Synthesis of new C3 symmetric amino acid‐ and aminoalcohol‐containing chiral stationary phases and application to HPLC enantioseparations

Abstract

We recently reported a new C3-symmetric (R)-phenylglycinol N-1,3,5-benzenetricarboxylic acid-derived chiral high-performance liquid chromatography (HPLC) stationary phase (CSP 1) that demonstrated better results as compared to a previously described N-3,5-dintrobenzoyl (DNB) (R)-phenylglycinol-derived CSP. Over a decade ago, (S)-leucinol, (R)-phenylglycine, and (S)-leucine derivatives were used as the starting materials of 3,5-DNB-based Pirkle-type CSPs for chiral separation. In this study, three new C3-symmetric CSPs (CSP 2, 3, and 4) were prepared by combining the ideas and results mentioned above. Here we describe the synthetic procedures and applications of the new C3-symmetric CSPs (CSP 2-CSP 4).

Ultrasound‐Controlled Chiral Separation of Four Amino Acids and 2,2,2‐Trifluoro‐1‐(9‐anthryl)ethanol

“…Flow rate; 1.2 mL/min, detection; 254 nm, mobile phase; 10% IPA in hexane, column; C 3 symmetric CSP …”

“…The chiral columns used are as follows, with an inner diameter of 4.6 mm and length of 25 cm: cellulose column, Lux 5μm cellulose‐1, Phenomenex Inc., Torrance, CA, USA; crown ether column; ChiroSil ® RCA(+), Regis Technologies, Inc., Grove, IL, USA. C 3 symmetric CSP; home‐made CSP . All the samples used in this experiment were purchased from Sigma Aldrich Inc. (Milwaukee, WI, USA).…”

“…Methionine : column; Chirosil ® RCA(+), flow rate; 1.0 mL/min, detection; 210 nm; mobile phase; methanol/water (45:55) + 10 mM acetic acid. TFAE : column; C 3 symmetric CSP, flow rate; 1.2 mL/min, detection; 254 nm, mobile phase; 10% IPA in hexane.…”

Determination of Enantiomeric Purity for Chiral π‐Basic Aromatic Alcohols Chiral Samples by 1H NMR Spectroscopy

“…Sel 1 employed in the NMR study was DNB‐phenyl glycinol, which is used as an intermediate in the synthesis of CSP 1 . Sel 2, which was also used as an intermediate in the synthesis of CSP 1, was formed by binding 3‐(triethoxy)propyl isocyanate to Sel 1 . Sel 3 was prepared by synthesizing 2‐methyl‐1‐butanol in calixarene, as follows .…”

“…However, even if the racemic mixture is separated from the selected column, without high selectivity, complete baseline separation is not quite achieved and the accuracy of the enantiomeric purity decreases. In a previous study, the chiral stationary phase (CSP), N ‐3,5‐dinitrobenzoyl(DNB)‐(R)‐phenylglycinol derived CSP (CSP 1), one of the representative amino alcohol‐derived Pirkle‐type CSP, was effectively used for π‐acidic, π‐basic, and aromatic chiral samples . 2,2,2‐Trifluoro‐1‐(9‐anthryl)ethanol (TFAE, S1) was separated from CSP 1 with an α value (separation factor) of about 1.16, but poor baseline separation (Rs: 0.82).…”