Dehydroevodiaminehydrochloride

Uses

Dehydroevodiamine hydrochloride is isolated from the leaves of Evodia rutaecarpa[1].

Biological Activity

Dehydroevodiamine is the major alkaloid of Evodia rutaecarpa th at exhibit cardiovascular effects such as bradycardia, hypotension, and vasorelaxation. Dehydroevodiamine potently inhibits hERG channels. Apparently it is a blocker of IKr (rapid delayed rectifier current) with proarrhythmic effects in vitro and in vivo. Dehydroevodiamine ameliorates the spatial memory impairment in the scopolamine-induced amnestic rats. It reduced neurotoxicity and the production of A-induced ROS in primary cortical neurons.

Synthesis

The general procedure for the synthesis of chlorinated dehydrowuzhu bases using 2-(2-(methylamino)benzoyl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-1-one as starting material was as follows: compound 2b was dissolved in dichloromethane followed by addition of an isopropanol solution of 1 M hydrochloric acid (8.0 equiv.). The reaction mixture immediately changed color and was stirred at room temperature for 15 minutes. Upon completion of the reaction, the solvent was removed by vacuum distillation to give the product 2a in the form of quinazolinium directly in quantitative yield without further purification. Thin layer chromatography (TLC) analysis showed Rf = 0.29 (trailing) (silica gel plate, 100% ethyl acetate as unfolding agent). The melting point of the product was 204-206 °C. Nuclear magnetic resonance hydrogen spectroscopy (1H NMR, 400 MHz, CD3OD, 300K) data were as follows: δ= 8.54-8.44 (m, 1H, Ar-HE-cyclic), 8.19-8.09 (m, 2H, Ar-HE-cyclic), 7.90 (dt, J = 8.3,1.0 Hz, 1H, Ar-HA-cyclic), 7.83 (ddd, J = 8.1,6.9,1.3 Hz, 1H, Ar-HE-ring), 7.74-7.67 (m, 1H, Ar-HA-ring), 7.60 (ddd, J = 8.4,6.9,1.1 Hz, 1H, Ar-HA-ring), 7.35 (ddd, J = 8.1,6.9,0.9 Hz, 1H, Ar-HA-ring), 4.69- 4.58 (m, 2H, NCH2CH2), 4.49 (s, 3H, CH3), 3.50-3.40 (m, 2H, NCH2CH2) ppm. (No NH signal was detected in MeOD.) NMR carbon spectra (13C{1H} NMR, 101 MHz, CD3OD, 300K) data were as follows: δ= 159.54 (s, C = O), 151.75 (s, C=N), 143.60 (s, Cquart.), 141.36 (s, Cquart.), 137.90 (s, Ar-C), 133.08 (s, Cquart.), 130.67 (s, Ar-C), 129.86 (s, Ar-C), 129.45 (s, Ar-C ), 125.15 (s, Cquart.), 123.35 (s, Ar-C), 122.57 (s, Ar-C), 121.11 (s, Cquart.), 120.42 (s, Cquart.), 119.28 (s, Ar-C), 114.41 (s, Ar-C), 43.46 (s, NCH2CH2), 41.45 (s, CH3), 20.03 (s, NCH2CH2) ppm. infrared spectra (IR) major absorption peaks: ν= 3287-2308 brw, 1701s, 1608s, 1542s, 1498s, 1455m, 1511m, 1384w, 1365w, 1335s, 1278m , 1255m, 1236w, 1206m, 1167w, 1122w, 1103m, 1049w, 1008w, 966w, 936w, 851w, 768m, 751s, 718w, 675m cm-1. High-performance liquid chromatography (HPLC) analytical conditions: Synergi 4U fusion-RP column (15 × 0.46 cm), water/methanol (30-95%) gradient elution with 0.1% formic acid, flow rate 1.00 mL/min, column temperature 20°C, retention time tR = 4.599 min, purity = 94.99%. Mass spectrometry analysis: calculated value [M]+(C19H16N3O) m/z: 302.13; measured value: 302.15.

References

[1] Haji A, et al. Increased feline cerebral blood flow induced by dehydroevodiamine hydrochloride from Evodia rutaecarpa. J Nat Prod. 1994 Mar;57(3):387-9. DOI:10.1021/np50105a009