A Cascade Strategy Enables a Total Synthesis of (±)‐Morphine

Morphine has been a target for synthetic chemists since Robinson proposed its correct structure in 1925, resulting in a large number of total syntheses of morphine alkaloids. Here we report a total synthesis of (±)‐morphine that employs two key strategic cyclizations: 1) a diastereoselective light‐m...

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Detalles Bibliográficos
Autores principales: Chu, Shuyu, Münster, Niels, Balan, Tudor, Smith, Martin D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2016
Materias:
Communications
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5129523/
https://www.ncbi.nlm.nih.gov/pubmed/27735107
http://dx.doi.org/10.1002/anie.201608526
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author Chu, Shuyu
Münster, Niels
Balan, Tudor
Smith, Martin D.
author_facet Chu, Shuyu
Münster, Niels
Balan, Tudor
Smith, Martin D.
author_sort Chu, Shuyu
collection PubMed
description Morphine has been a target for synthetic chemists since Robinson proposed its correct structure in 1925, resulting in a large number of total syntheses of morphine alkaloids. Here we report a total synthesis of (±)‐morphine that employs two key strategic cyclizations: 1) a diastereoselective light‐mediated cyclization of an O‐arylated butyrolactone to form a tricyclic cis‐fused benzofuran and 2) a cascade ene–yne–ene ring closing metathesis to forge the tetracyclic morphine core. This approach enables a short and stereoselective synthesis of morphine in an overall yield of 6.6 %.
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spelling pubmed-51295232016-11-30 A Cascade Strategy Enables a Total Synthesis of (±)‐Morphine Chu, Shuyu Münster, Niels Balan, Tudor Smith, Martin D. Angew Chem Int Ed Engl Communications Morphine has been a target for synthetic chemists since Robinson proposed its correct structure in 1925, resulting in a large number of total syntheses of morphine alkaloids. Here we report a total synthesis of (±)‐morphine that employs two key strategic cyclizations: 1) a diastereoselective light‐mediated cyclization of an O‐arylated butyrolactone to form a tricyclic cis‐fused benzofuran and 2) a cascade ene–yne–ene ring closing metathesis to forge the tetracyclic morphine core. This approach enables a short and stereoselective synthesis of morphine in an overall yield of 6.6 %. John Wiley and Sons Inc. 2016-10-13 2016-11-07 /pmc/articles/PMC5129523/ /pubmed/27735107 http://dx.doi.org/10.1002/anie.201608526 Text en © 2016 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Communications
Chu, Shuyu
Münster, Niels
Balan, Tudor
Smith, Martin D.
A Cascade Strategy Enables a Total Synthesis of (±)‐Morphine
title A Cascade Strategy Enables a Total Synthesis of (±)‐Morphine
title_full A Cascade Strategy Enables a Total Synthesis of (±)‐Morphine
title_fullStr A Cascade Strategy Enables a Total Synthesis of (±)‐Morphine
title_full_unstemmed A Cascade Strategy Enables a Total Synthesis of (±)‐Morphine
title_short A Cascade Strategy Enables a Total Synthesis of (±)‐Morphine
title_sort cascade strategy enables a total synthesis of (±)‐morphine
topic Communications
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5129523/
https://www.ncbi.nlm.nih.gov/pubmed/27735107
http://dx.doi.org/10.1002/anie.201608526
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