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Philipp Petermeier

Asymmetric synthesis of dihydropinidine enabled by concurrent multienzyme catalysis and a biocatalytic alternative to krapcho dealkoxycarbonylation

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Standard

Asymmetric synthesis of dihydropinidine enabled by concurrent multienzyme catalysis and a biocatalytic alternative to krapcho dealkoxycarbonylation. / Alvarenga, Natalia; Payer, Stefan E.; Petermeier, Philipp et al.

In: A C S Catalysis, Vol. 10, No. 2, 01.2020, p. 1607-1620.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

Harvard

Alvarenga, N, Payer, SE, Petermeier, P, Kohlfuerst, C, Meleiro Porto, AL, Schrittwieser, JH & Kroutil, W 2020, 'Asymmetric synthesis of dihydropinidine enabled by concurrent multienzyme catalysis and a biocatalytic alternative to krapcho dealkoxycarbonylation', A C S Catalysis, vol. 10, no. 2, pp. 1607-1620. https://doi.org/10.1021/acscatal.9b04611

APA

Alvarenga, N., Payer, S. E., Petermeier, P., Kohlfuerst, C., Meleiro Porto, A. L., Schrittwieser, J. H., & Kroutil, W. (2020). Asymmetric synthesis of dihydropinidine enabled by concurrent multienzyme catalysis and a biocatalytic alternative to krapcho dealkoxycarbonylation. A C S Catalysis, 10(2), 1607-1620. https://doi.org/10.1021/acscatal.9b04611

CBE

Alvarenga N, Payer SE, Petermeier P, Kohlfuerst C, Meleiro Porto AL, Schrittwieser JH, Kroutil W. 2020. Asymmetric synthesis of dihydropinidine enabled by concurrent multienzyme catalysis and a biocatalytic alternative to krapcho dealkoxycarbonylation. A C S Catalysis. 10(2):1607-1620. https://doi.org/10.1021/acscatal.9b04611

MLA

Alvarenga, Natalia et al. "Asymmetric synthesis of dihydropinidine enabled by concurrent multienzyme catalysis and a biocatalytic alternative to krapcho dealkoxycarbonylation". A C S Catalysis. 2020, 10(2). 1607-1620. https://doi.org/10.1021/acscatal.9b04611

Vancouver

Alvarenga N, Payer SE, Petermeier P, Kohlfuerst C, Meleiro Porto AL, Schrittwieser JH et al. Asymmetric synthesis of dihydropinidine enabled by concurrent multienzyme catalysis and a biocatalytic alternative to krapcho dealkoxycarbonylation. A C S Catalysis. 2020 Jan;10(2):1607-1620. doi: 10.1021/acscatal.9b04611

Author

Alvarenga, Natalia ; Payer, Stefan E. ; Petermeier, Philipp et al. / Asymmetric synthesis of dihydropinidine enabled by concurrent multienzyme catalysis and a biocatalytic alternative to krapcho dealkoxycarbonylation. In: A C S Catalysis. 2020 ; Vol. 10, No. 2. pp. 1607-1620.

Bibtex

@article{b75e395ef1ef4b919c905fc05d695097,
title = "Asymmetric synthesis of dihydropinidine enabled by concurrent multienzyme catalysis and a biocatalytic alternative to krapcho dealkoxycarbonylation",
abstract = "Dihydropinidine is a piperidine alkaloid found in spruce needles that has shown promising antifeedant activity against the large pine weevil, a widespread and economically relevant pest of coniferous tree plantations. Chemo-enzymatic approaches have previously been shown to enable a step-economic access to both enantiomers of this alkaloid, but the scalability of these syntheses is limited. Herein, we report a chemo-enzymatic route to dihydropinidine that is dominated by biocatalytic steps and affords the target alkaloid in excellent stereoisomeric purity (>99% ee and de) and high yield (57% overall) on multigram scale. Our synthesis makes use of a solvent-free, Lewis acid-catalyzed Michael addition and a biocatalytic alternative to Krapcho dealkoxycarbonylation, achieved by pig liver esterase (PLE)-catalyzed ester hydrolysis and acidification, and specifically developed for this purpose, to access a key intermediate, nonane-2,6-dione. This diketone is then converted into dihydropinidine by a concurrent one-pot (cascade) biotransformation catalyzed by a transaminase, an imine reductase, and an alcohol dehydrogenase. High yields and excellent regio- and stereoselectivities of the individual transformations render chromatographic purification of intermediates unnecessary and make it possible to carry out the entire sequence with a final hydrochloride precipitation of the target alkaloid as the sole purification step",
author = "Natalia Alvarenga and Payer, {Stefan E.} and Philipp Petermeier and Christoph Kohlfuerst and {Meleiro Porto}, {Andre Luiz} and Schrittwieser, {Joerg H.} and Wolfgang Kroutil",
year = "2020",
month = jan,
doi = "10.1021/acscatal.9b04611",
language = "English",
volume = "10",
pages = "1607--1620",
journal = "A C S Catalysis",
issn = "2155-5435",
publisher = "American Chemical Society",
number = "2",

