1227703-21-0Relevant articles and documents
High throughput screening of monoamine oxidase (MAO-N-D5) substrate selectivity and rapid kinetic model generation
Rios-Solis,Mothia,Yi,Zhou,Micheletti,Lye
, p. 100 - 110 (2015)
Full kinetic models provide insight into enzyme mechanism and kinetics and also support bioconversion process design and feasibility assessment. Previously we have established automated microwell methods for rapid data collection and hybrid kinetic modelling techniques for quantification of kinetic constants. In this work these methods are applied to explore the substrate selectivity and kinetics of monoamine oxidase, MAO-N-D5, from Aspergillus niger. In particular we examine the MAO-N-D5 variant Ile246Met/Asn336Ser/Met348Lys/Thr384Asn to allow the oxidation of secondary amines Initial screening showed that MAO-N-D5 enabled the selective oxidation of secondary amines in 8 and 9 carbon rings, as well as primary ethyl and propyl amines attached to secondary amines of indolines and pyrrolidines. Subsequently we developed a first kinetic model for the MAO-N-D5 enzyme based on the ping-pong bi-bi mechanism (similar to that for the human MAO-A enzyme). The full set of kinetic parameters were then established for three MAO-N-D5 substrates namely; 3-azabicyclo[3,3,0]octane, 1-(2 amino ethyl) pyrrolidine and 3-(2,3-dihydro-1H-indole-1-yl)propan-1-amine. The models for each amine substrate showed excellent agreement with experimentally determined progress curves over a range of operating conditions. They indicated that in each case amine inhibition was the main determinant of overall reaction rate rather than oxygen or imine (product) inhibition. From the perspective of larger scale bioconversion process design, the models indicated the need for fed-batch addition of the amine substrate and to increase the dissolved oxygen levels in order to maximize bioconversion process productivity.
Asymmetric Synthesis of Tetracyclic Pyrroloindolines and Constrained Tryptamines by a Switchable Cascade Reaction
De Graaff, Corien,Bensch, Lisa,Boersma, Sjoerd J.,Cioc, R?zvan C.,Van Lint, Matthijs J.,Janssen, Elwin,Turner, Nicholas J.,Orru, Romano V. A.,Ruijter, Eelco
, p. 14133 - 14136 (2015)
The interrupted Fischer indole synthesis of arylhydrazines and biocatalytically generated chiral bicyclic imines selectively affords either tetracyclic pyrroloindolines or tricyclic tryptamine analogues depending on the reaction conditions. We demonstrate
Synthesis of Polycyclic Isoindolines via α-C-H/N-H Annulation of Alicyclic Amines
Paul, Anirudra,Vasseur, Camille,Daniel, Scott D.,Seidel, Daniel
supporting information, p. 1224 - 1227 (2022/02/09)
Relatively unstable cyclic imines, generated in situ from their corresponding alicyclic amines via oxidation of their lithium amides with simple ketone oxidants, engage aryllithium compounds containing a leaving group on an ortho-methylene functionality to provide polycyclic isoindolines in a single operation. The scope of this transformation includes pyrrolidine, piperidine, azepane, azocane, and piperazines.
Diversification of Unprotected Alicyclic Amines by C?H Bond Functionalization: Decarboxylative Alkylation of Transient Imines
Paul, Anirudra,Kim, Jae Hyun,Daniel, Scott D.,Seidel, Daniel
supporting information, p. 1625 - 1628 (2020/11/30)
Despite extensive efforts by many practitioners in the field, methods for the direct α-C?H bond functionalization of unprotected alicyclic amines remain rare. A new advance in this area utilizes N-lithiated alicyclic amines. These readily accessible intermediates are converted to transient imines through the action of a simple ketone oxidant, followed by alkylation with a β-ketoacid under mild conditions to provide valuable β-amino ketones with unprecedented ease. Regioselective α′-alkylation is achieved for substrates with existing α-substituents. The method is further applicable to the convenient one-pot synthesis of polycyclic dihydroquinolones through the incorporation of a SNAr step.
α,α′-C-H Bond Difunctionalization of Unprotected Alicyclic Amines
Valles, Daniel A.,Dutta, Subhradeep,Paul, Anirudra,Abboud, Khalil A.,Ghiviriga, Ion,Seidel, Daniel
supporting information, p. 6367 - 6371 (2021/08/18)
A simple one-pot procedure enables the sequential, regioselective, and diastereoselective introduction of the same or two different substituents to the α- and α′-positions of unprotected azacycles. Aryl, alkyl, and alkenyl substituents are introduced via their corresponding organolithium compounds. The scope of this transformation includes pyrrolidines, piperidines, azepanes, and piperazines.
