构象自由的育亨宾类似物的合成及细胞毒性活性评估。

Synthesis of Conformationally Liberated Yohimbine Analogues and Evaluation of Cytotoxic Activity.

作者信息

Yang Han, Poznik Michal, Tang Shaojian, Xue Peng, Du Lidong, Liu Chenlu, Chen Xiaochuan, Chruma Jason J

机构信息

Key Laboratory of Green Chemistry & Technology (MOE), College of Chemistry and Sino-British Materials Research Institute, College of Physical Sciences & Technology, Sichuan University, Chengdu, Sichuan 610064, P. R. China.

School of Pharmacy, Weifang Medical University, No. 7166, Baotong West Road, Weifang, Shandong 261053, P. R. China.

出版信息

ACS Omega. 2021 Jul 13;6(29):19291-19303. doi: 10.1021/acsomega.1c02784. eCollection 2021 Jul 27.

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).