Synthesis of isoquinoline alkaloid derivatives from eugenol

Abstract

547.913+547.94+547.833.3 E. S. Limanskii, and M. I. VakhrinAlkylation under phase-transfer catalysis conditions (18-crown-6/KOH) of eugenol was used for cyclocondensation with nitriles (Ritter reaction), the products of which were isoquinoline derivatives.Eugenol (1, 4-allyl-2-methoxyphenol) is the main constituent of essential oil from Syzygium aromaticum (Eugenia caryophyllata) (Myrtaceae), Camelia sasanqua (Theaceae), certain basil species (Ocimum) (Lamiaceae), and other plants [1,2].Various isoquinoline derivatives, many of which can be viewed as synthetic alkaloid analogs, were prepared earlier by cyclocondensation of nitriles with dialkylbenzylcarbinols (Ritter reaction) [3]. The capability for this type of cyclocondensation involving instead of a carbinol 3,4-dimethoxy-and 3,4-methylenedioxyallylbenzenes, which are very similar to eugenol, was demonstrated in classical seminal studies [4,5]. The goal of the present study was to use in analogous syntheses eugenol derivatives and nitriles that were verified by us earlier in reactions with carbinols.Syntheses with a protected phenol hydroxyl were carried out first. The studies showed that the eugenol hydroxyl can be alkylated practically quantitatively under phase-transfer catalysis conditions using 18-crown-6/KOH. Alkylation of 1 by iodomethane or iodoethane formed the corresponding ethers 2 and 3, which were used without further purification in the next step of the Ritter cyclocondensation. Use of hydrogen cyanide [6], acetonitrile [7], and homoveratryl nitrile instead of benzylcyanide [8], chloroacetonitrile [9], and 3-cyanocoumarin [10] as the nitrile component formed the corresponding 3,4-dihydroisoquinolines 4-8. By analogy, reaction of allylbenzenes 2 and 3 with cyanoacetic acid amide produced amides 9 and 10 [11]. The fact that the cyclization occurred without protecting the phenol hydroxyl was interesting. The reaction of eugenol with cyanoacetamide gave enaminoamide 11. Me H 8 5 4 1 a b MeO R 1 O NH Me H O NH 2 2, 3 4 -8 c c 9 -114: R 1 = Et, R 2 = H; 5: R 1 = R 2 = Me 6: R 1 = Me, R 2 = 3,4-dimethoxybenzyl; 7: R 1 = Me, R 2 = CH 2 Cl 8: R 1 = Me, R 2 = 3-coumarinyl; 2, 9: R 1 = Me; 3, 10: R 1 = Et; 11: R 1 = H a. R 1 I, 18-crown-6/KOH; b. R 2 CN; c. NCCH 2 C(O)NH 2

Kopling Oksidatif Eugenol Menggunakan Ekstrak Enzim Peroksidase dari Akar Tanaman Sawi Hijau serta Uji Bioaktivitasnya

“…Senyawa tersebut telah dilaporkan memiliki beberapa aktivitas biologi seperti antijamur (Wang, Zhang, Chen, Fan, & Shi, 2010), antibakteri (Catherine, Deepika, & Negi, 2012), antioksidan (Mahboub & Memmou, 2015;Nam & Kim, 2013) dan antikanker (Abdel-Hameed et al, 2014;Yoo et al, 2005). Pada dekade terakhir, modifikasi eugenol dilakukan dengan 79 tujuan mensintesis senyawa turunan eugenol dengan struktur molekul baru dan aktivitas biologi yang semakin beragam (Hidalgo et al, 2009;Mikhailovskii, Surikova, Limanskii, & Vakhrin, 2012;Sadeghian, Seyedi, Saberi, Arghiari, & Riazi, 2008). Salah satu tipe reaksi organik untuk memodifikasi senyawa fenolik seperti fenol, eugenol, isoeugenol, katekol, guaiakol dan timol adalah kopling oksidatif dengan bantuan katalis kimia (Barve et al, 2015) maupun biokatalis (Cheng & Harper Jr, 2012).…”