SYNTHESIS OF CHALCONE DERIVATIVES WITH VANILLIN PRECURSOR AS PHENOLIC SOURCE AND THEIR ACTIVITY TEST

• Main Author: Jannatu Adni, Mutiara
• Format: Theses
• Language: Indonesia
• Subjects: Kimia
• Online Access: https://digilib.itb.ac.id/gdl/view/75550
• Institution: Institut Teknologi Bandung

Chalcone compounds are one type of flavonoid compound known as open-chain flavonoids that are widely found in nature. Chalcone compounds are produced biosynthetically through the shikimic pathway. Chalcone has a variety of activities, including antioxidant, anticancer, antidiabetic, anti-inflammatory, antibacterial, and antimalarial. The simple structure and the variety of interesting bioactivities of chalcone attract researchers to conduct studies on chalcone. Besides being obtained by isolation, various methods of synthesizing chalcone have been developed, including Claisen-Schmidt condensation, Suzuki coupling, and Heck coupling. Chemically, this compound is an unsaturated ?,?-ketone consisting of two aromatic rings connected by a three-carbon unit. In this study, vanillin was used as a free phenolic source precursor. Vanillin is a natural flavor and fragrance that is widely used in the food industry, so it is easily found on the market and is commercially available. Vanillin is a benzaldehyde derivative that will produces phenolic chalcone. A phenolic chalcone can be synthesized with simple aromatic compounds and easily modified to obtain chalcone-derived compounds. The most widely practiced method of chalcone synthesis is the Claisen-Schmidt condensation method, which involves the condensation of acetophenone and benzaldehyde, with minimal work-up. Basically, the first stage of the reaction is the reaction of acetophenone with a strong base such as KOH, NaOH, or Ba(OH)2 in order to form reactive enolate species. Then benzadehyde is used as an electrophile source to make a chalcone. Hydroxy groups can be the active side in the synthesis of chalcone derivatives, one of which is the reaction with allyl chloride. The allyl group was chosen as the protection group because it is a model of the reaction with allyl cations as in the prenylation reaction. Prenylated flavonoid compounds are also known to be compounds with interesting bioactivity. The allyl ether group formed can then be subjected to Claisen rearrangement to again produce free phenolics. Three chalcone-derived compounds have been successfully synthesized and identified using spectroscopic techniques such as 1H NMR, 13C NMR, and UV-Vis. These compounds were 3-hydroxy-4-methoxychalcone, 4-alloxy-3- methoxychalcone, and 4,4'-dialloxy-3-methoxy-2'-hydroxichalcone. As a comparison of the reactivity of Claisen-Schmidt condensation, the allylation reaction of vanillin and resacetophenone was also carried out. Claisen-Schmidt condensation was then carried out on vanillin with acetophenone to give 3- hydroxy-4-methoxichalcone, and the reaction of 4-aryl vanillin with 4-aryl resacetophenone gave 4,4'-dialyloxy-3-methoxy-2'-hydroxichalcone. In addition, 3-hydroxy-4-methoxichalcone was reacted with allyl chloride to yield 4-allyloxy-3- methoxichalcone. Antioxidant activity tests using the DPPH method on the three chalcone-derived compounds with ascorbic acid as a comparison compound, showed 3-hydroxy-4-methoxychalcone is the most active compound with an IC50 value of 9.97 ppm, followed by 4-allyloxy-3-methoxichalcone with an IC50 value of 44,70 ppm, and 4,4'-dialyloxy-3-methoxy-2'-hydroxichalcone with an IC50 value of 71,72 ppm. The most active compounds were 4-allyloxy-3-methoxichalcone with an IC50 value of 6,97 ppm, 3-hydroxy-4-methoxichalcone with an IC50 value of 10,29 ppm, and 4,4'-dialloxy-3-methoxy-2'-hydroxichalcone with an IC50 value of 72,32 ppm. From the two test methods carried out, it can be seen that the hydroxy group is an important chromophore in antioxidant activity, while the allylation on 4- allyloxy-3-methoxichalcone can increase cytotoxic activity on P-388 murine leukemia cells, and of the allyl resacetophenone skeleton decreases activity.