Pd‐ and Pt‐catalyzed H/D exchange methods and their application for internal MS standard preparation from a Sanofi‐Aventis perspective

Abstract

This review addresses method developments both homogeneous and heterogeneous Pd-and Pt-catalyzed exchange, including catalyst activation principles and recent practical applications together with example procedures. Specific requirements for isotopically labelled internal MS standard preparation are discussed from a Sanofi-Aventis perspective on recent examples.

Iridium-Catalysed ortho-Directed Deuterium Labelling of Aromatic Esters—An Experimental and Theoretical Study on Directing Group Chemoselectivity

“…In one particularly active branch of such labelling research, hydrogen isotope exchange (HIE) is employed to deliver either deuterium or radioactive tritium to pharmaceutical drug candidates in one synthetic step. As well as circumventing the requirement for isotopically-enriched starting materials in preparing tritiated drug candidates [1,5], HIE can also provide analogous deuterated compounds for use as internal standards for mass spectrometry [11,12], for kinetic isotope studies [13,14], and for the alteration of reaction pathways in total synthesis [15].…”

Frustrated Lewis pairs: A real alternative to deuteride/tritide reductions

“…The widespread use of isotopically labeled compounds have become well established and an essential tool for the identification of drug candidates; drugs; and drug metabolites in complex analytical and biochemical schemes of pharmaceutical, biological, and agrochemical research . The visualization of synthetized or isolated natural compounds is a fundamental aspect for studies of their action, affinity, and toxicity.…”

“…The widespread use of isotopically labeled compounds have become well established and an essential tool for the identification of drug candidates; drugs; and drug metabolites in complex analytical and biochemical schemes of pharmaceutical, biological, and agrochemical research. [1][2][3][4][5][6][7][8][9] The visualization of synthetized or isolated natural compounds is a fundamental aspect for studies of their action, affinity, and toxicity. Tritium, the most versatile radionuclide, readily labels small organic molecules of interest and is traditionally used in ligand-biological receptor-structure-activity studies or in administration, distribution, metabolism, and excretion (ADME) studies.…”

Deuterium‐ und tritiummarkierte Verbindungen: Anwendungen in den modernen Biowissenschaften

“…Das ist bei Tritium nicht der Fall, wenn-Wasserstoffisotope sind einzigartige Werkzeuge zur Identifizierung und Erforschung biologischer oder chemischer Vorgänge.W asserstoffisotopenmarkierungen erlauben den spurlosen und direkten Einbau einer zusätzlichen Masseneinheit oder eines radioaktiven Markers in ein organisches Molekül, und dies praktischo hne ¾nderungen der chemischen Struktur,d er physikalischen Eigenschaften oder der biologischen Aktivität. [12] Demgegenüber sind homogene,m etallkatalysierte HIE-Methoden sehr viel selektiver und erlauben den Einbau von Deuterium in spezifischen Positionen im Molekül, beispielsweise in Nachbarschaft zu einer dirigierenden Gruppe.Diese Methoden sind von besonderer Bedeutung fürd en Tr itiumeinbau durch H/T-Austausch. In diesem Aufsatz werden Fortschritte bei der Verwendung von Wasserstoffisotopen in den Biowissenschaften beschrieben.…”