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Concise synthesis of (R)-reticuline and (+)-salutaridine by combining early-stage organic synthesis and late-stage biocatalysis
Efficient access to the morphinan scaffold remains a major challenge in both synthetic chemistry and biotechnology. Here, a biomimetic chemo-enzymatic strategy to synthesize the natural promorphinan intermediate (+)-salutaridine is demonstrated. By combining early-stage organic synthesis with enzyma...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Royal Society of Chemistry
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10510765/ https://www.ncbi.nlm.nih.gov/pubmed/37736642 http://dx.doi.org/10.1039/d3sc02304d |
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author | Cigan, Emmanuel Pletz, Jakob Berger, Sarah A. Hierzberger, Bettina Grilec-Zlamal, Michael Steiner, Alexander Oroz-Guinea, Isabel Kroutil, Wolfgang |
author_facet | Cigan, Emmanuel Pletz, Jakob Berger, Sarah A. Hierzberger, Bettina Grilec-Zlamal, Michael Steiner, Alexander Oroz-Guinea, Isabel Kroutil, Wolfgang |
author_sort | Cigan, Emmanuel |
collection | PubMed |
description | Efficient access to the morphinan scaffold remains a major challenge in both synthetic chemistry and biotechnology. Here, a biomimetic chemo-enzymatic strategy to synthesize the natural promorphinan intermediate (+)-salutaridine is demonstrated. By combining early-stage organic synthesis with enzymatic asymmetric key step transformations, the prochiral natural intermediate 1,2-dehydroreticuline was prepared and subsequently stereoselectively reduced by the enzyme 1,2-dehydroreticuline reductase obtaining (R)-reticuline in high ee and yield (>99% ee, up to quant. conversion, 92% isol. yield). In the final step, membrane-bound salutaridine synthase was used to perform the selective ortho-para phenol coupling to give (+)-salutaridine. The synthetic route shows the potential of combining early-stage advanced organic chemistry to minimize protecting group techniques with late-stage multi-step biocatalysis to provide an unprecedented access to the medicinally important compound class of promorphinans. |
format | Online Article Text |
id | pubmed-10510765 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | The Royal Society of Chemistry |
record_format | MEDLINE/PubMed |
spelling | pubmed-105107652023-09-21 Concise synthesis of (R)-reticuline and (+)-salutaridine by combining early-stage organic synthesis and late-stage biocatalysis Cigan, Emmanuel Pletz, Jakob Berger, Sarah A. Hierzberger, Bettina Grilec-Zlamal, Michael Steiner, Alexander Oroz-Guinea, Isabel Kroutil, Wolfgang Chem Sci Chemistry Efficient access to the morphinan scaffold remains a major challenge in both synthetic chemistry and biotechnology. Here, a biomimetic chemo-enzymatic strategy to synthesize the natural promorphinan intermediate (+)-salutaridine is demonstrated. By combining early-stage organic synthesis with enzymatic asymmetric key step transformations, the prochiral natural intermediate 1,2-dehydroreticuline was prepared and subsequently stereoselectively reduced by the enzyme 1,2-dehydroreticuline reductase obtaining (R)-reticuline in high ee and yield (>99% ee, up to quant. conversion, 92% isol. yield). In the final step, membrane-bound salutaridine synthase was used to perform the selective ortho-para phenol coupling to give (+)-salutaridine. The synthetic route shows the potential of combining early-stage advanced organic chemistry to minimize protecting group techniques with late-stage multi-step biocatalysis to provide an unprecedented access to the medicinally important compound class of promorphinans. The Royal Society of Chemistry 2023-08-24 /pmc/articles/PMC10510765/ /pubmed/37736642 http://dx.doi.org/10.1039/d3sc02304d Text en This journal is © The Royal Society of Chemistry https://creativecommons.org/licenses/by/3.0/ |
spellingShingle | Chemistry Cigan, Emmanuel Pletz, Jakob Berger, Sarah A. Hierzberger, Bettina Grilec-Zlamal, Michael Steiner, Alexander Oroz-Guinea, Isabel Kroutil, Wolfgang Concise synthesis of (R)-reticuline and (+)-salutaridine by combining early-stage organic synthesis and late-stage biocatalysis |
title | Concise synthesis of (R)-reticuline and (+)-salutaridine by combining early-stage organic synthesis and late-stage biocatalysis |
title_full | Concise synthesis of (R)-reticuline and (+)-salutaridine by combining early-stage organic synthesis and late-stage biocatalysis |
title_fullStr | Concise synthesis of (R)-reticuline and (+)-salutaridine by combining early-stage organic synthesis and late-stage biocatalysis |
title_full_unstemmed | Concise synthesis of (R)-reticuline and (+)-salutaridine by combining early-stage organic synthesis and late-stage biocatalysis |
title_short | Concise synthesis of (R)-reticuline and (+)-salutaridine by combining early-stage organic synthesis and late-stage biocatalysis |
title_sort | concise synthesis of (r)-reticuline and (+)-salutaridine by combining early-stage organic synthesis and late-stage biocatalysis |
topic | Chemistry |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10510765/ https://www.ncbi.nlm.nih.gov/pubmed/37736642 http://dx.doi.org/10.1039/d3sc02304d |
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