N-Phenylputrescine (NPP): a natural product inspired amine donor for biocatalysis

Catherine A Mckenna,Irene De Silvestro,Andrew L Lawrence,Dominic J Campopiano,Mária Štiblariková

doi:10.1039/d1gc02387j

Catherine A Mckenna, Irene De Silvestro + Show 3 more

Open Access

https://doi.org/10.1039/d1gc02387j

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Abstract

A novel amine donor has been shown to be suitable for the transaminase-catalysed conversion of aldehydes and ketones to various amines across a range of conditions.

Highlights

An adaptation of the L-amino acid oxidase (L-AAO) and horse radish peroxidase (HRP) coupled colourimetric assay was used to investigate the kinetics of L-alanine formation.[40,41]
To further explore the effectiveness of NPP 9 as an amine donor in comparison to i-PrNH2, we investigated the synthesis of chiral amines from more challenging substrates such as p-methoxy acetophenone 15 (Fig. 5a) and 1-indanone 17 (Fig. 5b)
The continued demand for a universal amine donor for biocatalytic transaminations prompted us to explore how nature achieves the biosynthesis of complex natural products via TA-mediated pathways

Summary

Introduction

The need to develop more sustainable manufacturing processes in the pharmaceutical, agrochemical, and other fine-chemical industries has led to an increased interest in biocatalytic methods.[1,2,3,4,5,6] By using biocatalysts, enantiopure compounds can often be produced in high yield under very mild aqueous reaction conditions, but they can suffer from several practical limitations and drawbacks.[7,8] For example, transaminases (TAs or ATAs) provide an environmentally friendly alternative to traditional transition-metal catalysed methods for the synthesis of chiral amines, which are ubiquitous building blocks in the pharmaceutical and agrochemical industries, and find wide application as chiral auxiliaries, catalysts, ligands, and resolving agents (Fig. 1).[9,10] TA-mediated transamination reactions often suffer from unfavourable reaction equilibria, an issue that can critically limit many biocatalytic methods.[11]. Pavlidis and co-workers stated “...designing industrial processes with these enzymes [TAs] is still challenging, due to the fact that a universal and discernible amine donor system has not been developed”.26 We took inspiration for the design of a new amine donor from the proposed biosynthetic pathway of the plant-derived dipyrroloquinoline alkaloids, incargranine B (7) and seneciopiperidine (8) (Fig. 2c).[36] TA-mediated oxidative deamination of an N-arylputrescine 4 is proposed to give an enamine 6 and an iminium ion 5 that react together through an irreversible Povarov reaction to give the dipyrroloquinoline framework.

Results

Conclusion