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A novel and practical synthesis of CAT3: a phenanthroindolizidine alkaloid with potential in treating glioblastoma

CAT3, one of the (+)-deoxytylophorinine-based phenanthroindolizidine alkaloids, is a promising therapeutic agent for the treatment of hedgehog (Hh)-driven glioblastoma and is currently being evaluated in preclinical studies. In this paper, a novel and practical synthetic route for CAT3 was firstly d...

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Autores principales: Wang, Ru-Bing, Lv, Hai-Ning, Zhu, Shan-Shan, Ren, Xiao-Dong, Xu, Song, Ma, Shuang-Gang, Liu, Yun-Bao, Qu, Jing, Yu, Shi-Shan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Royal Society of Chemistry 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9084470/
https://www.ncbi.nlm.nih.gov/pubmed/35547992
http://dx.doi.org/10.1039/c8ra04511a
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author Wang, Ru-Bing
Lv, Hai-Ning
Zhu, Shan-Shan
Ren, Xiao-Dong
Xu, Song
Ma, Shuang-Gang
Liu, Yun-Bao
Qu, Jing
Yu, Shi-Shan
author_facet Wang, Ru-Bing
Lv, Hai-Ning
Zhu, Shan-Shan
Ren, Xiao-Dong
Xu, Song
Ma, Shuang-Gang
Liu, Yun-Bao
Qu, Jing
Yu, Shi-Shan
author_sort Wang, Ru-Bing
collection PubMed
description CAT3, one of the (+)-deoxytylophorinine-based phenanthroindolizidine alkaloids, is a promising therapeutic agent for the treatment of hedgehog (Hh)-driven glioblastoma and is currently being evaluated in preclinical studies. In this paper, a novel and practical synthetic route for CAT3 was firstly demonstrated with 10% overall yield in 11 steps and has been successfully validated for pilot-plant scale preparation. Investigation of the substitution at the 3-position of phenanthrene revealed that the electron-donating functionality can well preserve the S configuration. In particular, the excellent enantiomeric excess of CAT3 (≥99% ee) was achieved by introducing the strongly electron-donating tert-butyldimethylsilyl (TBS) group.
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spelling pubmed-90844702022-05-10 A novel and practical synthesis of CAT3: a phenanthroindolizidine alkaloid with potential in treating glioblastoma Wang, Ru-Bing Lv, Hai-Ning Zhu, Shan-Shan Ren, Xiao-Dong Xu, Song Ma, Shuang-Gang Liu, Yun-Bao Qu, Jing Yu, Shi-Shan RSC Adv Chemistry CAT3, one of the (+)-deoxytylophorinine-based phenanthroindolizidine alkaloids, is a promising therapeutic agent for the treatment of hedgehog (Hh)-driven glioblastoma and is currently being evaluated in preclinical studies. In this paper, a novel and practical synthetic route for CAT3 was firstly demonstrated with 10% overall yield in 11 steps and has been successfully validated for pilot-plant scale preparation. Investigation of the substitution at the 3-position of phenanthrene revealed that the electron-donating functionality can well preserve the S configuration. In particular, the excellent enantiomeric excess of CAT3 (≥99% ee) was achieved by introducing the strongly electron-donating tert-butyldimethylsilyl (TBS) group. The Royal Society of Chemistry 2018-08-17 /pmc/articles/PMC9084470/ /pubmed/35547992 http://dx.doi.org/10.1039/c8ra04511a Text en This journal is © The Royal Society of Chemistry https://creativecommons.org/licenses/by-nc/3.0/
spellingShingle Chemistry
Wang, Ru-Bing
Lv, Hai-Ning
Zhu, Shan-Shan
Ren, Xiao-Dong
Xu, Song
Ma, Shuang-Gang
Liu, Yun-Bao
Qu, Jing
Yu, Shi-Shan
A novel and practical synthesis of CAT3: a phenanthroindolizidine alkaloid with potential in treating glioblastoma
title A novel and practical synthesis of CAT3: a phenanthroindolizidine alkaloid with potential in treating glioblastoma
title_full A novel and practical synthesis of CAT3: a phenanthroindolizidine alkaloid with potential in treating glioblastoma
title_fullStr A novel and practical synthesis of CAT3: a phenanthroindolizidine alkaloid with potential in treating glioblastoma
title_full_unstemmed A novel and practical synthesis of CAT3: a phenanthroindolizidine alkaloid with potential in treating glioblastoma
title_short A novel and practical synthesis of CAT3: a phenanthroindolizidine alkaloid with potential in treating glioblastoma
title_sort novel and practical synthesis of cat3: a phenanthroindolizidine alkaloid with potential in treating glioblastoma
topic Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9084470/
https://www.ncbi.nlm.nih.gov/pubmed/35547992
http://dx.doi.org/10.1039/c8ra04511a
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