Unambiguous Assignment of the 1H- and 13C-NMR Spectra of Propafenone and a Thiophene Analogue 英文参考文献.docVIP

Molecules 2001, 6, 796-802 molecules ISSN 1420-3049 Unambiguous Assignment of the 1H- and 13C-NMR Spectra of Propafenone and a Thiophene Analogue Wolfgang Holzer Institute of Pharmaceutical Chemistry, University of Vienna, Althanstrasse 14, A-1090 Vienna, Austria. Tel. (43)-1-4277-55123, Fax (43)-1-4277-9551, e-mail holzer@merian.pch.univie.ac.at Dedicated to Professor Wilhelm Fleischhacker on the occasion of his 70th birthday Received: 4 December 2001; in revised form 12 September 2001 / Accepted: 12 September 2001 / Published: 30 September 2001 Abstract: Full and unambiguous asssignment of all 1H- and 13C-NMR resonances of the free bases as well as the hydrochloride salts of the antiarrhythmic agent propafenone and a thiophene analogue in different solutions (DMSO-d6, CDCl3) is reported. Keywords: Propafenone, Antiarrhythmics, 1H-NMR, 13C-NMR Introduction Propafenone (1) is a class Ic antiarrhythmic drug with β-adrenoreceptor blocking and calcium antagonistic activity [1,2]. Moreover, 1 and related compounds have been identified to be highly effective modulators of multidrug resistance [3-5]. Although some NMR data of propafenone-like molecules have been reported [5-8] in most cases full assignments are missing and to the best of our knowledge no 13C-NMR data for the parent compound 1 have been published. Thus, the present communication deals with the completely assigned 1H- and 13C-NMR spectra of propafenone and its thiophene analogue 2 [9], obtained by combined application of one and two-dimensional standard NMR techniques.  Molecules 2001, 6 797 Results and Discussion Complete and unambiguous assignments of all proton and carbons resonances were achieved on the basis of chemical shift considerations, coupling information (APT [10] and gated decoupled 13C-NMR spectra), and NOE-difference [11], COSY45 [12], HMQC [13], and 1D-TOCSY [14] spectra as well as on long-range INEPT experiments