Tritium nuclear magnetic resonance spectroscopy of [Pyrrolidine-3H]bepridil

Abstract

Be p rid i I [ N-be nzy I -3i so b u toxy -Np he n y I -2 -( pyrrol id i n -1y I ) pro py la m i ne] t ri t ia ted i n the pyrro I id i ne ring by reduction of the 2,5-dihydropyrrol-I -yl analogue with tritium shows a complicated 'Hdecoupled 3H n.m.r. spectrum. With the aid of isotopic fractionation by h.p.1.c. this spectrum could be interpreted as a sum of the spectra of various mono-, di-, and tri-tritiated diastereoisomers. In the case of the (+)-(R)-isomer of bepridil the optical purity could be determined by 3H n.m.r. in the presence of Pirkle's alcohol. Tritium n.m.r. is the method of choice for the determination of the position and distribution of the tritium in labelled compounds.'.' The 'H decoupling which is usually applied simplifies the signals to singlets; for vicinal or geminal ditritiated compounds doublets are obtained which usually appear 0.05-0.1 p.p.m. upfield of the corresponding signals for the monotritiated compounds because of the isotope effect., Bepridil [N-benzyl-3-isobutoxy-N-phenyl-2-(pyrrolidin-1-y1)propylaminef (la) as its monohydrochloride monohydrate is a new anti-anginal drug with calcium antagonistic proper tie^.^ For biological and metabolical studies we synthesized this compound and ( +)-(R)-bepridil (lb) tritiated in the pyrrolidine ring. The n.m.r. spectra obtained for these compounds show very complex multiplets. The analysis of these spectra is described in this paper. * With 'H, no racemization was observed on reduction of compound (2b).

A Constellation of Deuterium‐Labeled Silanes as a Simple Mechanistic Probe not Requiring Absolute Configuration Determination

“…Inversion of the configuration at the silicon atom in both silanes 7 , that is, racemic 7 ‐ d 1 and meso ­ 7 ‐ d 2 , would produce the corresponding diastereomers. These diastereomeric pairs would be isochronic in their 1 H and 2 H NMR spectra yet present converse intensity patterns for the signals corresponding to their α positions 13. A useful property of silolanes is that their α protons are generally well resolved and unobscured in their NMR spectra.…”

“…Inversion of the configuration at the silicon atom in both silanes 7,t hat is,r acemic 7-d 1 and meso 7-d 2 , would produce the corresponding diastereomers.T hese diastereomeric pairs would be isochronic in their 1 Ha nd 2 HNMR spectra yet present converse intensity patterns for the signals corresponding to their a positions. [13] Au seful [*] Dr.T .F allon, [ property of silolanes is that their a protons are generally well resolved and unobscured in their NMR spectra. Importantly, the two diastereomers would have,toall practical intents and purposes,the same physical and chemical properties,with any potential difference in reactivity at the silicon atom silenced to the level of at ertiary isotope effect.…”

Eine Mischung deuteriummarkierter Silane als einfache mechanistische Sonde, die ohne Bestimmung von absoluten Konfigurationen auskommt

“…Inversion der Konfiguration am Siliciumatom in beiden Silolanen 7 , also racemischem 7 ‐ d 1 und meso ‐konfiguriertem 7 ‐ d 2 , führe zu den entsprechenden Diastereomeren. Diese Diastereomerenpaare wären isochron in ihren 1 H‐ und 2 H‐NMR‐Spektren und zwar mit umgekehrten Intensitätsmustern ihrer Signale in den α‐Positionen 13. Eine nützliche Eigenschaft der Silolane ist die gute und klare Auflösung der α‐Protonen in ihren NMR‐Spektren.…”