One-Pot Biocatalytic Cascade Reduction of Cyclic Enimines for the Preparation of Diastereomerically Enriched N-Heterocycles

Thomas W. Thorpe; Scott P. France; Shahed Hussain; James R. Marshall; Wojciech Zawodny; Juan Mangas-sanchez; Sarah L. Montgomery; Roger M. Howard; David S. B. Daniels; Rajesh Kumar; Fabio Parmeggiani; Nicholas J. Turner

doi:10.1021/jacs.9b10053

One-Pot Biocatalytic Cascade Reduction of Cyclic Enimines for the Preparation of Diastereomerically Enriched N-Heterocycles

Thomas W. Thorpe, Scott P. France, Shahed Hussain, James R. Marshall, Wojciech Zawodny, Juan Mangas-sanchez, Sarah L. Montgomery, Roger M. Howard, David S. B. Daniels, Rajesh Kumar, Fabio Parmeggiani, Nicholas J. Turner

Research output: Contribution to journal › Article › peer-review

146 Downloads (Pure)

Abstract

Ene-reductases (EREDs) catalyze the reduction of electron-deﬁcient CC bonds. Herein, we report the ﬁrst example of ERED-catalyzed net reduction of CC bonds of enimines (α,β-unsaturated imines). Preliminary studies suggest their hydrolyzed ring-open ωamino enones are the likely substrates for this step. When combined with imine reductase (IRED)-mediated CN reduction, the result is an eﬃcient telescoped sequence for the preparation of diastereomerically enriched 2-substituted saturated amine heterocycles.

Original language	English
Pages (from-to)	19208-19213
Journal	Journal of the American Chemical Society
Volume	141
Issue number	49
Early online date	19 Nov 2019
DOIs	https://doi.org/10.1021/jacs.9b10053
Publication status	Published - 11 Dec 2019

Access to Document

10.1021/jacs.9b10053

jacs.9b10053 JUST ACCEPTEDAccepted author manuscript, 524 KB

https://pubs.acs.org/doi/10.1021/jacs.9b10053

Cite this

Thorpe, T. W., France, S. P., Hussain, S., Marshall, J. R., Zawodny, W., Mangas-sanchez, J., Montgomery, S. L., Howard, R. M., Daniels, D. S. B., Kumar, R., Parmeggiani, F., & Turner, N. J. (2019). One-Pot Biocatalytic Cascade Reduction of Cyclic Enimines for the Preparation of Diastereomerically Enriched N-Heterocycles. Journal of the American Chemical Society, 141(49), 19208-19213. https://doi.org/10.1021/jacs.9b10053

@article{6b132240800e4d54af4624733fa81f73,

title = "One-Pot Biocatalytic Cascade Reduction of Cyclic Enimines for the Preparation of Diastereomerically Enriched N-Heterocycles",

abstract = "Ene-reductases (EREDs) catalyze the reduction of electron-deﬁcient CC bonds. Herein, we report the ﬁrst example of ERED-catalyzed net reduction of CC bonds of enimines (α,β-unsaturated imines). Preliminary studies suggest their hydrolyzed ring-open ωamino enones are the likely substrates for this step. When combined with imine reductase (IRED)-mediated CN reduction, the result is an eﬃcient telescoped sequence for the preparation of diastereomerically enriched 2-substituted saturated amine heterocycles. ",

author = "Thorpe, {Thomas W.} and France, {Scott P.} and Shahed Hussain and Marshall, {James R.} and Wojciech Zawodny and Juan Mangas-sanchez and Montgomery, {Sarah L.} and Howard, {Roger M.} and Daniels, {David S. B.} and Rajesh Kumar and Fabio Parmeggiani and Turner, {Nicholas J.}",

year = "2019",

month = dec,

day = "11",

doi = "10.1021/jacs.9b10053",

language = "English",

volume = "141",

pages = "19208--19213",

journal = "Journal of the American Chemical Society",

issn = "0002-7863",

publisher = "American Chemical Society",

number = "49",

}

Thorpe, TW, France, SP, Hussain, S, Marshall, JR, Zawodny, W, Mangas-sanchez, J, Montgomery, SL, Howard, RM, Daniels, DSB, Kumar, R, Parmeggiani, F & Turner, NJ 2019, 'One-Pot Biocatalytic Cascade Reduction of Cyclic Enimines for the Preparation of Diastereomerically Enriched N-Heterocycles', Journal of the American Chemical Society, vol. 141, no. 49, pp. 19208-19213. https://doi.org/10.1021/jacs.9b10053

TY - JOUR

T1 - One-Pot Biocatalytic Cascade Reduction of Cyclic Enimines for the Preparation of Diastereomerically Enriched N-Heterocycles

AU - Thorpe, Thomas W.

AU - France, Scott P.

AU - Hussain, Shahed

AU - Marshall, James R.

AU - Zawodny, Wojciech

AU - Mangas-sanchez, Juan

AU - Montgomery, Sarah L.

AU - Howard, Roger M.

AU - Daniels, David S. B.

AU - Kumar, Rajesh

AU - Parmeggiani, Fabio

AU - Turner, Nicholas J.

PY - 2019/12/11

Y1 - 2019/12/11

N2 - Ene-reductases (EREDs) catalyze the reduction of electron-deﬁcient CC bonds. Herein, we report the ﬁrst example of ERED-catalyzed net reduction of CC bonds of enimines (α,β-unsaturated imines). Preliminary studies suggest their hydrolyzed ring-open ωamino enones are the likely substrates for this step. When combined with imine reductase (IRED)-mediated CN reduction, the result is an eﬃcient telescoped sequence for the preparation of diastereomerically enriched 2-substituted saturated amine heterocycles.

AB - Ene-reductases (EREDs) catalyze the reduction of electron-deﬁcient CC bonds. Herein, we report the ﬁrst example of ERED-catalyzed net reduction of CC bonds of enimines (α,β-unsaturated imines). Preliminary studies suggest their hydrolyzed ring-open ωamino enones are the likely substrates for this step. When combined with imine reductase (IRED)-mediated CN reduction, the result is an eﬃcient telescoped sequence for the preparation of diastereomerically enriched 2-substituted saturated amine heterocycles.

U2 - 10.1021/jacs.9b10053

DO - 10.1021/jacs.9b10053

M3 - Article

SN - 0002-7863

VL - 141

SP - 19208

EP - 19213

JO - Journal of the American Chemical Society

JF - Journal of the American Chemical Society

IS - 49

ER -

One-Pot Biocatalytic Cascade Reduction of Cyclic Enimines for the Preparation of Diastereomerically Enriched N-Heterocycles

Abstract

Access to Document

Fingerprint

Cite this