Synthesis of a des-B-Ring Bryostatin Analogue Leads to an Unexpected Ring Expansion of the Bryolactone Core

[Image: see text] A convergent synthesis of a des-B-ring bryostatin analogue is described. This analogue was found to undergo an unexpected ring expansion of the bryolactone core to generate the corresponding 21-membered macrocycle. The parent analogue and the ring-expanded product both displayed na...

Descripción completa

Detalles Bibliográficos
Autores principales: Kraft, Matthew B., Poudel, Yam B., Kedei, Noemi, Lewin, Nancy E., Peach, Megan L., Blumberg, Peter M., Keck, Gary E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2014
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4183620/
https://www.ncbi.nlm.nih.gov/pubmed/25207434
http://dx.doi.org/10.1021/ja5078188
_version_ 1782337727517163520
author Kraft, Matthew B.
Poudel, Yam B.
Kedei, Noemi
Lewin, Nancy E.
Peach, Megan L.
Blumberg, Peter M.
Keck, Gary E.
author_facet Kraft, Matthew B.
Poudel, Yam B.
Kedei, Noemi
Lewin, Nancy E.
Peach, Megan L.
Blumberg, Peter M.
Keck, Gary E.
author_sort Kraft, Matthew B.
collection PubMed
description [Image: see text] A convergent synthesis of a des-B-ring bryostatin analogue is described. This analogue was found to undergo an unexpected ring expansion of the bryolactone core to generate the corresponding 21-membered macrocycle. The parent analogue and the ring-expanded product both displayed nanomolar binding affinity for PKC. Despite containing A-ring substitution identical to that of bryostatin 1 and displaying bryostatin-like biological function, the des-B-ring analogues displayed a phorbol-like biological function in cells. These studies shed new light on the role of the bryostatin B-ring in conferring bryo-like biological function to bryostatin analogues.
format Online
Article
Text
id pubmed-4183620
institution National Center for Biotechnology Information
language English
publishDate 2014
publisher American Chemical Society
record_format MEDLINE/PubMed
spelling pubmed-41836202015-09-10 Synthesis of a des-B-Ring Bryostatin Analogue Leads to an Unexpected Ring Expansion of the Bryolactone Core Kraft, Matthew B. Poudel, Yam B. Kedei, Noemi Lewin, Nancy E. Peach, Megan L. Blumberg, Peter M. Keck, Gary E. J Am Chem Soc [Image: see text] A convergent synthesis of a des-B-ring bryostatin analogue is described. This analogue was found to undergo an unexpected ring expansion of the bryolactone core to generate the corresponding 21-membered macrocycle. The parent analogue and the ring-expanded product both displayed nanomolar binding affinity for PKC. Despite containing A-ring substitution identical to that of bryostatin 1 and displaying bryostatin-like biological function, the des-B-ring analogues displayed a phorbol-like biological function in cells. These studies shed new light on the role of the bryostatin B-ring in conferring bryo-like biological function to bryostatin analogues. American Chemical Society 2014-09-10 2014-09-24 /pmc/articles/PMC4183620/ /pubmed/25207434 http://dx.doi.org/10.1021/ja5078188 Text en Copyright © 2014 American Chemical Society Terms of Use (http://pubs.acs.org/page/policy/authorchoice_termsofuse.html)
spellingShingle Kraft, Matthew B.
Poudel, Yam B.
Kedei, Noemi
Lewin, Nancy E.
Peach, Megan L.
Blumberg, Peter M.
Keck, Gary E.
Synthesis of a des-B-Ring Bryostatin Analogue Leads to an Unexpected Ring Expansion of the Bryolactone Core
title Synthesis of a des-B-Ring Bryostatin Analogue Leads to an Unexpected Ring Expansion of the Bryolactone Core
title_full Synthesis of a des-B-Ring Bryostatin Analogue Leads to an Unexpected Ring Expansion of the Bryolactone Core
title_fullStr Synthesis of a des-B-Ring Bryostatin Analogue Leads to an Unexpected Ring Expansion of the Bryolactone Core
title_full_unstemmed Synthesis of a des-B-Ring Bryostatin Analogue Leads to an Unexpected Ring Expansion of the Bryolactone Core
title_short Synthesis of a des-B-Ring Bryostatin Analogue Leads to an Unexpected Ring Expansion of the Bryolactone Core
title_sort synthesis of a des-b-ring bryostatin analogue leads to an unexpected ring expansion of the bryolactone core
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4183620/
https://www.ncbi.nlm.nih.gov/pubmed/25207434
http://dx.doi.org/10.1021/ja5078188
work_keys_str_mv AT kraftmatthewb synthesisofadesbringbryostatinanalogueleadstoanunexpectedringexpansionofthebryolactonecore
AT poudelyamb synthesisofadesbringbryostatinanalogueleadstoanunexpectedringexpansionofthebryolactonecore
AT kedeinoemi synthesisofadesbringbryostatinanalogueleadstoanunexpectedringexpansionofthebryolactonecore
AT lewinnancye synthesisofadesbringbryostatinanalogueleadstoanunexpectedringexpansionofthebryolactonecore
AT peachmeganl synthesisofadesbringbryostatinanalogueleadstoanunexpectedringexpansionofthebryolactonecore
AT blumbergpeterm synthesisofadesbringbryostatinanalogueleadstoanunexpectedringexpansionofthebryolactonecore
AT keckgarye synthesisofadesbringbryostatinanalogueleadstoanunexpectedringexpansionofthebryolactonecore

Ejemplares similares