ABSTRACT
The Pictet-Spengler reaction, using polyethylene glycol immobilized tryptophan ester with a variety of ketones, was achieved by refluxing condition in acidic chloroform. The linear as well as cyclic ketones were employed. All the ketones were reacted within 6-8 h to furnish soluble polymer-supported tetrahydro-ß-carboline in good yields. Further expansion at N-terminus of tetrahydro-ß-carbolines was achieved through a reaction with chloroacetyl chloride. Finally, the 2,5-diketopiperazine skeleton was constructed over a ß-carboline by amination of the resulting N-chloroacetamides and subsequent intramolecular cyclization leading to cleavage of the polymer; constitutes a traceless synthesis of tetracyclic molecular architecture. Significantly, this strategy affords a straightforward and efficient approach for the construction of biological promising molecules with high purity and good yields.
Subject(s)
Carbolines/chemical synthesis , Combinatorial Chemistry Techniques , Diketopiperazines/chemistry , Polymers/chemistry , Amines/chemistry , Carbolines/chemistry , Ketones/chemistry , Models, Chemical , SolubilityABSTRACT
Pharmaceutically interesting, angular bis-benzimidazoles with three appendages have been synthesized successfully through a diversity-oriented approach with soluble support under microwave irradiation. Polymer immobilized o-phenylenediamine was selectively N-acylated with 2-chloro-3-nitrobenzoic acid in a primary aromatic amino moiety. The obtained amide was cyclized to benzimidazole in an acidic condition, and subsequently nucleophilic aromatic substitution with different amines was performed. Successive reduction, cyclization with various aldehydes and activated isothiocyanates yielded angular biheterocyclic benzimidazoles in good quantities. Reaction progress on polymer support was precisely monitored using the conventional proton NMR spectroscopy. Preliminary screening results showed some of these interesting compounds exhibited moderately to good inhibition against vascular endothelial growth factor receptor 3 (VEGFR-3), which is related to invasion and migration of cancer cells.
