Synthesis of Conformationally Liberated Yohimbine Analogues and Evaluation of Cytotoxic Activity

A modular synthetic approach to strategically unique structural analogues of the alkaloid yohimbine is reported. The overall synthetic strategy couples the transition-metalcatalyzed 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).

Automated summary

A synthetic approach was reported to generate unique structural analogues of the alkaloid yohimbine, with one compound demonstrating increased cytotoxicity against gastric cancer cells.