SINTESIS 2,5–bis(4’–HIDROKSI–5’–KLORO–3’–METOKSIBENZILIDIN) SIKLOPENTANON DAN UJI AKTIVITASNYA SEBAGAI ANTIOKSIDAN

warsi, Dr. Sardjiman, M.S., Apt.,

2013 | Tesis | S2 Ilmu Farmasi

Telah dilakukan penelitian untuk memperoleh senyawa analog kurkumin dengan modifikasi substituen –Cl pada inti aromatiknya, yaitu –bis(4’– hidroksi–5’–kloro–3’–metoksibenzilidin)siklopentanon. Senyawa ini disintesis dengan mengkondensasikan antara siklopentanon dengan vanilin terklorinasi (4– hidroksi–5–kloro–3–metoksibenzaldehid). Senyawa tersebut telah dilakukan identifikasi strukturnya. Telah pula diteliti aktivitasnya sebagai antioksidan dengan metode penangkap radikal DPPH (1,1–difenil–2–pikrilhidrazil) dan 􀈕- karoten–linoleat. katalis AlCl Reaksi klorinasi vanilin dilakukan dengan gas Cl2 yang merupakan hasil reaksi antara kaporit dan asam klorida pekat. Reaksi berlangsung pada temperatur 35ºC selama 30 menit, dalam 3 dan THF sebagai pelarut, dihasilkan 4– hidroksi–5–kloro–3–metoksibenzaldehid yang berwarna kuning. Rendemen rata– rata yang diperoleh sebesar 40,54 % dan jarak leburnya 163,3–164,8ºC. Senyawa 4–hidroksi–5–kloro–3–metoksibenzaldehid kemudian dikondensasikan dengan siklopentanon membentuk 2,5–bis(4’–hidroksi–5’–kloro–3’–metoksibenzilidin) siklopentanon, yang berwarna hijau–kuning. Reaksi kondensasi berlangsung pada suhu kamar, selama 4 jam, dalam suasana asam, THF sebagai pelarut dan pendiaman selama 6 hari. Rendemen rata–rata yang diperoleh sebesar 49,77 % dan jarak leburnya 268,0–270,0ºC. Kemurnian senyawa hasil sintesis ditentukan dengan kromatografi lapis tipis serta kromatografi cair kinerja tinggi. Elusidasi struktur senyawa–senyawa hasil sintesis menggunakan teknik spektroskopi, meliputi inframerah, resonansi megnetik inti proton, resonansi magnetik inti karbon dan spektrometri massa. – Aktivitas antioksidan produk sintesis ditentukan dengan metode penangkap radikal DPPH dan absorbansinya diukur di spektrofotometer UV–Vis pada 􀈜 maksimum 517 nm. Senyawa hasil sintesis memiliki aktivitas penangkap radikal DPPH dengan nilai IC50 184,23 􀈝M, potensinya lebih rendah dibandingkan dengan PGV–0 (IC50 26,76 􀈝M) serta kurkumin (IC50 13,69 􀈝M). Potensi antioksidan produk sintesis juga ditentukan berdasarkan penghambatan degradasi 􀈕 karoten oleh radikal asam linoleat dan absorbansinya diukur dengan spektrofotometer UV–Vis pada 􀈜 maksimum 450 nm. Hasil pengujian dengan metode ini diperoleh nilai EC50 sebesar 23,04 􀈝M. Potensi antioksidan sampel lebih besar dibandingkan dengan kurkumin (EC50 25,86 􀈝M) dan PGV–0 (EC50 32,15 􀈝M).

A study was performed to obtain a curcumin analogue compound which ha –Cl substituent in the aromatic ring i.e. 2,5–bis(5’–chloro–4’–hydroxy–3’– methoxybenzylidene)cyclopentanone. The synthesis of this compound was carried out by condensation of cyclopentanone with chlorinated vanilin (5–chloro–4– hydroxy–3–methoxybenzaldehyde). This compound has been identified. Its activity as an antioxidant using DPPH (1,1–diphenyl–2–picrylhydrazyl) radical scavenging and the 􀈕-carotene–linoleic acid methods have been investigated. Th Chlorination reaction of vanillin performed using Cl2 gas, which produced by reaction of kaporit with concentrated hydrochloric acid. e reaction occured at 35ºC for 30 minutes, with the AlCl3 as a catalyst and THF as the solvent. It produced a yellow compound of 5–chloro–4–hydroxy–3–methoxybenzaldehyde. The average yield was 40.54 % and the melting point was 163.3–164.8ºC. Then, 5–chloro–4–hydroxy–3–methoxybenzaldehyde was condensed with cyclopen- tanone to form a green–yellow compound of 2,5–bis(5’–chloro–4’ Hydroxyl – 3’– methoxybenzylidene)cyclopentanone. This condensation reaction occured at room temperature for 4 hours, under acidic conditions and THF as the solvent. The reaction mixture was set aside for 6 days. The average yield is 49,77 % and the melting point of 268.0–270.0ºC. The purity of the synthesized compounds were determined by Thin Layer Chromatography and High Performance Liquid Chromatography. The structure elucidation of this synthesized compounds have been performed using spectroscopy techniques, including infrared, nuclear magnetic resonance proton, nuclear magnetic resonance carbon and mass spectrometry. – The antioxidant activity of synthesized product was determined by DPPH radical scavenging method and the absorbance was measured by the UV Vis spectrophotometer at 􀈜max of 517 nm. The synthesized compound showed the activity of DPPH radical scavenging metode (IC50 184.23 􀈝M). Its potency as an antioxidant was lower than PGV–0 (IC50 26.76 􀈝M) and curcumin (IC50 13.69 􀈝M). The potency of antioxidant activity of synthesized product was also determined based on inhibition of the 􀈕-carotene bleaching by the linoleic acid radical and the absorbance was measured by the UV–Vis spectrophotometer at 􀈜max of 450 nm. The result of this method obtained EC50 value of 23.04 􀈝M. The antioxidant potency of the sample was more potent than those curcumin (EC50 25.86 􀈝M) and PGV–0 (EC50 32.15 􀈝M).

Kata Kunci : analog kurkumin, vanilin terklorinasi, antioksidan, DPPH, 􀈕-karoten–linoleat