Combined Enzyme- and Transition Metal-Catalyzed Strategy for the Enantioselective Syntheses of Nitrogen Heterocycles: (−)-Coniine, DAB-1, and Nectrisine

[Image: see text] The enantioselective syntheses of (−)-coniine, DAB-1, and nectrisine have been developed, utilizing a complementary strategy of enzyme- and transition metal-catalyzed reactions. The initial stereocenter was set with >99% enantioselectivity via an enzyme-catalyzed hydrocyanation...

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Autores principales: Deardorff, Donald R., Niman, Scott W., Paulsen, Mark I., Sookezian, Anasheh, Whalen, Meghan E., Finlayson, Christopher J., Frivold, Collrane, Brown, Hilary C., Cannon, Jeffrey S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2020
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7003507/
https://www.ncbi.nlm.nih.gov/pubmed/32039338
http://dx.doi.org/10.1021/acsomega.9b03990
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author Deardorff, Donald R.
Niman, Scott W.
Paulsen, Mark I.
Sookezian, Anasheh
Whalen, Meghan E.
Finlayson, Christopher J.
Frivold, Collrane
Brown, Hilary C.
Cannon, Jeffrey S.
author_facet Deardorff, Donald R.
Niman, Scott W.
Paulsen, Mark I.
Sookezian, Anasheh
Whalen, Meghan E.
Finlayson, Christopher J.
Frivold, Collrane
Brown, Hilary C.
Cannon, Jeffrey S.
author_sort Deardorff, Donald R.
collection PubMed
description [Image: see text] The enantioselective syntheses of (−)-coniine, DAB-1, and nectrisine have been developed, utilizing a complementary strategy of enzyme- and transition metal-catalyzed reactions. The initial stereocenter was set with >99% enantioselectivity via an enzyme-catalyzed hydrocyanation reaction. Substrate incompatibilities with the natural enzyme were overcome by tactical utilization of ruthenium-catalyzed olefin metathesis to functionalize an enzyme-derived (R)-allylic fragment. The piperidine and pyrrolidine alkaloid natural products were obtained by a route that leveraged regio- and stereoselective palladium-catalyzed 1,3-substitutive reactions.
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spelling pubmed-70035072020-02-07 Combined Enzyme- and Transition Metal-Catalyzed Strategy for the Enantioselective Syntheses of Nitrogen Heterocycles: (−)-Coniine, DAB-1, and Nectrisine Deardorff, Donald R. Niman, Scott W. Paulsen, Mark I. Sookezian, Anasheh Whalen, Meghan E. Finlayson, Christopher J. Frivold, Collrane Brown, Hilary C. Cannon, Jeffrey S. ACS Omega [Image: see text] The enantioselective syntheses of (−)-coniine, DAB-1, and nectrisine have been developed, utilizing a complementary strategy of enzyme- and transition metal-catalyzed reactions. The initial stereocenter was set with >99% enantioselectivity via an enzyme-catalyzed hydrocyanation reaction. Substrate incompatibilities with the natural enzyme were overcome by tactical utilization of ruthenium-catalyzed olefin metathesis to functionalize an enzyme-derived (R)-allylic fragment. The piperidine and pyrrolidine alkaloid natural products were obtained by a route that leveraged regio- and stereoselective palladium-catalyzed 1,3-substitutive reactions. American Chemical Society 2020-01-23 /pmc/articles/PMC7003507/ /pubmed/32039338 http://dx.doi.org/10.1021/acsomega.9b03990 Text en Copyright © 2020 American Chemical Society This is an open access article published under a Creative Commons Non-Commercial No Derivative Works (CC-BY-NC-ND) Attribution License (http://pubs.acs.org/page/policy/authorchoice_ccbyncnd_termsofuse.html) , which permits copying and redistribution of the article, and creation of adaptations, all for non-commercial purposes.
spellingShingle Deardorff, Donald R.
Niman, Scott W.
Paulsen, Mark I.
Sookezian, Anasheh
Whalen, Meghan E.
Finlayson, Christopher J.
Frivold, Collrane
Brown, Hilary C.
Cannon, Jeffrey S.
Combined Enzyme- and Transition Metal-Catalyzed Strategy for the Enantioselective Syntheses of Nitrogen Heterocycles: (−)-Coniine, DAB-1, and Nectrisine
title Combined Enzyme- and Transition Metal-Catalyzed Strategy for the Enantioselective Syntheses of Nitrogen Heterocycles: (−)-Coniine, DAB-1, and Nectrisine
title_full Combined Enzyme- and Transition Metal-Catalyzed Strategy for the Enantioselective Syntheses of Nitrogen Heterocycles: (−)-Coniine, DAB-1, and Nectrisine
title_fullStr Combined Enzyme- and Transition Metal-Catalyzed Strategy for the Enantioselective Syntheses of Nitrogen Heterocycles: (−)-Coniine, DAB-1, and Nectrisine
title_full_unstemmed Combined Enzyme- and Transition Metal-Catalyzed Strategy for the Enantioselective Syntheses of Nitrogen Heterocycles: (−)-Coniine, DAB-1, and Nectrisine
title_short Combined Enzyme- and Transition Metal-Catalyzed Strategy for the Enantioselective Syntheses of Nitrogen Heterocycles: (−)-Coniine, DAB-1, and Nectrisine
title_sort combined enzyme- and transition metal-catalyzed strategy for the enantioselective syntheses of nitrogen heterocycles: (−)-coniine, dab-1, and nectrisine
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7003507/
https://www.ncbi.nlm.nih.gov/pubmed/32039338
http://dx.doi.org/10.1021/acsomega.9b03990
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