Čes. slov. farm. 2021, 70(2):51-58 | DOI: 10.5817/CSF2021-2-51

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

Ružena Čižmáriková, Ladislav Habala^*, Jindra Valentová, Dana Šmátralová

Farmaceutická fakulta UK, Katedra chemickej teórie liečiv, Bratislava, SR

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

Received: February 26, 2021; Accepted: April 9, 2021; Published: February 1, 2021  Show citation