Enantiokonvergente biokatalytische Redoxisomerisierung

Abstract

Alkoholdehydrogenasen dienen als effektive Katalysatoren in der Herstellung optisch aktiver g-Hydroxy-d-lactone auf Grundlage einer enantiokonvergenten dynamischen Redoxisomerisierung von einfach zugänglichen, racemischen Achmatowicz-Pyranonen. Durchd ie Nachahmung der übergangsmetallvermittelten "Borrowing-hydrogen"-Methodik zur Überführung von Hydridspezies innerhalb heterocyclischer Gerüste erlaubt diese chemoinspirierte,j edochv ollständig biokatalysierte Interpretation das bestehende Syntheserepertoire von Enzymen effektiv zu erweitern und bietet hierdurch neue Mçglichkeiten in der Konstruktion von Multienzymkaskaden sowiei mDesign maßgeschneiderter Zellfabriken. Schema 1. a) Klassisches "borrowing hydrogen": Iridium-vermittelte Redoxisomerisierung von Achmatowicz-Pyranonen.b )Nicotinamid-abhängige Dehydrogenase als difunktionaler enantioselektiver Isomerisierungskatalysator.

Methanol-Driven Oxidative Rearrangement of Biogenic Furans – Enzyme Cascades vs. Photobiocatalysis

“…As all Achmatowicz reactions provide densely functionalized pyranone products ( 2 ) that carry multiple reactive groups, very high yields pose a general challenge for any methodology aiming for selective furan oxidation protocols. One way to address this issue specifically within enzymatic catalysis is the creation of biocatalyic cascades where the pyranone is further telescoped in situ to a more stable final product ( Liu et al, 2018 ). Nevertheless, to shed light on the synthetic value of the different methods beyond the initial catalytic optimization, preparative yields of the product 2a need to be considered.…”

“…Here, the oxygen-transfer biocatalyst is supplemented by glucose oxidase (GOx) to provide the necessary hydrogen peroxide via reduction of air. Although this protocol has been proven to be highly effective, and has been implemented into synthetic applications ( Blume et al, 2016 ) and biocatalytic cascades ( Liu et al, 2018 ), we have pursued the search for alternative aerobic activation routes in order to substitute the glucose, on one side to create complementary sacrificial agents for the design of more complex biocascades, but also due to the somewhat poor atom-economy of the glucose. Among the various potential reductants to drive peroxidase-catalyzed reactions, methanol stands out as most attractive reagent as it offers the highest hydrogen density of common, enzyme-compatible small molecules and as it can theoretically provide up to three equivalents of hydrogen peroxide when oxidized all the way to carbon dioxide ( Kara et al, 2015 ).…”