Cargando…
A Domino 10-Step Total Synthesis of FR252921 and Its Analogues, Complex Macrocyclic Immunosuppressants
[Image: see text] FR252921, FR252922, and FR256523 are a family of potent macrocyclic polyene immunosuppressive agents with a novel mode of action. However, the lack of an efficient and flexible synthesis has hindered further biological studies, mostly due to the fact that the natural products appea...
Autores principales: | , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Chemical
Society
2019
|
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6837725/ https://www.ncbi.nlm.nih.gov/pubmed/31436963 http://dx.doi.org/10.1021/jacs.9b07185 |
_version_ | 1783467099810693120 |
---|---|
author | Chen, Yong Coussanes, Guilhem Souris, Caroline Aillard, Paul Kaldre, Dainis Runggatscher, Kathrin Kubicek, Stefan Di Mauro, Giovanni Maryasin, Boris Maulide, Nuno |
author_facet | Chen, Yong Coussanes, Guilhem Souris, Caroline Aillard, Paul Kaldre, Dainis Runggatscher, Kathrin Kubicek, Stefan Di Mauro, Giovanni Maryasin, Boris Maulide, Nuno |
author_sort | Chen, Yong |
collection | PubMed |
description | [Image: see text] FR252921, FR252922, and FR256523 are a family of potent macrocyclic polyene immunosuppressive agents with a novel mode of action. However, the lack of an efficient and flexible synthesis has hindered further biological studies, mostly due to the fact that the natural products appear to be kinetic isomers regarding the triene moiety. Herein, we report the development and application of an unprecedented, unique domino Suzuki–Miyaura/4π-electrocyclic ring-opening macrocyclization, resulting in a concise, unified, and stereoselective synthetic route to these complex targets in only 10 steps. This in turn enables ready access to a range of unnatural analogues, among which several compounds showed inhibition of T-lymphocyte proliferation at levels equal or superior to those of the natural products themselves. |
format | Online Article Text |
id | pubmed-6837725 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | American Chemical
Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-68377252019-11-08 A Domino 10-Step Total Synthesis of FR252921 and Its Analogues, Complex Macrocyclic Immunosuppressants Chen, Yong Coussanes, Guilhem Souris, Caroline Aillard, Paul Kaldre, Dainis Runggatscher, Kathrin Kubicek, Stefan Di Mauro, Giovanni Maryasin, Boris Maulide, Nuno J Am Chem Soc [Image: see text] FR252921, FR252922, and FR256523 are a family of potent macrocyclic polyene immunosuppressive agents with a novel mode of action. However, the lack of an efficient and flexible synthesis has hindered further biological studies, mostly due to the fact that the natural products appear to be kinetic isomers regarding the triene moiety. Herein, we report the development and application of an unprecedented, unique domino Suzuki–Miyaura/4π-electrocyclic ring-opening macrocyclization, resulting in a concise, unified, and stereoselective synthetic route to these complex targets in only 10 steps. This in turn enables ready access to a range of unnatural analogues, among which several compounds showed inhibition of T-lymphocyte proliferation at levels equal or superior to those of the natural products themselves. American Chemical Society 2019-08-22 2019-09-04 /pmc/articles/PMC6837725/ /pubmed/31436963 http://dx.doi.org/10.1021/jacs.9b07185 Text en Copyright © 2019 American Chemical Society This is an open access article published under a Creative Commons Attribution (CC-BY) License (http://pubs.acs.org/page/policy/authorchoice_ccby_termsofuse.html) , which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited. |
spellingShingle | Chen, Yong Coussanes, Guilhem Souris, Caroline Aillard, Paul Kaldre, Dainis Runggatscher, Kathrin Kubicek, Stefan Di Mauro, Giovanni Maryasin, Boris Maulide, Nuno A Domino 10-Step Total Synthesis of FR252921 and Its Analogues, Complex Macrocyclic Immunosuppressants |
title | A Domino
10-Step Total Synthesis of FR252921 and Its
Analogues, Complex Macrocyclic Immunosuppressants |
title_full | A Domino
10-Step Total Synthesis of FR252921 and Its
Analogues, Complex Macrocyclic Immunosuppressants |
title_fullStr | A Domino
10-Step Total Synthesis of FR252921 and Its
Analogues, Complex Macrocyclic Immunosuppressants |
title_full_unstemmed | A Domino
10-Step Total Synthesis of FR252921 and Its
Analogues, Complex Macrocyclic Immunosuppressants |
title_short | A Domino
10-Step Total Synthesis of FR252921 and Its
Analogues, Complex Macrocyclic Immunosuppressants |
title_sort | domino
10-step total synthesis of fr252921 and its
analogues, complex macrocyclic immunosuppressants |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6837725/ https://www.ncbi.nlm.nih.gov/pubmed/31436963 http://dx.doi.org/10.1021/jacs.9b07185 |
work_keys_str_mv | AT chenyong adomino10steptotalsynthesisoffr252921anditsanaloguescomplexmacrocyclicimmunosuppressants AT coussanesguilhem adomino10steptotalsynthesisoffr252921anditsanaloguescomplexmacrocyclicimmunosuppressants AT souriscaroline adomino10steptotalsynthesisoffr252921anditsanaloguescomplexmacrocyclicimmunosuppressants AT aillardpaul adomino10steptotalsynthesisoffr252921anditsanaloguescomplexmacrocyclicimmunosuppressants AT kaldredainis adomino10steptotalsynthesisoffr252921anditsanaloguescomplexmacrocyclicimmunosuppressants AT runggatscherkathrin adomino10steptotalsynthesisoffr252921anditsanaloguescomplexmacrocyclicimmunosuppressants AT kubicekstefan adomino10steptotalsynthesisoffr252921anditsanaloguescomplexmacrocyclicimmunosuppressants AT dimaurogiovanni adomino10steptotalsynthesisoffr252921anditsanaloguescomplexmacrocyclicimmunosuppressants AT maryasinboris adomino10steptotalsynthesisoffr252921anditsanaloguescomplexmacrocyclicimmunosuppressants AT maulidenuno adomino10steptotalsynthesisoffr252921anditsanaloguescomplexmacrocyclicimmunosuppressants AT chenyong domino10steptotalsynthesisoffr252921anditsanaloguescomplexmacrocyclicimmunosuppressants AT coussanesguilhem domino10steptotalsynthesisoffr252921anditsanaloguescomplexmacrocyclicimmunosuppressants AT souriscaroline domino10steptotalsynthesisoffr252921anditsanaloguescomplexmacrocyclicimmunosuppressants AT aillardpaul domino10steptotalsynthesisoffr252921anditsanaloguescomplexmacrocyclicimmunosuppressants AT kaldredainis domino10steptotalsynthesisoffr252921anditsanaloguescomplexmacrocyclicimmunosuppressants AT runggatscherkathrin domino10steptotalsynthesisoffr252921anditsanaloguescomplexmacrocyclicimmunosuppressants AT kubicekstefan domino10steptotalsynthesisoffr252921anditsanaloguescomplexmacrocyclicimmunosuppressants AT dimaurogiovanni domino10steptotalsynthesisoffr252921anditsanaloguescomplexmacrocyclicimmunosuppressants AT maryasinboris domino10steptotalsynthesisoffr252921anditsanaloguescomplexmacrocyclicimmunosuppressants AT maulidenuno domino10steptotalsynthesisoffr252921anditsanaloguescomplexmacrocyclicimmunosuppressants |