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Regiodivergent synthesis of sulfone-tethered lactam–lactones bearing four contiguous stereocenters
Sulfone-tethered lactones/amides/amines display a diverse spectrum of biological activities, including anti-psychotic and anti-hypertensive. Sulfones are also widely present in functional materials and fragrances. We therefore reasoned that a regiodivergent and stereocontrolled strategy that merges...
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/PMC10340014/ https://www.ncbi.nlm.nih.gov/pubmed/37456540 http://dx.doi.org/10.1039/d3ra03800a |
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author | Beng, Timothy K. Eichwald, Jane Fessenden, Jolyn Quigley, Kaiden Sharaf, Sapna Jeon, Nanju Do, Minh |
author_facet | Beng, Timothy K. Eichwald, Jane Fessenden, Jolyn Quigley, Kaiden Sharaf, Sapna Jeon, Nanju Do, Minh |
author_sort | Beng, Timothy K. |
collection | PubMed |
description | Sulfone-tethered lactones/amides/amines display a diverse spectrum of biological activities, including anti-psychotic and anti-hypertensive. Sulfones are also widely present in functional materials and fragrances. We therefore reasoned that a regiodivergent and stereocontrolled strategy that merges the sulfone, lactone, and lactam motifs would likely lead to the discovery of new pharmacophores and functional materials. Here, we report mild conditions for the sulfonyllactonization of γ-lactam-tethered 5-aryl-4(E)-pentenoic acids. The annulation is highly modular, chemoselective, and diastereoselective. With respect to regioselectivity, trisubstituted alkenoic acids display a preference for 5-exo-trig cyclization whereas disubstituted alkenoic acids undergo exclusive 6-endo-trig cyclization. The lactam-fused sulfonyllactones bear angular quaternary as well as four contiguous stereocenters. The products are post-modifiable, especially through a newly developed Co-catalyzed reductive cross-coupling protocol. |
format | Online Article Text |
id | pubmed-10340014 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | The Royal Society of Chemistry |
record_format | MEDLINE/PubMed |
spelling | pubmed-103400142023-07-14 Regiodivergent synthesis of sulfone-tethered lactam–lactones bearing four contiguous stereocenters Beng, Timothy K. Eichwald, Jane Fessenden, Jolyn Quigley, Kaiden Sharaf, Sapna Jeon, Nanju Do, Minh RSC Adv Chemistry Sulfone-tethered lactones/amides/amines display a diverse spectrum of biological activities, including anti-psychotic and anti-hypertensive. Sulfones are also widely present in functional materials and fragrances. We therefore reasoned that a regiodivergent and stereocontrolled strategy that merges the sulfone, lactone, and lactam motifs would likely lead to the discovery of new pharmacophores and functional materials. Here, we report mild conditions for the sulfonyllactonization of γ-lactam-tethered 5-aryl-4(E)-pentenoic acids. The annulation is highly modular, chemoselective, and diastereoselective. With respect to regioselectivity, trisubstituted alkenoic acids display a preference for 5-exo-trig cyclization whereas disubstituted alkenoic acids undergo exclusive 6-endo-trig cyclization. The lactam-fused sulfonyllactones bear angular quaternary as well as four contiguous stereocenters. The products are post-modifiable, especially through a newly developed Co-catalyzed reductive cross-coupling protocol. The Royal Society of Chemistry 2023-07-13 /pmc/articles/PMC10340014/ /pubmed/37456540 http://dx.doi.org/10.1039/d3ra03800a Text en This journal is © The Royal Society of Chemistry https://creativecommons.org/licenses/by-nc/3.0/ |
spellingShingle | Chemistry Beng, Timothy K. Eichwald, Jane Fessenden, Jolyn Quigley, Kaiden Sharaf, Sapna Jeon, Nanju Do, Minh Regiodivergent synthesis of sulfone-tethered lactam–lactones bearing four contiguous stereocenters |
title | Regiodivergent synthesis of sulfone-tethered lactam–lactones bearing four contiguous stereocenters |
title_full | Regiodivergent synthesis of sulfone-tethered lactam–lactones bearing four contiguous stereocenters |
title_fullStr | Regiodivergent synthesis of sulfone-tethered lactam–lactones bearing four contiguous stereocenters |
title_full_unstemmed | Regiodivergent synthesis of sulfone-tethered lactam–lactones bearing four contiguous stereocenters |
title_short | Regiodivergent synthesis of sulfone-tethered lactam–lactones bearing four contiguous stereocenters |
title_sort | regiodivergent synthesis of sulfone-tethered lactam–lactones bearing four contiguous stereocenters |
topic | Chemistry |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10340014/ https://www.ncbi.nlm.nih.gov/pubmed/37456540 http://dx.doi.org/10.1039/d3ra03800a |
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