TUMOR INHIBITORS .42. THALIDASINE, A NOVEL BISBENZYLISOQUINOLINE ALKALOID TUMOR INHIBITOR FROM THALICTRUM DASYCARPUM

Evidence is presented for assignment of structure and configuration 1a to thalidasine, a new alkaloid tumor inhibitor from Thalictrum dasycarpum. Elemental analysis and molecular weight determination by mass spectrometry supported a C39H44N2O7 formula. Functional group analysis and nmr spectral evidence showed the presence of five O-methyl groups and two N-methyl groups. Cleavage in sodium-liquid ammonia afforded L-O-methylarmepavine (2a), L-1-(4’-hydroxybenzyl)-2-methyl-5-hydroxy-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline (3c), L-armepavine (3e), and L-1-(4’-methoxybenzyl)-2-methyl-6,7-dimethoxy-8-hydroxy-1,2,3,4-tetrahydroisoquinoline (2b). Permanganate oxidation of thalidasine yielded 2-methoxydiphenyl ether 4’,5-dicarboxylic acid (17). The mass spectrum of thalidasine showed a base peak corresponding to a doubly charged ion of m/e 213, supporting the unsymmetrical bisbenzylisoquinoline nature of the structure 1a. Thalfoetidine is shown to possess structure 1b, on the basis of evidence which includes interrelation with thalidasine. © 1969, American Chemical Society. All rights reserved.