Enantioseparation of 5-chloro-2-(2-(3,4-dihydroisoquinoline-2(1H)-yl)ethyl)-2-methyl-2,3-dihydro-1H-inden-1-one (SYA 40247), a high affinity 5-HT7 receptor ligand, by HPLC-PDA using amylose tris-(3, 5- dimethylphenylcarbamate) as a chiral stationary phase

• Published in: Biomedical chromatography Vol. 33; no. 9; p. e4565
• Main Authors: Onyameh, Edem K., Bricker, Barbara A., Ofori, Edward, Ablordeppey, Seth Y.
• Format: Journal Article
• Language: English
• Published: 11-07-2019
• ISSN: 0269-3879; 1099-0801
• DOI: 10.1002/bmc.4565

In a previous structure activity relationship studies to identify new and
selective 5-HT
7
receptor (5-HT
7
R) ligands, we have
identified the chiral compound,
5-chloro-2-(2-(3,4-dihydroisoquinoline-2(1
H
)-yl)ethyl)-2-methyl-2,3-dihydro-1
H
-inden-1-one
(SYA 40247), with high affinity binding to the 5-HT
7
R. Thus, it was
of interest to separate the enantiomers in order to evaluate their affinity at
the 5-HT
7
R. To achieve this separation, a normal phase analytical
method using HPLC-PDA and a 4.6 mm x 250 mm Chiralpak AD-H column was first
developed. Optimized isocratic conditions of 1.00 mL/min 95:5:0.1 v/v/v
hexane:ethanol:diethylamine and a 254 nm analysis wavelength yielded a 6.07 min
baseline separation. The method was scaled up to a 10 mm x 250 mm Chiralpak AD-H
column, allowing 3 mg of racemate to be separated with a single injection, and 6
mg for an overlapping double injection in the same run. The separated
enantiomers were reinjected into the analytical HPLC system, peak identities
confirmed by retention time and PDA UV spectra, and the enantiomeric purities
determined to be 100% for Peak 1 and 100% for Peak 2. A JASCO P-1020 polarimeter
was used to determine the specific rotation [α] of the enantiomers Peak 1
and Peak 2 which were −86.2 and +93.3 (deg·mL) /(g·dm)
respectively. No racemization was observed, and the enantiomeric purity remained
at 100% for each peak.