ABSTRACT
Parthenolide (PTL) strongly inhibits the detyrosination of microtubules and accelerates neuronal growth. In order to access cyclic ether derivatives of PTL, ring-closing metathesis (RCM) was investigated in comparison to intramolecular sulfone alkylation. Incompatibility of RCM with epoxides was found in this setting. Biological evaluation for tubulin carboxypeptidase inhibition indicated that the epoxide is crucial for parthenolide's activity.
Subject(s)
Carboxypeptidases/antagonists & inhibitors , Enzyme Inhibitors/pharmacology , Ether/pharmacology , Microtubules/drug effects , Neurons/drug effects , Sesquiterpenes/pharmacology , Adult , Carboxypeptidases/metabolism , Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/chemistry , Ether/chemical synthesis , Ether/chemistry , Humans , Molecular Structure , Sesquiterpenes/chemical synthesis , Sesquiterpenes/chemistry , Structure-Activity Relationship , Tanacetum parthenium/chemistryABSTRACT
A pyridyl triazole (pyta) modified sucrose ligand was prepared in a seven step synthesis using d-glucose as the protection group for d-fructose and starting from commercially available sucrose. After complexation with Ru(bpy)2Cl2 precursor, the sucrose-conjugated Ru complex of the general formula [Ru(bpy)2(L)]Cl2 was formed. Acidic cleavage of the d-glucose unit led to the first d-fructose conjugated metal complex viad-fructose C6 in literature. Additionally, pyta-modified d-fructose via C1 and the corresponding Ru complex were synthesized. All compounds were analyzed by Rf values, specific rotation, NMR, IR, UV/Vis and fluorescence spectroscopy, mass spectrometry and elemental analysis.