Cargando…

Ready access to 7,8-dihydroindolo[2,3-d][1]benzazepine-6(5H)-one scaffold and analogues via early-stage Fischer ring-closure reaction

Paullone isomers are known as inhibitors of tubulin polymerase and cyclin dependent kinases (Cdks), which are potential targets for cancer chemotherapy. Herein we report an efficient and clean pathway to the fourth isomer, which remained elusive so far, namely 7,8-dihydroindolo[2,3-d][1]benzazepin-6...

Descripción completa

Detalles Bibliográficos
Autores principales: Kuznetcova, Irina, Bacher, Felix, Vegh, Daniel, Chuang, Hsiang-Yu, Arion, Vladimir B
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Beilstein-Institut 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8805037/
https://www.ncbi.nlm.nih.gov/pubmed/35140815
http://dx.doi.org/10.3762/bjoc.18.15
_version_ 1784643164273901568
author Kuznetcova, Irina
Bacher, Felix
Vegh, Daniel
Chuang, Hsiang-Yu
Arion, Vladimir B
author_facet Kuznetcova, Irina
Bacher, Felix
Vegh, Daniel
Chuang, Hsiang-Yu
Arion, Vladimir B
author_sort Kuznetcova, Irina
collection PubMed
description Paullone isomers are known as inhibitors of tubulin polymerase and cyclin dependent kinases (Cdks), which are potential targets for cancer chemotherapy. Herein we report an efficient and clean pathway to the fourth isomer, which remained elusive so far, namely 7,8-dihydroindolo[2,3-d][1]benzazepin-6(5H)-one. Moreover, we demonstrate the generality of our pathway by synthesizing two closely related analogues, one containing a bromo substituent and the other one incorporating an 8-membered instead of a 7-membered ring. The key transformation in this four-step synthesis, with an overall yield of 29%, is the Fischer indole reaction of 2-nitrophenylacetyl acetoacetate with 1-benzyl-1-phenylhydrazine in acetic acid that delivers methyl 2-(1-benzyl-3-(2-nitrophenyl)-1H-indol-2-yl)acetate in 55% yield.
format Online
Article
Text
id pubmed-8805037
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Beilstein-Institut
record_format MEDLINE/PubMed
spelling pubmed-88050372022-02-08 Ready access to 7,8-dihydroindolo[2,3-d][1]benzazepine-6(5H)-one scaffold and analogues via early-stage Fischer ring-closure reaction Kuznetcova, Irina Bacher, Felix Vegh, Daniel Chuang, Hsiang-Yu Arion, Vladimir B Beilstein J Org Chem Full Research Paper Paullone isomers are known as inhibitors of tubulin polymerase and cyclin dependent kinases (Cdks), which are potential targets for cancer chemotherapy. Herein we report an efficient and clean pathway to the fourth isomer, which remained elusive so far, namely 7,8-dihydroindolo[2,3-d][1]benzazepin-6(5H)-one. Moreover, we demonstrate the generality of our pathway by synthesizing two closely related analogues, one containing a bromo substituent and the other one incorporating an 8-membered instead of a 7-membered ring. The key transformation in this four-step synthesis, with an overall yield of 29%, is the Fischer indole reaction of 2-nitrophenylacetyl acetoacetate with 1-benzyl-1-phenylhydrazine in acetic acid that delivers methyl 2-(1-benzyl-3-(2-nitrophenyl)-1H-indol-2-yl)acetate in 55% yield. Beilstein-Institut 2022-01-26 /pmc/articles/PMC8805037/ /pubmed/35140815 http://dx.doi.org/10.3762/bjoc.18.15 Text en Copyright © 2022, Kuznetcova et al. https://creativecommons.org/licenses/by/4.0/This is an open access article licensed under the terms of the Beilstein-Institut Open Access License Agreement (https://www.beilstein-journals.org/bjoc/terms/terms), which is identical to the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0 (https://creativecommons.org/licenses/by/4.0/) ). The reuse of material under this license requires that the author(s), source and license are credited. Third-party material in this article could be subject to other licenses (typically indicated in the credit line), and in this case, users are required to obtain permission from the license holder to reuse the material.
spellingShingle Full Research Paper
Kuznetcova, Irina
Bacher, Felix
Vegh, Daniel
Chuang, Hsiang-Yu
Arion, Vladimir B
Ready access to 7,8-dihydroindolo[2,3-d][1]benzazepine-6(5H)-one scaffold and analogues via early-stage Fischer ring-closure reaction
title Ready access to 7,8-dihydroindolo[2,3-d][1]benzazepine-6(5H)-one scaffold and analogues via early-stage Fischer ring-closure reaction
title_full Ready access to 7,8-dihydroindolo[2,3-d][1]benzazepine-6(5H)-one scaffold and analogues via early-stage Fischer ring-closure reaction
title_fullStr Ready access to 7,8-dihydroindolo[2,3-d][1]benzazepine-6(5H)-one scaffold and analogues via early-stage Fischer ring-closure reaction
title_full_unstemmed Ready access to 7,8-dihydroindolo[2,3-d][1]benzazepine-6(5H)-one scaffold and analogues via early-stage Fischer ring-closure reaction
title_short Ready access to 7,8-dihydroindolo[2,3-d][1]benzazepine-6(5H)-one scaffold and analogues via early-stage Fischer ring-closure reaction
title_sort ready access to 7,8-dihydroindolo[2,3-d][1]benzazepine-6(5h)-one scaffold and analogues via early-stage fischer ring-closure reaction
topic Full Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8805037/
https://www.ncbi.nlm.nih.gov/pubmed/35140815
http://dx.doi.org/10.3762/bjoc.18.15
work_keys_str_mv AT kuznetcovairina readyaccessto78dihydroindolo23d1benzazepine65honescaffoldandanaloguesviaearlystagefischerringclosurereaction
AT bacherfelix readyaccessto78dihydroindolo23d1benzazepine65honescaffoldandanaloguesviaearlystagefischerringclosurereaction
AT veghdaniel readyaccessto78dihydroindolo23d1benzazepine65honescaffoldandanaloguesviaearlystagefischerringclosurereaction
AT chuanghsiangyu readyaccessto78dihydroindolo23d1benzazepine65honescaffoldandanaloguesviaearlystagefischerringclosurereaction
AT arionvladimirb readyaccessto78dihydroindolo23d1benzazepine65honescaffoldandanaloguesviaearlystagefischerringclosurereaction