Synthesis and enantioseparation of derivatives of propranolol

R. Čižmáriková 1 , S. Chudáčiková 1 , J. Valentová 1 , and A. Némethy 1
  • 1 Faculty of Pharmacy, Department of Chemical Theory of Drugs, Comenius University in Bratislava

Synthesis and enantioseparation of derivatives of propranolol

Propranolol is one of the first prepared and in therapeutic praxis used beta- adrenolytics. In this paper novel derivatives of propranolol with cyclohexylamino and pyrrolidin-1-yl groups in hydrophilic part were prepared. HPLC-enantioseparation propranolol (as reference compound) and of the prepared derivatives has been achieved using a Chiralpak AD CSP based on the amylose tris (3,5-dimethylphenylcarbamate).(R)-enantiomer of the propranolol was prepared by stereoselective synthesis using Jacobsen catalyst.

If the inline PDF is not rendering correctly, you can download the PDF file here.

  • Aboul-Enein HY, Bakr SA. Enantiomeric resolution of propranolol and analogs on two cellulose (Chiracel of and OC) and one amylose (Chiracel AD) chiral stationary phases. J Liq Chrom & Relat Techn. 1998;8:1137-1145.

  • Bevinakatti, HS, Banerji AA. Practical chemoenzymic synthesis of both enantiomers of propranolol. J Org Chem. 1991;56:5372-5375.

  • Bojarski J. Stereoselective chromatography of cardiovascular drugs: an update. J Biochem Biophys Methods. 2002;54:197-220.

  • Bruchatá K, Čižmáriková R, Hroboňová K, Lehotay J, Kyselová Z. Synthesis and study of enantioseparation of some potencial β-blockers of aryloxyaminopropanol type by HPLC using macrocyclic antibiotics as chiral selector. Acta Fac Pharm Univ Comen. 2006;53:68-75.

  • Crowter AF, Smith LH. Beta-adrenergic blocking agents II. Propranolol and related 3-amino-1-naphthoxy-2-propanols. J Med Chem. 1968;11:1009-1013.

  • Čižmáriková R, Hroboňová K, Lehotay J, Račanská E, Bruchatá K. Preparation, pharmacological activity and enantioseparation of [3-cyclopentyloxymethyl)-4-(2-hydroxy-3-isopropylaminopropoxy)phenyl]ethanone as potential β-blocker. Acta Fac Pharm Univ Comen. 2005;52:79-88.

  • Čižmáriková R. β-Adrenergic receptor blockers-the group of chiral drugs: Different effect of individual enantiomers (in Slovak). Čes slov Farm. 2002;51:121-128.

  • Eshghi H, Porkar YH. A facile synthesis of (S)-(-)propranolol. J Sci I R Iran. 2003;14:17-19.

  • Fischer W. Anticonvulsant profile and mechanism of action of propranolol and its two enantiomers. Seizure. 2002;11:285-302.

  • Florenz J, Pomor JL, Malpartida F. Beta-adrenergic blockade and antiarrhythmic activity of (-) and (+) propranolol. Rev Espan Fisiol. 1969;25:287-292.

  • Lohman D, Lehmann D, Morgenstern E, Faust G. Synthese and antikonvulsive Wirkung von Propranolol Derivaten mit tertiärem Stickstoffatom. Pharmazie. 1990;45:401-403.

  • Mathett MW, Branch SK, Jefferies TM. Polar organic chiral separation of propranolol and analogues using a β-cyclodextrin bonded stationary phase. Chirality. 1996;8:126-130.

  • Ram N, Heilman RD, Greenslade FC. Antihypertensive activity of a propranolol analog (ORF 12, 592) in rodents. Arch. Int Pharmacodyn Ther. 1976;224:102-108.

  • Schaus ES, Brandes BD, Larrow JF, Tokunaga M, Hansen KB, Gould AF, Furrow MF, Jacobsen EN. Highly selective hydrolytic kinetic resolution of terminal epoxides catalyzed by chiral (salen) Co III comlexes. Practical synthesis of enantioenriched terminal epoxides and 1,2-diols. J Am Chem Soc. 2002;124:1307-1315.

  • Valentová J, Čižmåiková R, Bui TTT, Drake AF, Hull AJ. Enantiomeric resolution of novel aryloxyaminopropanol derivatives with β-adrenoceptor antagonist activity on a derivatised amylose chiral stationary. Chromatographia. 2003;11/12:733-740.

OPEN ACCESS

Journal + Issues

Search