Studies on stereoselective approaches to β-carboline derivatives

Abstract

Transformation of β-carboline derivatives into optically active entities were studied and the de and ee values of the resulted compounds were detected.

Synthesis and Antiviral and Fungicidal Activity Evaluation of β-Carboline, Dihydro-β-carboline, Tetrahydro-β-carboline Alkaloids, and Their Derivatives

“…The resulting solution was extracted with dichloromethane (3 × 100 mL), and the combined organic phase was washed with brine (200 mL), dried over anhydrous Na 2 SO 4 , filtered, concentrated in vacuo, and then purified by flash chromatography on silica gel using dichloromethane and methanol (v/v = 5:1) as eluent to give tetrahydroharmane as a brown solid (2.53 g, 62%): mp = 173− 175 °C (lit. 19 Synthesis of Quaternary Ammonium Salts 1. To a solution of harmine (0.50 g, 2.36 mmol) in ethyl acetate (120 mL) was added benzyl bromide (0.48 g, 2.83 mmol), and the mixture was heated at reflux for 12 h. Then the mixture was cooled and filtered, and the filter cake was washed with ethyl acetate and dried to give 1 as a white solid (0.67 g, 74%): mp = 276−277 °C; (m, 3H, Ar−H), 7.23 (d, 3 J HH = 7.2 Hz, 2H, Ar−H), 7.12 (d, 4 J HH = 1.0 Hz, 1H, Ar−H), 7.08 (dd, 3 J HH = 8.8 Hz, 4 J HH = 1.0 Hz, 1H, Ar−H), 5.98 (s, 2H, CH 2 ), 3.95 (s, 3H, OCH 3 ), 2.98 (s, 3H, CH 3 ).…”

“…To a solution of 40% aqueous solution of acetaldehyde (8.1 mL, 43.75 mmol) in water (250 mL) was added concentrated H 2 SO 4 (5 drops), the mixture was stirred at room temperature for 0.5 h. Then tryptamine (3.50 g, 21.88 mmol) was added, and the mixture was heated at reflux for 7 h. The mixture was adjusted to pH 10 with an aqueous solution of NaOH after it was cooled to room temperature. The resulting solution was extracted with dichloromethane (3 × 100 mL), and the combined organic phase was washed with brine (200 mL), dried over anhydrous Na 2 SO 4 , filtered, concentrated in vacuo, and then purified by flash chromatography on silica gel using dichloromethane and methanol (v/v = 5:1) as eluent to give tetrahydroharmane as a brown solid (2.53 g, 62%): mp = 173–175 °C (lit . mp = 177–178 °C); 1 H NMR (400 MHz, DMSO- d 6 ) δ 10.68 (s, 1H, NH), 7.35 (d, 3 J HH = 8.0 Hz, 1H, Ar–H), 7.27 (d, 3 J HH = 8.0 Hz, 1H, Ar–H), 6.98–7.02 (m, 1H, Ar–H), 6.91–6.95 (m, 1H, Ar–H), 3.99–4.04 (m, 1H, CHNH), 3.33 (s, 1H, CHNH), 3.14–3.19 (m, 1H, CH 2 NH), 2.81–2.87 (m, 1H, CH 2 NH), 2.51–2.62 (m, 2H, CH 2 CH 2 ), 1.36 (d, 3 J HH = 6.8 Hz, 3H, CH 3 CH); HRMS (ESI) calcd for C 12 H 15 N 2 (M + H) + 187.1230, found 187.1231.…”

“…Synthesis of (E)-3-(1-Methyl-9H-pyrido [3,4-b]indol-3-yl)acrylic acid (19). To a solution of aldehyde 18 (0.45 g, 2.14 mmol) and piperidine (3 drops) in pyridine was added malonic acid (0.33 g, 3.21 mmol), and the reaction mixture was heated at 120 °C for 4 h. Then the mixture was concentrated in vacuo, water was added (50 mL), the pH was adjusted to 11−12 with an aqueous solution of NaOH, and then the mixture was extracted with diethyl ether.…”

Synthesis and Fungicidal Activity of β-Carboline Alkaloids and Their Derivatives

“…All these compounds were characterized by their melting point, mass, infrared, IR, and 1 H-NMR spectra, which confirmed the proposed structures of the new compounds. Tryptophan, which has an electron-rich indole ring, was used as the parent material when applying Pictet–Spengler or Bischler–Napieralski reactions [25] with a variety of aromatic aldehyde cyclization to give tetrahydrocarboline compounds, then oxidizing to obtain β-carboline compounds by using DMF as a solvent and KMnO 4 as an oxidant. Pictet–Spengler reactions that used acetic acid as the catalyzed solvent produced a reaction that was refluxed at 80 °C to obtain a higher yield (above 80%) of tetrahydro-β-carboline compounds.…”

Synthesis of Racemic and Enantiopure Forms of β-Carboline Alkaloid Brevicolline

“…An analytical sample was recrystallized from a mixture of EtOH-H 2 O; yield: 17.88 g (97%); pale yellow crystals; mp 181-184 °C (EtOH-H 2 O) (Lit. 18 mp 177-178 °C). IR (KBr): 3421, 3052, 1506, 1342, 1217, 1186, 884, 738 cm -1 .…”