Biocatalytic N-Alkylation of Amines Using Either Primary Alcohols or Carboxylic Acids via Reductive Aminase Cascades

Jeremy I. Ramsden; Rachel S. Heath; Sasha R. Derrington; Sarah L. Montgomery; Juan Mangas-Sanchez; Keith R. Mulholland; Nicholas J. Turner

doi:10.1021/jacs.8b11561

Biocatalytic N-Alkylation of Amines Using Either Primary Alcohols or Carboxylic Acids via Reductive Aminase Cascades

Jeremy I. Ramsden, Rachel S. Heath, Sasha R. Derrington, Sarah L. Montgomery, Juan Mangas-Sanchez, Keith R. Mulholland, Nicholas J. Turner^*

^*Corresponding author for this work

AstraZeneca

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Abstract

The alkylation of amines with either alcohols or carboxylic acids represents a mild and safe alternative to the use of genotoxic alkyl halides and sulfonate esters. Here we report two complementary one-pot systems in which the reductive aminase (RedAm) from Aspergillus oryzae is combined with either (i) a 1° alcohol/alcohol oxidase (AO) or (ii) carboxylic acid/carboxylic acid reductase (CAR) to affect N-alkylation reactions. The application of both approaches has been exemplified with respect to substrate scope and also preparative scale synthesis. These new biocatalytic methods address issues facing alternative traditional synthetic protocols such as harsh conditions, overalkylation and complicated workup procedures.

Original language	English
Journal	Journal of the American Chemical Society
Early online date	2 Jan 2019
DOIs	https://doi.org/10.1021/jacs.8b11561
Publication status	Published - 23 Jan 2019

Research Beacons, Institutes and Platforms

Manchester Institute of Biotechnology

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10.1021/jacs.8b11561

Ramsden et al manuscript 29 Nov 2018Accepted author manuscript, 939 KB

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title = "Biocatalytic N-Alkylation of Amines Using Either Primary Alcohols or Carboxylic Acids via Reductive Aminase Cascades",

abstract = "The alkylation of amines with either alcohols or carboxylic acids represents a mild and safe alternative to the use of genotoxic alkyl halides and sulfonate esters. Here we report two complementary one-pot systems in which the reductive aminase (RedAm) from Aspergillus oryzae is combined with either (i) a 1° alcohol/alcohol oxidase (AO) or (ii) carboxylic acid/carboxylic acid reductase (CAR) to affect N-alkylation reactions. The application of both approaches has been exemplified with respect to substrate scope and also preparative scale synthesis. These new biocatalytic methods address issues facing alternative traditional synthetic protocols such as harsh conditions, overalkylation and complicated workup procedures.",

author = "Ramsden, \{Jeremy I.\} and Heath, \{Rachel S.\} and Derrington, \{Sasha R.\} and Montgomery, \{Sarah L.\} and Juan Mangas-Sanchez and Mulholland, \{Keith R.\} and Turner, \{Nicholas J.\}",

year = "2019",

month = jan,

day = "23",

doi = "10.1021/jacs.8b11561",

language = "English",

journal = "Journal of the American Chemical Society",

issn = "0002-7863",

publisher = "American Chemical Society",

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T1 - Biocatalytic N-Alkylation of Amines Using Either Primary Alcohols or Carboxylic Acids via Reductive Aminase Cascades

AU - Ramsden, Jeremy I.

AU - Heath, Rachel S.

AU - Derrington, Sasha R.

AU - Montgomery, Sarah L.

AU - Mangas-Sanchez, Juan

AU - Mulholland, Keith R.

AU - Turner, Nicholas J.

PY - 2019/1/23

Y1 - 2019/1/23

N2 - The alkylation of amines with either alcohols or carboxylic acids represents a mild and safe alternative to the use of genotoxic alkyl halides and sulfonate esters. Here we report two complementary one-pot systems in which the reductive aminase (RedAm) from Aspergillus oryzae is combined with either (i) a 1° alcohol/alcohol oxidase (AO) or (ii) carboxylic acid/carboxylic acid reductase (CAR) to affect N-alkylation reactions. The application of both approaches has been exemplified with respect to substrate scope and also preparative scale synthesis. These new biocatalytic methods address issues facing alternative traditional synthetic protocols such as harsh conditions, overalkylation and complicated workup procedures.

AB - The alkylation of amines with either alcohols or carboxylic acids represents a mild and safe alternative to the use of genotoxic alkyl halides and sulfonate esters. Here we report two complementary one-pot systems in which the reductive aminase (RedAm) from Aspergillus oryzae is combined with either (i) a 1° alcohol/alcohol oxidase (AO) or (ii) carboxylic acid/carboxylic acid reductase (CAR) to affect N-alkylation reactions. The application of both approaches has been exemplified with respect to substrate scope and also preparative scale synthesis. These new biocatalytic methods address issues facing alternative traditional synthetic protocols such as harsh conditions, overalkylation and complicated workup procedures.

UR - https://www.scopus.com/pages/publications/85060003715

U2 - 10.1021/jacs.8b11561

DO - 10.1021/jacs.8b11561

M3 - Article

AN - SCOPUS:85060003715

SN - 0002-7863

JO - Journal of the American Chemical Society

JF - Journal of the American Chemical Society

ER -

Biocatalytic N-Alkylation of Amines Using Either Primary Alcohols or Carboxylic Acids via Reductive Aminase Cascades

Abstract

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Driving the industrial biotechnology revolution: cheaper and more sustainable chemical manufacturing through enzyme discovery, engineering and scale-up

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Biocatalytic N-Alkylation of Amines Using Either Primary Alcohols or Carboxylic Acids via Reductive Aminase Cascades

Abstract

Research Beacons, Institutes and Platforms

Access to Document

Other files and links

Fingerprint

Impacts

Driving the industrial biotechnology revolution: cheaper and more sustainable chemical manufacturing through enzyme discovery, engineering and scale-up

Cite this