Bioinspired Synthesis of Pinoxaden Metabolites Using a Site-Selective C–H Oxidation Strategy

Abstract

A bioinspired synthesis of Pinoxaden metabolites 2–5 is described herein. A site-selective C–H oxidation strategy validated by density functional theory (DFT) calculations was devised for preparing metabolites 2–4. Oxidation of the benzylic C–H bond in tertiary alcohol 7 using K2S2O8 and catalytic AgNO3 formed the desired metabolite 2 that enabled access to metabolites 3 and 4 in a single step. Unlike most metal/persulfate-catalyzed transformations reported for the C–C and C–O bond formation reactions wherein the metal acts as a catalyst, we propose that Ag­(I)/K2S2O8 plays the role of an initiator in the oxidation of intermediate 7 to 2. Metabolite 2 was subjected to a ruthenium tetroxide-mediated C–H oxidation to form metabolites 3 and 4 as a mixture that were purified to isolate pure standards of these metabolites. Metabolite 5 was synthesized from readily available advanced intermediate 9 via a House–Meinwald-type rearrangement in one step using a base

The Future of (Radio)‐Labeled Compounds in Research and Development within the Life Science Industry

“…When these need to be radiolabeled and the labelling position is identified, further considerations as to the availability of labeled starting materials often dictates the route(s) chosen. [99] As mentioned earlier detection of the parent and the metabolites are typically done using LC with radioactive detection in conjunction with another technique, usually liquid scintillation counting (LSC) or quantitative TLC. Quantitative TLC involves the use of beta-phosphor imaging then confirming with scraping and LSC of each of the areas of interest.…”

Die Zukunft (Radio‐)‐isotopenmarkierter Verbindungen in Forschung und Entwicklung der modernen Lebenswissenschaften

“…Wenn diese Metabolite radioaktiv markiert werden müssen und die Position der Markierung festgelegt ist, bestimmt oft die Verfügbarkeit markierter Ausgangsstoffe die gewählte(n) Route(n) (Schema 6). [99] Wie bereits erwähnt, erfolgt der Nachweis der Ausgangssubstanz und der Metaboliten in der Regel durch LC mit radioaktivem Nachweis in Verbindung mit einer anderen Technik, in der Regel Flüssigszintillationszählung (LSC) oder quantitative TLC. Bei der quantitativen TLC wird ein Beta-Phosphor-Imaging verwendet, das dann durch Auskratzen und LSC der einzelnen interessierenden Bereiche bestätigt wird.…”

Kilogram synthesis of pinoxaden

“…Pinoxaden (Axial, 1, Scheme 1), developed by Syngenta Crop Protection Ltd, is a new type of phenyl pyrazoline herbicide, which belongs to the phenylpyrazole chemical family of ACCase inhibitors [1]. It is used as a postemergence herbicide for controlling various grass weed species in wheat and barley crops, which demonstrates broadspectrum activity against a range of grass weeds including wild oats, green foxtail, barnyard grass, volunteer oats, and so on [2,3].…”