acyl amide and N-ureide derivatives of 3-amino-5-phenyl-1,4-benzodiazepin-2-ones, which have been known to show anti-respiratory syncytial virus (RSV) activity, were resolved on seven different Pirkle-type chiral stationary phases (CSPs) with the use of 10% isopropyl alcohol in hexane as a mobile phase. Among the seven Pirkle-type CSPs, the one based on (S)-leucine derivative named as N-Phe-L-Leu was found to be most successful, the separation factors (α) and the resolutions (R(S) ) for seven analytes being in the range of 1.78-4.21 and 5.94-15.08, respectively. By resolving N-benzyloxycarbonyl derivatives of 3-amino-5-phenyl(or 5-methyl)-1,4-benzodiazepin-2-ones on Pirkle-type CSPs, the phenyl ring at the 5-position and the NH hydrogen at the 1-position of analytes were found to play an important role in the chiral recognition.

Liquid chromatographic resolution of 3‐amino‐1,4‐benzodiazepin‐2‐ones on crown ether‐based chiral stationary phases

“…These results indicate that the electron density of the 5-phenyl ring or the benzo ring of 3-amino-5-phenyl-1,4-benzodiazepin-2-ones does not influence the chiral recognition significantly. Interestingly, the chiral recognition behaviors of the three CSPs were also not changed significantly even though the 5-phenyl group of the analyte (4) was replaced by the 5-methyl group (8). In contrast, analyte 9, in which the N-H hydrogen of analyte 4 is replaced by a methyl group, was resolved only slightly on CSP 1, whereas it was resolved even better than analyte 4 on CSP 2 and CSP 3.…”

“…11,20,21 The void volume was determined by injecting 2,6-lutidine as an unretained analyte. Analytes, 3-amino-5-phenyl (or 5-methyl)-1,4-benzodiazepin-2-ones (4-9) shown in Figure 2, were prepared by treating N-benzyloxycarbonyl derivatives of 3-amino-5-phenyl-1,4-benzodiazepin-2-ones, which were prepared in the previous study, 8 with hydrogen bromide in acetic acid at 70 C. Injection samples were prepared by dissolving each analyte in methanol at a concentration of 1.0 mg/ml, and an injection size was typically 2.0 ml.…”

“…Among various methods, the liquid chromatographic chiral stationary phase (CSP) method has been emerged as one of the major workhorses for the determination of the enantiomeric composition or purity of optically active chiral compounds . Previously, N ‐acyl amide or N ‐ureide derivatives of 3‐amino‐5‐phenyl‐1,4‐benzodiazepin‐2‐ones have been resolved on Pirkle‐type CSPs . However, the direct resolution of 3‐amino‐5‐phenyl‐1,4‐benzodiazepin‐2‐ones on CSPs has not been performed.…”

“…7 Previously, N-acyl amide or N-ureide derivatives of 3-amino-5-phenyl-1, 4-benzodiazepin-2-ones have been resolved on Pirkle-type CSPs. 6,8 However, the direct resolution of 3-amino-5-phenyl-1,4-benzodiazepin-2-ones on CSPs has not been performed. In this study, we wish to resolve 3-amino-5-phenyl-1, 4-benzodiazepin-2-ones without derivatization on liquid chromatographic CSPs.…”

Preparation of Two New Diasteromeric Chiral Stationary Phases Based on (+)-(18-Crown-6)-2,3,11,12-tetracarboxylic Acid and (R)- or (S)-1-(1-Naphthyl)ethylamine and Chiral Tethering Group Effect on the Chiral Recognition

“…During the last several decades, quite effective CSPs have been developed by utilizing various chiral selectors. For example, polysaccharide derivatives [6,7], cyclodextrins [8], macrocyclic antibiotics [9,10], cyclofructans [11,12], Π-acidic or Π-basic aromatic chiral compounds [13,14], cinchona alkaloids [15,16], chiral ligand exchange materials [17,18] and chiral crown ethers [19][20][21] have been widely used as chiral selectors for the development of CSPs. Those chiral selectors are based on an assemblage of repeating or non-repeating chiral subunits playing together for chiral recognition or based on a single chiral unit.…”