Title : Application of a new generation of triazine-based coupling reagent in medicinal chemistry
Abstract:
Amide bond formation is an important transformation in organic synthesis. These bonds are often present in many active derivatives characterized by a variety of pharmacological activities, e.g. anti-inflammatory, analgesic, antimicrobial or anticancer. The amide group is also a useful intermediate for the synthesis of various biologically active molecules.
Several methods of amide formation have been developed recently. One method is the rhodium-catalyzed amidation of benzoic acids with isocyanates by activation/functionalization of the C-H bond, followed by decarboxylation. The use of rhodium (III) also allows the formation of amides from isocyanates and anilide or enamide. Another method is the synthesis of thioamides from aromatic carboxylic acids and isothiocyanates, which is mediated by palladium. The formation of an amide from a carboxylic acid and an isothiocyanate also occurs under high-temperature conditions in the range 160-170°C, but the yield is low in many cases due to the decomposition of the isothiocyanates at high temperature. The formation of amides from amines and carboxylic acids is also used under thermal and microwave conditions, but, although the catalyst-free approach is practical in many cases, the range of substrates is quite limited. In fact, the formation of carboxamides from carboxylic acids requires the initial activation of the carboxyl group.
Here we presented efficient coupling reagent, which was primarily designed for the synthesis of peptides and then used by us to obtain new active benzamide compounds. It is triazine-based molecule (4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium tetrafluoroborate) aimed to work according to the concept of creating “superactive esters”. This reagent was successfully used for synthesis of dipeptides in 80-100% yield and with high enantiomeric purity. It was therefore applied to the solid phase synthesis of benzene analogues of distamycin, obtaining the expected products in good yields. This reactant has great potential and can find wide application in many syntheses of both peptide and amide bonds.
Audience Take Away:
- The results presented enrich the knowledge of the directions of development of medicinal chemistry and methods of obtaining new active substances.
- The audience will be able to broaden their knowledge of a new compound with interesting activities.
- This research may inspire other scientists to extend their research in new directions, e.g. synthetic chemists to use this substance in their synthetic work.
