Synthesis of Conformationally Liberated Yohimbine Analogues and Evaluation of Cytotoxic Activity

[Image: see text] A modular synthetic approach to strategically unique structural analogues of the alkaloid yohimbine is reported. The overall synthetic strategy couples the transition-metal-catalyzed decarboxylative allylation of 2,2-diphenylglycinate imino esters with a scandium triflate-mediated...

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Autores principales: Yang, Han, Poznik, Michal, Tang, Shaojian, Xue, Peng, Du, Lidong, Liu, Chenlu, Chen, Xiaochuan, Chruma, Jason J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2021
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8320076/
https://www.ncbi.nlm.nih.gov/pubmed/34337266
http://dx.doi.org/10.1021/acsomega.1c02784
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author Yang, Han
Poznik, Michal
Tang, Shaojian
Xue, Peng
Du, Lidong
Liu, Chenlu
Chen, Xiaochuan
Chruma, Jason J.
author_facet Yang, Han
Poznik, Michal
Tang, Shaojian
Xue, Peng
Du, Lidong
Liu, Chenlu
Chen, Xiaochuan
Chruma, Jason J.
author_sort Yang, Han
collection PubMed
description [Image: see text] A modular synthetic approach to strategically unique structural analogues of the alkaloid yohimbine is reported. The overall synthetic strategy couples the transition-metal-catalyzed decarboxylative allylation of 2,2-diphenylglycinate imino esters with a scandium triflate-mediated highly endo-selective intramolecular Diels–Alder (IMDA) cycloaddition to generate a small collection of de-rigidified yohimbine analogues lacking the ethylene linkage between the indole and decahydroisoquinoline units. One compound generated in this study contains an unprecedented pentacyclic urea core and appears to demonstrate increased cytotoxicity against the gastric cancer cell line SGC-7901 in comparison to a pancreatic cancer cell line (PATU-8988) and a normal human gastric mucosal cell line (GES-1).
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spelling pubmed-83200762021-07-30 Synthesis of Conformationally Liberated Yohimbine Analogues and Evaluation of Cytotoxic Activity Yang, Han Poznik, Michal Tang, Shaojian Xue, Peng Du, Lidong Liu, Chenlu Chen, Xiaochuan Chruma, Jason J. ACS Omega [Image: see text] A modular synthetic approach to strategically unique structural analogues of the alkaloid yohimbine is reported. The overall synthetic strategy couples the transition-metal-catalyzed decarboxylative allylation of 2,2-diphenylglycinate imino esters with a scandium triflate-mediated highly endo-selective intramolecular Diels–Alder (IMDA) cycloaddition to generate a small collection of de-rigidified yohimbine analogues lacking the ethylene linkage between the indole and decahydroisoquinoline units. One compound generated in this study contains an unprecedented pentacyclic urea core and appears to demonstrate increased cytotoxicity against the gastric cancer cell line SGC-7901 in comparison to a pancreatic cancer cell line (PATU-8988) and a normal human gastric mucosal cell line (GES-1). American Chemical Society 2021-07-13 /pmc/articles/PMC8320076/ /pubmed/34337266 http://dx.doi.org/10.1021/acsomega.1c02784 Text en © 2021 The Authors. Published by American Chemical Society 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 Yang, Han
Poznik, Michal
Tang, Shaojian
Xue, Peng
Du, Lidong
Liu, Chenlu
Chen, Xiaochuan
Chruma, Jason J.
Synthesis of Conformationally Liberated Yohimbine Analogues and Evaluation of Cytotoxic Activity
title Synthesis of Conformationally Liberated Yohimbine Analogues and Evaluation of Cytotoxic Activity
title_full Synthesis of Conformationally Liberated Yohimbine Analogues and Evaluation of Cytotoxic Activity
title_fullStr Synthesis of Conformationally Liberated Yohimbine Analogues and Evaluation of Cytotoxic Activity
title_full_unstemmed Synthesis of Conformationally Liberated Yohimbine Analogues and Evaluation of Cytotoxic Activity
title_short Synthesis of Conformationally Liberated Yohimbine Analogues and Evaluation of Cytotoxic Activity
title_sort synthesis of conformationally liberated yohimbine analogues and evaluation of cytotoxic activity
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8320076/
https://www.ncbi.nlm.nih.gov/pubmed/34337266
http://dx.doi.org/10.1021/acsomega.1c02784
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