Feasible Column Chromatography-Free, Multi-Gram Scale Synthetic Process of VH032 Amine, Which Could Enable Rapid PROTAC Library Construction

[Image: see text] PROTACs represent a promising modality that has gained significant attention for the treatment of cancer, Alzheimer’s disease, and so forth. Due to limited structural information of the POI-PROTAC-E3 ligase ternary complex, the discovery of active PROTACs relies on the screening of...

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Autores principales: Yan, Wei, Pan, Bo-Syong, Shao, Jingwei, Lin, Hui-kuan, Li, Hong-yu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2022
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9352171/
https://www.ncbi.nlm.nih.gov/pubmed/35936457
http://dx.doi.org/10.1021/acsomega.2c00245
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author Yan, Wei
Pan, Bo-Syong
Shao, Jingwei
Lin, Hui-kuan
Li, Hong-yu
author_facet Yan, Wei
Pan, Bo-Syong
Shao, Jingwei
Lin, Hui-kuan
Li, Hong-yu
author_sort Yan, Wei
collection PubMed
description [Image: see text] PROTACs represent a promising modality that has gained significant attention for the treatment of cancer, Alzheimer’s disease, and so forth. Due to limited structural information of the POI-PROTAC-E3 ligase ternary complex, the discovery of active PROTACs relies on the screening of diversity-oriented PROTAC libraries. VH032 amine is a key building block for the synthesis of VHL E3 ligase-based PROTACs. To construct VHL PROTAC libraries rapidly, the availability of VH032 amine is crucial. In this paper, we report a column chromatography-free process which enables the production of 42.5 g of VH032 amine hydrochloride in 65% overall yield with 97% purity in a week.
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spelling pubmed-93521712022-08-05 Feasible Column Chromatography-Free, Multi-Gram Scale Synthetic Process of VH032 Amine, Which Could Enable Rapid PROTAC Library Construction Yan, Wei Pan, Bo-Syong Shao, Jingwei Lin, Hui-kuan Li, Hong-yu ACS Omega [Image: see text] PROTACs represent a promising modality that has gained significant attention for the treatment of cancer, Alzheimer’s disease, and so forth. Due to limited structural information of the POI-PROTAC-E3 ligase ternary complex, the discovery of active PROTACs relies on the screening of diversity-oriented PROTAC libraries. VH032 amine is a key building block for the synthesis of VHL E3 ligase-based PROTACs. To construct VHL PROTAC libraries rapidly, the availability of VH032 amine is crucial. In this paper, we report a column chromatography-free process which enables the production of 42.5 g of VH032 amine hydrochloride in 65% overall yield with 97% purity in a week. American Chemical Society 2022-07-19 /pmc/articles/PMC9352171/ /pubmed/35936457 http://dx.doi.org/10.1021/acsomega.2c00245 Text en © 2022 The Authors. Published by American Chemical Society https://creativecommons.org/licenses/by-nc-nd/4.0/Permits non-commercial access and re-use, provided that author attribution and integrity are maintained; but does not permit creation of adaptations or other derivative works (https://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Yan, Wei
Pan, Bo-Syong
Shao, Jingwei
Lin, Hui-kuan
Li, Hong-yu
Feasible Column Chromatography-Free, Multi-Gram Scale Synthetic Process of VH032 Amine, Which Could Enable Rapid PROTAC Library Construction
title Feasible Column Chromatography-Free, Multi-Gram Scale Synthetic Process of VH032 Amine, Which Could Enable Rapid PROTAC Library Construction
title_full Feasible Column Chromatography-Free, Multi-Gram Scale Synthetic Process of VH032 Amine, Which Could Enable Rapid PROTAC Library Construction
title_fullStr Feasible Column Chromatography-Free, Multi-Gram Scale Synthetic Process of VH032 Amine, Which Could Enable Rapid PROTAC Library Construction
title_full_unstemmed Feasible Column Chromatography-Free, Multi-Gram Scale Synthetic Process of VH032 Amine, Which Could Enable Rapid PROTAC Library Construction
title_short Feasible Column Chromatography-Free, Multi-Gram Scale Synthetic Process of VH032 Amine, Which Could Enable Rapid PROTAC Library Construction
title_sort feasible column chromatography-free, multi-gram scale synthetic process of vh032 amine, which could enable rapid protac library construction
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9352171/
https://www.ncbi.nlm.nih.gov/pubmed/35936457
http://dx.doi.org/10.1021/acsomega.2c00245
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