Preparation of 2R, 3S, 2′R-nadolol enantiomer using S-(-)-menthyl chloroformate as a chiral derivatizing reagent

Abstract

Stereoisomers of nadolol were derivatized with S-(-)-menthyl chloroformate((-)-MCF) forming their diastereomers, RSR-nadolol-(-)-MCF, SRS-nadolol-(-)-MCF, RRS-nadolol-(-)-MCF and SSRnadolol-(-)-MCF. Diastereomeric mixture were then chromatographically resolved by preparative HPLC (JAIGEL-ODS-BP-L, 500 × 25 mm column) eluted with methanol-water (84:16, v/v) at flow rate 2.5 mL/min. RSR-nadolol-(-)-MCF diastereomer was hydrolyzed with 5% LiOH at 80°C for 48 h, and the decomposed mixture was further purified by semi-preparative HPLC. The purity and final yield of RSR-nadolol were 99.97% and 12.95%, respectively.

Separation of nadolol racemates by high pH reversed-phase preparative chromatography

“…The first work of preparative production of the RSR-nadolol pure stereoisomer was published in 2010 by Sung and co-authors. However, the method was based in the resolution via diastereomeric salt formation, followed by preparative HPLC using a JAIGEL-ODS-BP-L 25x500 mm column and methanol:water (84:16) as mobile phase [32]. Wang and Ching [33][34][35] published the first studies concerning the application of SMB technology to the separation of nadolol stereoisomers.…”

Validação dos sistemas computadorizados empregados na determinação dos enantiômeros do nadolol e dos homólogos da ivermectina e da abamectina

“…Estrutura química do nadolol (UNITED STATES PHARMACOPEIA, 2016) Estrutura química dos enantiômeros do nadolol(SUNG, 2010) …”