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Defining Pathways of Anaerobic Alkane Oxidation: Synthesis of Enantiomers of 4-Methylalkanoic Acids and (2-Methylalkyl)malonic Acids

Lookup NU author(s): Dr Marta Drozdowska, Jay Tromans, Dr Bian Zhang, Professor Bernard Golding

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

© 2021 The Authors. ChemistrySelect published by Wiley-VCH GmbHThe coenzyme A (CoA) esters of 4-methylalkanoic acids are pivotal intermediates in metabolism of alkanes by anaerobic bacteria found in O2-deprived environments. A generic method for synthesis of either (R)- or (S)-acid in high enantiomeric purity from enantiomers of methyl 3-hydroxy-2-methylpropionate is described for (R)- and (S)-4-methyloctanoic acid and (R)-4-methyldodecanoic acid. In a typical procedure silyl-protection of methyl (S)-3-hydroxy-2-methylpropionate was followed by reduction of the ester to a primary alcohol, which was tosylated. Cu(I)-catalysed cross-coupling of the tosylate with propylmagnesium chloride followed by deprotection, tosylation and base-induced reaction with di-t-butyl malonate, gave di-t-butyl (R)-(2-methylhexyl)malonate. Microwave heating of the diester in 2,2,2-trifluoroethanol gave a 42 % overall yield of (R)-4-methyloctanoic acid, which was shown to be the enantiomer derived by metabolism of hexane by proteobacterium Aromatoleum sp. HxN1. Deprotection of the diester with trifluoroacetic acid gave (R)-2-(2-methylhexyl)malonic acid, which is the biological precursor of (R)-4-methyloctanoic acid (via CoA esters).


Publication metadata

Author(s): Drozdowska M, Tromans J, Zhang B, Jarling R, Wilkes H, Golding BT

Publication type: Article

Publication status: Published

Journal: ChemistrySelect

Year: 2021

Volume: 6

Issue: 16

Pages: 3976-3981

Online publication date: 06/05/2021

Acceptance date: 16/04/2021

Date deposited: 07/03/2022

ISSN (electronic): 2365-6549

Publisher: John Wiley and Sons Inc

URL: https://doi.org/10.1002/slct.202100415

DOI: 10.1002/slct.202100415


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