Metabolism mimicry: an electrosynthetic method for the selective deethylation of tertiary benzamides

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Metabolism mimicry : an electrosynthetic method for the selective deethylation of tertiary benzamides. / Bal, Mandeep; Banks, Craig; Jones, Alan M.

In: ChemElectroChem, Vol. 6, No. 16, 16.08.2019, p. 4284-4291.

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@article{4b300c3170ee4f79a354a45826f57354,
title = "Metabolism mimicry: an electrosynthetic method for the selective deethylation of tertiary benzamides",
abstract = "The electrosynthetic deethylation of tertiary amides, commonly encountered moieties in pharmaceuticals and agrochemicals, is an analogue of the function of cytochrome P450 enzymes, a major oxidant metabolic pathway for xenobiotics. The ability to tractably synthesise, in a late‐stage manner, drug metabolites from the parent drug is currently unsolved. We report the first study, mechanistic rationale, and synthetic scope of an undivided controlled current electrosynthetic method that selectively mono deethylates tertiary amides without over‐reaction. An optimisation survey found that changing the electron input from controlled voltage to controlled current conditions led to deethylation rather than the expected dehydrogenative coupling. The scope and limitations of the method were interrogated with 14 examples with the parent benzamide reaction optimised (86 % yield) and the scalable production of the major human metabolite of the insect repellent DEET was achieved from the parent molecule in one step.",
keywords = "deethylation, dealkylation, electrosynthesis, tertiary amide, metabolites",
author = "Mandeep Bal and Craig Banks and Jones, {Alan M}",
year = "2019",
month = aug,
day = "16",
doi = "10.1002/celc.201900028",
language = "English",
volume = "6",
pages = "4284--4291",
journal = "ChemElectroChem",
issn = "2196-0216",
publisher = "Wiley",
number = "16",

}

RIS

TY - JOUR

T1 - Metabolism mimicry

T2 - an electrosynthetic method for the selective deethylation of tertiary benzamides

AU - Bal, Mandeep

AU - Banks, Craig

AU - Jones, Alan M

PY - 2019/8/16

Y1 - 2019/8/16

N2 - The electrosynthetic deethylation of tertiary amides, commonly encountered moieties in pharmaceuticals and agrochemicals, is an analogue of the function of cytochrome P450 enzymes, a major oxidant metabolic pathway for xenobiotics. The ability to tractably synthesise, in a late‐stage manner, drug metabolites from the parent drug is currently unsolved. We report the first study, mechanistic rationale, and synthetic scope of an undivided controlled current electrosynthetic method that selectively mono deethylates tertiary amides without over‐reaction. An optimisation survey found that changing the electron input from controlled voltage to controlled current conditions led to deethylation rather than the expected dehydrogenative coupling. The scope and limitations of the method were interrogated with 14 examples with the parent benzamide reaction optimised (86 % yield) and the scalable production of the major human metabolite of the insect repellent DEET was achieved from the parent molecule in one step.

AB - The electrosynthetic deethylation of tertiary amides, commonly encountered moieties in pharmaceuticals and agrochemicals, is an analogue of the function of cytochrome P450 enzymes, a major oxidant metabolic pathway for xenobiotics. The ability to tractably synthesise, in a late‐stage manner, drug metabolites from the parent drug is currently unsolved. We report the first study, mechanistic rationale, and synthetic scope of an undivided controlled current electrosynthetic method that selectively mono deethylates tertiary amides without over‐reaction. An optimisation survey found that changing the electron input from controlled voltage to controlled current conditions led to deethylation rather than the expected dehydrogenative coupling. The scope and limitations of the method were interrogated with 14 examples with the parent benzamide reaction optimised (86 % yield) and the scalable production of the major human metabolite of the insect repellent DEET was achieved from the parent molecule in one step.

KW - deethylation

KW - dealkylation

KW - electrosynthesis

KW - tertiary amide

KW - metabolites

UR - http://www.scopus.com/inward/record.url?scp=85062969795&partnerID=8YFLogxK

U2 - 10.1002/celc.201900028

DO - 10.1002/celc.201900028

M3 - Article

VL - 6

SP - 4284

EP - 4291

JO - ChemElectroChem

JF - ChemElectroChem

SN - 2196-0216

IS - 16

ER -