Semipreparative enantiomeric separation of a series of putative melatonin receptor agents using tri‐acetylcellulose as chiral stationary phase

Abstract

In order to obtain milligram amounts of the enantiomers of a series of compounds to be tested for binding to the melatonin binding site, a system for semipreparative enantiomeric separation was set up using tri-acetylcellulose as the chiral stationary phase. Interactions of this class of compounds with tri-acetylcellulose were examined on an analytical scale with a series of 20 compounds. Apparently, both steric and electrostatic interactions determine retention behavior on tri-acetylcellulose. Semipreparative separations were carried out for a subset of seven compounds. The purity of the first eluting enantiomer usually was around 99%, whereas the purity of the second eluting enantiomer was slightly less. The system described is easy to use and has the major advantage that a series of compounds can be separated with one technique. The purities obtained are sufficient for a first screen of their affinity.

Synthesis of Compounds as Melatonin Agonists and Antagonists

“…Indane and indene derivatives are effective cores for melatonin agonists [71][72][73][74]. 2-Aminoindans are readily available by the method of Cannon et al [75].…”

“…The tetralin and related systems prepared by Jansen et al [71] were resolved by HPLC using tri-acetylcellulose as the stationary phase. The R-tetralin 50 had been prepared by a stereoselective synthesis [111] and had a positive optical rotation.…”

Enantiomeric resolution of melatonin ligands receptors by liquid chromatography on amylose chiral stationary phases

“…It can be seen that decrease in the concentration polar modifier (ethanol: eluents A, B, G or 1-propanol: eluents C, D or 2-propanol: eluents E, F) in the mobile phase increases (k, Rs) parameters in a general manner both for 1 and 2 on Chiralpak AS [15,18]. This effect is illustrated in Figure 2 in the separation of compound la whose parameters (k, ct, Rs) are (1 95 [22,25].…”

“…to a significant reduction of retention times and retention factors (k), enantioselectivity factor (o 0 and resolution (Rs) [18,19]. On Chiralpak AS, for example, for la the parameters (k, o~, Rs) were (11.21, 1 31, 3.39); (3.…”

Synthesis, Enantiomeric Resolution, and Structure–Activity Relationship Study of a Series of 10,11‐Dihydro‐5H‐Dibenzo[a,d]cycloheptene MT2 Receptor Antagonists

“…This chiral phase was previously employed for the resolution of various racemates, especially aromatic pharmaceuticals, [19] and it was successfully used for the separation of enantiomeric mixture of MLT analogues. [20,21] Enantiomeric purity was verified and quantified using a prepacked Chiralcel OD-H column (cellulose tris-3,5-dimethylphenylcarbamate; …”