Enantioselective chromatography and molecular modeling of novel aryloxyaminopropan-2-ols with the alkyl carbamate function

• Published in: Chirality (New York, N.Y.) N.Y.), 2004, Vol.16 (3), p.139-146
• Main Authors: Navrátilová, Hana, Opatřilová, Radka, Kříž, Zdeněk, Koča, Jaroslav
• Format: Article
• Language: English
• Subjects: aryloxyaminopropanols; chiral recognition; Chiralcel OD-H; Chiralpak AD; enantioselective HPLC; low-energy conformers; molecular modeling
• ISSN: 0899-0042; 1520-636X
• DOI: 10.1002/chir.20008

A series of different racemic aryloxyaminopropan‐2‐ol derivatives 1a‐d–3a‐d with potential β‐adrenergic blocking effects related to propanolol 4 and atenolol 5 was resolved by HPLC using Chiralcel OD‐H and Chiralpak AD as chiral stationary phases. Mobile phases consisted of a hexane/alcohol (propan‐2‐ol or ethanol) mixture doped with a modifier (DEA or TFA). The retention behavior of the compounds depended on the position of the carbamate attached to the aryloxy moiety and on the length of the alkyl residue in the carbamate. Enantiomers of the title compounds were baseline separated with the separation factors α and resolutions Rs varying in the range of 1.34–4.55 and 1.50–10.65, respectively. The chromatographic systems developed can be used for the determination of the enantiomeric purity of the title compounds. Molecular modelling using empirical molecular mechanics and ab initio quantum chemistry methods provided low‐energy structures in which sites of potential interactions responsible for retention behavior and chiral recognition could be identified. Chirality 16:139–146, 2004. © 2004 Wiley‐Liss, Inc.