Synthesis and HPLC enantioseparation of novel derivatives of 3-alkoxy-4-hydroxyphenylalkanones of a potential α/β-blocker type

Czech version

Authors: Ružena Čižmáriková; Ladislav Habala; Jindra Valentová; Dana Šmátralová
Authors‘ workplace: Katedra chemickej teórie liečiv, Farmaceutická fakulta UK, Bratislava, SR
Published in: Čes. slov. Farm., 2021; 70, 51-58
Category: Original Article
doi: https://doi.org/10.5817/CSF2021-2-51

Overview

The present paper reports the synthesis of a series of seven compounds with a hetero aminopropanol chain. The compounds were prepared by the conversion of 3-alkoxy-4-hydroxyphenyl alkanones with 2-chloromethyl oxirane and subsequent reaction of the products with heterocyclic amines (pyrrolidine, azepane, 4-methylpiperazine and 2-methoxyphenyl piperazine). The target compounds were synthesized in the form of racemates. The purity of the products was confirmed by thin layer chromatography and their IR, UV-VIS and ¹H-NMR spectra were recorded. Enantioseparation of the racemic products was accomplished by HPLC on a Chiralpak AD chiral chromatographic column with tris(3,5-dimethylphenyl)carbamate as the chiral selector. The efficiency of enantioseparation was determined in relation to the composition of the mobile phase (hexane : ethanol : methanol : ethylethanamine) and to the structure of the prepared compounds. Baseline separation was achieved with all compounds using mobile phases A (78 : 11 : 11 : 0,1 v/v/v/v) and B (80 : 10 : 10 : 0,1 v/v/v/v),
with selectivity factor ranging from 1.07 to 1.42 and resolution from 0.76 to 5.47. The mobile phase containing a higher amount of hexane did not allow for successful enantioseparation of the piperazine derivatives.

Keywords:

3-alkoxy-4-hydroxyphenylalkanones – beta-blockers – enantioseparation – HPLC – Chiralpak AD

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Czech and Slovak Pharmacy

2021 Issue 2