[2 + 2 + 2] Cyclotrimerization with Propargyl Halides as Copartners: Formal Total Synthesis of the Antitumor Hsp90 Inhibitor AT13387

[Image: see text] Heat shock protein 90 (Hsp90) inhibitors play a remarkable role in cellular growth, and they were shown to exhibit antitumor activity. The Hsp90 inhibitor AT13387 (onalespib) is under clinical trials for the treatment of refractory gastrointestinal stromal tumors. Recently, it was...

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Autores principales: Kotha, Sambasivarao, Sreevani, Gaddamedi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2018
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6641397/
https://www.ncbi.nlm.nih.gov/pubmed/31458497
http://dx.doi.org/10.1021/acsomega.7b01976
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author Kotha, Sambasivarao
Sreevani, Gaddamedi
author_facet Kotha, Sambasivarao
Sreevani, Gaddamedi
author_sort Kotha, Sambasivarao
collection PubMed
description [Image: see text] Heat shock protein 90 (Hsp90) inhibitors play a remarkable role in cellular growth, and they were shown to exhibit antitumor activity. The Hsp90 inhibitor AT13387 (onalespib) is under clinical trials for the treatment of refractory gastrointestinal stromal tumors. Recently, it was demonstrated that this compound also exhibits inhibition against bladder cancer. Here, we report isoindoline- and isoindolinone-based (halomethyl)benzenes via a [2 + 2 + 2] cyclotrimerization in the presence of catalytic amounts of Mo(CO)(6). This strategy has been extended to synthesize the key precursor of the Hsp90 inhibitor, AT13387.
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spelling pubmed-66413972019-08-27 [2 + 2 + 2] Cyclotrimerization with Propargyl Halides as Copartners: Formal Total Synthesis of the Antitumor Hsp90 Inhibitor AT13387 Kotha, Sambasivarao Sreevani, Gaddamedi ACS Omega [Image: see text] Heat shock protein 90 (Hsp90) inhibitors play a remarkable role in cellular growth, and they were shown to exhibit antitumor activity. The Hsp90 inhibitor AT13387 (onalespib) is under clinical trials for the treatment of refractory gastrointestinal stromal tumors. Recently, it was demonstrated that this compound also exhibits inhibition against bladder cancer. Here, we report isoindoline- and isoindolinone-based (halomethyl)benzenes via a [2 + 2 + 2] cyclotrimerization in the presence of catalytic amounts of Mo(CO)(6). This strategy has been extended to synthesize the key precursor of the Hsp90 inhibitor, AT13387. American Chemical Society 2018-02-13 /pmc/articles/PMC6641397/ /pubmed/31458497 http://dx.doi.org/10.1021/acsomega.7b01976 Text en Copyright © 2018 American Chemical Society This is an open access article published under an ACS AuthorChoice License (http://pubs.acs.org/page/policy/authorchoice_termsofuse.html) , which permits copying and redistribution of the article or any adaptations for non-commercial purposes.
spellingShingle Kotha, Sambasivarao
Sreevani, Gaddamedi
[2 + 2 + 2] Cyclotrimerization with Propargyl Halides as Copartners: Formal Total Synthesis of the Antitumor Hsp90 Inhibitor AT13387
title [2 + 2 + 2] Cyclotrimerization with Propargyl Halides as Copartners: Formal Total Synthesis of the Antitumor Hsp90 Inhibitor AT13387
title_full [2 + 2 + 2] Cyclotrimerization with Propargyl Halides as Copartners: Formal Total Synthesis of the Antitumor Hsp90 Inhibitor AT13387
title_fullStr [2 + 2 + 2] Cyclotrimerization with Propargyl Halides as Copartners: Formal Total Synthesis of the Antitumor Hsp90 Inhibitor AT13387
title_full_unstemmed [2 + 2 + 2] Cyclotrimerization with Propargyl Halides as Copartners: Formal Total Synthesis of the Antitumor Hsp90 Inhibitor AT13387
title_short [2 + 2 + 2] Cyclotrimerization with Propargyl Halides as Copartners: Formal Total Synthesis of the Antitumor Hsp90 Inhibitor AT13387
title_sort [2 + 2 + 2] cyclotrimerization with propargyl halides as copartners: formal total synthesis of the antitumor hsp90 inhibitor at13387
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6641397/
https://www.ncbi.nlm.nih.gov/pubmed/31458497
http://dx.doi.org/10.1021/acsomega.7b01976
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