Cargando…

Enantioselective total synthesis of (–)-colchicine, (+)-demecolcinone and metacolchicine: determination of the absolute configurations of the latter two alkaloids

Here, we describe a concise, enantioselective, and scalable synthesis of (–)-colchicine (9.2% overall yield, >99% ee). Moreover, we have also achieved the first syntheses of (+)-demecolcinone and metacolchicine, and determined their absolute configurations. The challenging tricyclic 6-7-7 core of...

Descripción completa

Detalles Bibliográficos
Autores principales: Chen, Bo, Liu, Xin, Hu, Ya-Jian, Zhang, Dong-Mei, Deng, Lijuan, Lu, Jieyu, Min, Long, Ye, Wen-Cai, Li, Chuang-Chuang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Royal Society of Chemistry 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5607857/
https://www.ncbi.nlm.nih.gov/pubmed/28959419
http://dx.doi.org/10.1039/c7sc01341h
_version_ 1783265354158440448
author Chen, Bo
Liu, Xin
Hu, Ya-Jian
Zhang, Dong-Mei
Deng, Lijuan
Lu, Jieyu
Min, Long
Ye, Wen-Cai
Li, Chuang-Chuang
author_facet Chen, Bo
Liu, Xin
Hu, Ya-Jian
Zhang, Dong-Mei
Deng, Lijuan
Lu, Jieyu
Min, Long
Ye, Wen-Cai
Li, Chuang-Chuang
author_sort Chen, Bo
collection PubMed
description Here, we describe a concise, enantioselective, and scalable synthesis of (–)-colchicine (9.2% overall yield, >99% ee). Moreover, we have also achieved the first syntheses of (+)-demecolcinone and metacolchicine, and determined their absolute configurations. The challenging tricyclic 6-7-7 core of colchicinoids was efficiently introduced using an intramolecular oxidopyrylium-mediated [5 + 2] cycloaddition reaction. Notably, the synthesized colchicinoid 23 exhibited potent inhibitory activity toward the cell growth of human cancer cell lines (IC(50) = ∼3.0 nM), and greater inhibitory activity towards microtubule assembly than colchicine, making it a promising lead in the search for novel anticancer agents.
format Online
Article
Text
id pubmed-5607857
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher Royal Society of Chemistry
record_format MEDLINE/PubMed
spelling pubmed-56078572017-09-28 Enantioselective total synthesis of (–)-colchicine, (+)-demecolcinone and metacolchicine: determination of the absolute configurations of the latter two alkaloids Chen, Bo Liu, Xin Hu, Ya-Jian Zhang, Dong-Mei Deng, Lijuan Lu, Jieyu Min, Long Ye, Wen-Cai Li, Chuang-Chuang Chem Sci Chemistry Here, we describe a concise, enantioselective, and scalable synthesis of (–)-colchicine (9.2% overall yield, >99% ee). Moreover, we have also achieved the first syntheses of (+)-demecolcinone and metacolchicine, and determined their absolute configurations. The challenging tricyclic 6-7-7 core of colchicinoids was efficiently introduced using an intramolecular oxidopyrylium-mediated [5 + 2] cycloaddition reaction. Notably, the synthesized colchicinoid 23 exhibited potent inhibitory activity toward the cell growth of human cancer cell lines (IC(50) = ∼3.0 nM), and greater inhibitory activity towards microtubule assembly than colchicine, making it a promising lead in the search for novel anticancer agents. Royal Society of Chemistry 2017-07-01 2017-05-05 /pmc/articles/PMC5607857/ /pubmed/28959419 http://dx.doi.org/10.1039/c7sc01341h Text en This journal is © The Royal Society of Chemistry 2017 http://creativecommons.org/licenses/by/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution 3.0 Unported License (http://creativecommons.org/licenses/by/3.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Chemistry
Chen, Bo
Liu, Xin
Hu, Ya-Jian
Zhang, Dong-Mei
Deng, Lijuan
Lu, Jieyu
Min, Long
Ye, Wen-Cai
Li, Chuang-Chuang
Enantioselective total synthesis of (–)-colchicine, (+)-demecolcinone and metacolchicine: determination of the absolute configurations of the latter two alkaloids
title Enantioselective total synthesis of (–)-colchicine, (+)-demecolcinone and metacolchicine: determination of the absolute configurations of the latter two alkaloids
title_full Enantioselective total synthesis of (–)-colchicine, (+)-demecolcinone and metacolchicine: determination of the absolute configurations of the latter two alkaloids
title_fullStr Enantioselective total synthesis of (–)-colchicine, (+)-demecolcinone and metacolchicine: determination of the absolute configurations of the latter two alkaloids
title_full_unstemmed Enantioselective total synthesis of (–)-colchicine, (+)-demecolcinone and metacolchicine: determination of the absolute configurations of the latter two alkaloids
title_short Enantioselective total synthesis of (–)-colchicine, (+)-demecolcinone and metacolchicine: determination of the absolute configurations of the latter two alkaloids
title_sort enantioselective total synthesis of (–)-colchicine, (+)-demecolcinone and metacolchicine: determination of the absolute configurations of the latter two alkaloids
topic Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5607857/
https://www.ncbi.nlm.nih.gov/pubmed/28959419
http://dx.doi.org/10.1039/c7sc01341h
work_keys_str_mv AT chenbo enantioselectivetotalsynthesisofcolchicinedemecolcinoneandmetacolchicinedeterminationoftheabsoluteconfigurationsofthelattertwoalkaloids
AT liuxin enantioselectivetotalsynthesisofcolchicinedemecolcinoneandmetacolchicinedeterminationoftheabsoluteconfigurationsofthelattertwoalkaloids
AT huyajian enantioselectivetotalsynthesisofcolchicinedemecolcinoneandmetacolchicinedeterminationoftheabsoluteconfigurationsofthelattertwoalkaloids
AT zhangdongmei enantioselectivetotalsynthesisofcolchicinedemecolcinoneandmetacolchicinedeterminationoftheabsoluteconfigurationsofthelattertwoalkaloids
AT denglijuan enantioselectivetotalsynthesisofcolchicinedemecolcinoneandmetacolchicinedeterminationoftheabsoluteconfigurationsofthelattertwoalkaloids
AT lujieyu enantioselectivetotalsynthesisofcolchicinedemecolcinoneandmetacolchicinedeterminationoftheabsoluteconfigurationsofthelattertwoalkaloids
AT minlong enantioselectivetotalsynthesisofcolchicinedemecolcinoneandmetacolchicinedeterminationoftheabsoluteconfigurationsofthelattertwoalkaloids
AT yewencai enantioselectivetotalsynthesisofcolchicinedemecolcinoneandmetacolchicinedeterminationoftheabsoluteconfigurationsofthelattertwoalkaloids
AT lichuangchuang enantioselectivetotalsynthesisofcolchicinedemecolcinoneandmetacolchicinedeterminationoftheabsoluteconfigurationsofthelattertwoalkaloids