Sintesis Prekursor Kalkon Apigenin dari Floroglusinol

Abstract

Apigenin merupakan senyawa flavonoid golongan flavon yang memiliki berbagai aktivitas farmakologis, seperti antioksidan, antiinflamasi, dan antikanker. Isolasi apigenin dari bahan alam umumnya memerlukan banyak tahap pemurnian dan rendemennya rendah sehingga sintesis kimia dapat menjadi alternatif. Salah satu cara sintesis apigenin yang umum melibatkan intermediat kalkon. Penelitian ini bertujuan menyintesis prekursor kalkon apigenin, yaitu 2'-hidroksi-4,4',6'- trimetoksikalkon (HTMC), melalui jalur sintesis tiga tahap dari floroglusinol. Asilasi Friedel–Crafts floroglusinol dengan anhidrida asetat dan katalis BF3Et2O menghasilkan floroasetofenon dengan rendemen 98%. Metilasi floroasetofenon dengan metil tosilat dan basa K2CO3 menghasilkan 2',4'-di-O-metilfloroasetofenon (DMP) dengan rendemen 57%. Struktur kedua produk sintetik ini telah dikonfirmasi dengan NMR proton dan karbon. Kondensasi Claisen–Schmidt DMP dengan anisaldehida dan basa KOH belum berhasil membentuk HTMC.

Apigenin is a flavonoid compound of the flavone group that has various pharmacological activities, such as antioxidant, anti-inflammatory, antimicrobial, neuroprotective, and anticancer. Isolation of apigenin from natural sources generally requires many purification steps and resulting in low yields, making chemical synthesis an alternative. One common synthetic method involves a chalcone intermediate. In this study, 2'-hydroxy-4,4',6'-trimethoxychalcone (HTMC), the chalcone precursor of apigenin, was synthesized from phloroglucinol through three reaction steps. Friedel–Crafts acylation of phloroglucinol with acetic anhydride and BF3Et2O as catalyst, produced phloroacetophenone in 98% yield. Methylation of phloroacetophenone with methyl tosylate and K2CO3 base produced 2',4'-di-O-methylphloroacetophenone (DMP) with a yield of 57%. The structures of these two synthetic products were confirmed by proton and carbon NMR. Claisen–Schmidt condensation of DMP with anisaldehyde and KOH base did not afford HTMC.