posted on 2021-07-13, 19:44authored byHan Yang, Michal Poznik, Shaojian Tang, Peng Xue, Lidong Du, Chenlu Liu, Xiaochuan Chen, Jason J. Chruma
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).