Chemo-biocatalytic one-pot two-step conversion of cyclic amine to lactam using whole cell monoamine oxidase

Abstract

BACKGROUND Most biocatalysts currently involved in one‐pot chemoenzymatic cascades are pure enzymes, while whole cells and crude enzyme extracts remain unexplored. This work aims to develop a chemo‐biocatalytic one‐pot two‐step system involving whole cell monoamine oxidase (MAO, EC 1.4.3.4) coupled with a Cu‐based oxidative system (CuI/H2O2) for the transformation of 1,2,3,4‐tetrahydroisoquinoline (THIQ) to 3,4‐dihydroisoquinolin‐1(2H)‐one (DHIO). RESULTS MAO‐N variants D9 and D11 were tested as whole cell and crude lysate biocatalysts for biological oxidation. Whole Escherichia coli OverExpress C43(DE3) cells expressing MAO‐N D9 showed the best performance (Vmax = 36.58 mmol L−1 h−1, KM = 8.124 mmol L−1, maximum specific productivity 89.3 μmol min−1 g−1DCW) and were employed in combination with CuI/H2O2 in a sequential one‐pot two‐step process. The biotransformation was scaled‐up to the initial volume of 25 mL and after triple THIQ feeding, 48.2 mmol L−1 of the intermediate 3,4‐dihydroisoquinoline (DHIQ) was obtained with a yield of 71.3%. Afterwards, chemical catalysts (1 mol% CuI and 10 eq. H2O2) were added to the biologically produced DHIQ, which was transformed to ∼30 mmol L−1 DHIO at 69.4% overall yield. CONCLUSION As MAO‐N variants have wide substrate specificity, this work broadens the portfolio of one‐pot chemoenzymatic processes employing whole cell biocatalysts, representing an alternative to using pure enzymes. © 2016 Society of Chemical Industry

Biocatalytic Oxidation Reactions: A Chemist's Perspective

“…Very recently, the further chemical oxidation of MAO‐N‐derived imines into lactams was demonstrated (Scheme b) . Similarly, Chen and co‐workers reported a whole‐cell oxidation of some amines to lactams …”

“…[133] Very recently,t he further chemical oxidation of MAO-N-derived imines into lactams was demonstrated (Scheme 36 b). [134] Similarly,C hen and co-workers reported awhole-cell oxidation of some amines to lactams. [135] An intramolecular version of the aforementioned electrophilic attack at in situ generated imines and iminium ions is catalysed by the so-called berberine bridging enzyme (BBE).…”

Biokatalytische Oxidationsreaktionen – aus der Sicht eines Chemikers

“…Kürzlich konnte die Oxidation von Aminen zu Lactamen durch Kombination von MAO‐N mit einer Cu‐katalysierten Oxidation des resultierenden Imins gezeigt werden (Abbildung b) . Eine Ganzzellvariante wurde von Chen und Mitarbeitern publiziert …”

Chemo‐Enzymatic One‐Pot Two‐Step Functionalization of 1,2,3,4‐Tetrahydroisoquinolines by Monoamine Oxidase‐Ugi‐Joullié Reaction Sequence

“…In contrast, one-pot functionalization of cyclic amines via imines was achieved with cyanide [22,28] and pyrroles [29] as nucleophiles, as well as via gold-catalyzed alkynylation [30] and metal-or enzyme-catalyzed oxidation to the corresponding lactams (Figure 1). [31,32] We aimed to apply a similar amine oxidation-imine addition sequence to functionalize 1,2,3,4-tetrahydroisoquinolines (THIQs) which are prominent scaffolds in medicinal chemistry and in commercial drugs, e. g. quinapril, solifenacin, lifitegrast. [33,34] They are also abundant in nature.…”