}

RIS

TY - JOUR

T1 - Asymmetric synthesis of dihydropinidine enabled by concurrent multienzyme catalysis and a biocatalytic alternative to krapcho dealkoxycarbonylation

AU - Alvarenga, Natalia

AU - Payer, Stefan E.

AU - Petermeier, Philipp

AU - Kohlfuerst, Christoph

AU - Meleiro Porto, Andre Luiz

AU - Schrittwieser, Joerg H.

AU - Kroutil, Wolfgang

PY - 2020/1

Y1 - 2020/1

N2 - Dihydropinidine is a piperidine alkaloid found in spruce needles that has shown promising antifeedant activity against the large pine weevil, a widespread and economically relevant pest of coniferous tree plantations. Chemo-enzymatic approaches have previously been shown to enable a step-economic access to both enantiomers of this alkaloid, but the scalability of these syntheses is limited. Herein, we report a chemo-enzymatic route to dihydropinidine that is dominated by biocatalytic steps and affords the target alkaloid in excellent stereoisomeric purity (>99% ee and de) and high yield (57% overall) on multigram scale. Our synthesis makes use of a solvent-free, Lewis acid-catalyzed Michael addition and a biocatalytic alternative to Krapcho dealkoxycarbonylation, achieved by pig liver esterase (PLE)-catalyzed ester hydrolysis and acidification, and specifically developed for this purpose, to access a key intermediate, nonane-2,6-dione. This diketone is then converted into dihydropinidine by a concurrent one-pot (cascade) biotransformation catalyzed by a transaminase, an imine reductase, and an alcohol dehydrogenase. High yields and excellent regio- and stereoselectivities of the individual transformations render chromatographic purification of intermediates unnecessary and make it possible to carry out the entire sequence with a final hydrochloride precipitation of the target alkaloid as the sole purification step

AB - Dihydropinidine is a piperidine alkaloid found in spruce needles that has shown promising antifeedant activity against the large pine weevil, a widespread and economically relevant pest of coniferous tree plantations. Chemo-enzymatic approaches have previously been shown to enable a step-economic access to both enantiomers of this alkaloid, but the scalability of these syntheses is limited. Herein, we report a chemo-enzymatic route to dihydropinidine that is dominated by biocatalytic steps and affords the target alkaloid in excellent stereoisomeric purity (>99% ee and de) and high yield (57% overall) on multigram scale. Our synthesis makes use of a solvent-free, Lewis acid-catalyzed Michael addition and a biocatalytic alternative to Krapcho dealkoxycarbonylation, achieved by pig liver esterase (PLE)-catalyzed ester hydrolysis and acidification, and specifically developed for this purpose, to access a key intermediate, nonane-2,6-dione. This diketone is then converted into dihydropinidine by a concurrent one-pot (cascade) biotransformation catalyzed by a transaminase, an imine reductase, and an alcohol dehydrogenase. High yields and excellent regio- and stereoselectivities of the individual transformations render chromatographic purification of intermediates unnecessary and make it possible to carry out the entire sequence with a final hydrochloride precipitation of the target alkaloid as the sole purification step

U2 - 10.1021/acscatal.9b04611

DO - 10.1021/acscatal.9b04611

M3 - Journal article

VL - 10

SP - 1607

EP - 1620

JO - A C S Catalysis

JF - A C S Catalysis

SN - 2155-5435

IS - 2

ER -