Synthesis of Trans Electron-Rich Substituted Isoflavans from Isoflavanol

IVAN RANGGA PRATAMA, Dr. Tutik Dwi Wahyuningsih, M.Si.; Dr. Endang Astuti, M.Si.

2018 | Skripsi | S1 KIMIA

Sintesis trans-isoflavan dari isoflavanol, 4-(7-asetoksi-4-hidroksikroman-3-il)fenil asetat dan hidrolisisnya telah dilakukan. Konversi stereoselektif dari trans-isoflavan menjadi cis-isoflavan telah dicoba. Namun, percobaan ini telah terbukti tidak berhasil. Sintesis trans-isoflavan dimulai dengan mereaksikan isoflavanol dengan substituen kaya-elektron, yaitu 3,4,5-trimetoksifenol, 1,3-dimetoksibenzena, atau anisole dengan adanya katalis BF3.OEt2 di dalam diklorometan anhydrous pada suhu ruangan dan atmosfir argon inert selama 3 jam untuk menghasilkan 4-((3S,4S)-7-asetoksi-4-(6-hidroksi-2,3,4-trimetoksifenil)kroman-3-il)fenil asetat (trans-isoflavan 1), 4-((3S,4R)-7-asetoksi-4-(2,4-dimetoksifenil)kroman-3-il) fenil asetat (trans-isoflavan 2), dan 4-((3S,4R)-7-asetoksi-4-(4-metoksifenil)kroman-3-il)fenil asetat (trans-isoflavan 3), secara berurutan. Hidrolisis gugus asetil pada trans-isoflavan menjadi gugus hidroksil dilakukan dengan mereaksikan trans-isoflavan yang telah disintesis dengan kalium hidroksida di dalam metanol, dan kemudian ditambahkan asam asetat untuk menghentikan reaksinya, yang menghasilkan (3S,4S)-4-(6-hidroksi-2,3,4-trimetoksifenil)-3-(4-hidroksifenil)kroman-7-ol (hydroxylated trans-isoflavan 1), (3S,4R)-4-(2,4-dimetoksifenil)-3-(4-hidroksifenil)kroman-7-ol (hydroxylated trans-isoflavan 2), and (3S,4R)-3-(4-hidroksifenil)-4-(4-metoksifenil)kroman-7-ol (hydroxylated trans-isoflavan 3). Dari sintesis trans-isoflavan ditemukan bahwa trans-isoflavan 1, trans-isoflavan 2, dan trans-isoflavan 3 telah berhasil disintesis dengan rendemen sebesar 64,8%, 43,3%, dan 41,6% dari 500 mg bahan dasar isoflavanol. Sedangkan, proses hidrolisisnya telah berhasil menghasilkan hydroxylated trans-isoflavan 1, hydroxylated trans-isoflavan 2, dan hydroxylated trans-isoflavan 3 dengan rendemen sebesar 85 mg (97,0%), 58 mg (94,5%), dan 49 mg (86,9%). Usaha untuk mengubah trans-isoflavan menjadi cis-isoflavan telah gagal dalam tahap oksidasi untuk menghasilkan isoflaven. Maka, reduksi darinya tidak dilakukan.

Synthesis of trans-isoflavans from isoflavanol, 4-(7-acetoxy-4-hydroxy chroman-3-yl)phenyl acetate, and its hydrolysis had been carried out. Then, a stereoselective conversion of the trans-isoflavan into cis-isoflavan had been attempted. However, this was proven to be unsuccessful. The synthesis of trans-isoflavans was done by mixing isoflavanol with the electron-rich substituent, i.e. 3,4,5-trimethoxyphenol, 1,3-dimethoxybenzene or anisole with the presence of BF3.OEt2 in anhydrous dichloromethane (DCM) at room temperature and inert atmosphere of argon for 3 h, to produce 4-((3S,4S)-7-acetoxy-4-(6-hydroxy-2,3,4-trimethoxyphenyl)chroman-3-yl)phenyl acetate (trans-isoflavan 1), 4-((3S,4R)-7-acetoxy-4-(2,4-dimethoxyphenyl)chroman-3-yl) phenyl acetate (trans-isoflavan 2), and 4-((3S,4R)-7-acetoxy-4-(4-methoxy phenyl)chroman-3-yl)phenyl acetate (trans-isoflavan 3), respectively. The hydrolysis of the acetyl ends of the trans-isoflavans into hydroxyl ends was done by mixing each of the synthesised trans-isoflavans with potassium hydroxide in methanol, followed by quenching it in acetic acid, to give out (3S,4S)-4-(6-hydroxy-2,3,4-trimethoxyphenyl)-3-(4-hydroxyphenyl)chroman-7-ol (hydroxylated trans-isoflavan 1), (3S,4R)-4-(2,4-dimethoxyphenyl)-3-(4-hydroxyphenyl)chroman-7-ol (hydroxylated trans-isoflavan 2), and (3S,4R)-3-(4-hydroxyphenyl)-4-(4-methoxyphenyl)chroman-7-ol (hydroxylated trans-isoflavan 3). While the attempt to convert trans-isoflavans into their cis-isoflavans counterparts was done by trying to oxidise the trans-isoflavans into isoflavenes and followed by its reduction by using H2(g) in the presence of Pd/C catalyst to obtain the cis-isoflavans. All the synthesised products were characterised by using 1H- and 13C-NMR, IT-ESI or FT-NSI MS, and FTIR. From the synthesis of trans-isoflavan, it was found that trans-isoflavan 1, trans-isoflavan 2 and trans-isoflavan 3 had been successfully synthesised with the yield of 64.8%, 43.3% and 41.6%, respectively from 500 mg isoflavanol starting material. While its hydrolysis had successfully produced hydroxylated trans-isoflavan 1, hydroxylated trans-isoflavan 2 and hydroxylated trans-isoflavan 3 with the yield of 85 mg (97.0%), 58 mg (94.5%) and 49 mg (86.9%), respectively. The attempt of converting trans-isoflavans into cis-isoflavans had failed in the oxidation to produce isoflavenes. Thus, its reduction was not carried out.

Kata Kunci : synthesis, isoflavan, electron-rich, stereochemistry