Chemistry
Twelve derivatives of tetrandrine and fangchinoline such as HJNO were provided by Dr. Weidong Pan’s group. Tetrandrine was selectively halogenated with NXS (X = Cl, Br) in the presence of TFA to obtain compounds HL-5, HL-6, HL-7 and HL-8 [
23] and nitrified to obtain compound HJNO [
24]. HL-15 was also produced as a major by-product with two nitro groups. The nitro group in HJNO was then efficiently transformed into an amino group by Pd/C in hydrazine hydrate to afford the amino compound, which was added the RCOCl to afford compounds HL-22, HL-24 and HL-27 [
23]. HL-25 were synthesized from the amino compound by adding 4-Methylbenzenesulfonyl chloride in pyridine [
25]. Fangchinoline reacted with benzoyl chloride in THF in the presence of 4-dimethylaminopyridine (DMAP) to afford HL-23 [
26]. Fangchinoline was protected with Bn group, then quaternary ammoniated using BnBr to give HY-2.
HL-15 C38H40N4O10 ESI-MS: m/z 713.7 [M + H]+; 1H NMR (CDCl3, 400 MHz) δ (ppm): 7.42 (1H, s), 7.39 (1H, dd, J = 2.4, 8.4 Hz), 7.15 (1H, dd, J = 2.8, 8.4 Hz), 6.77 (1H, dd, J = 2.4, 8.4 Hz), 6.55 (1H, s), 6.52 (1H, s), 6.30 (1H, dd, J = 2.0, 8.4 Hz), 6.00 (1H, s), 3.99 (3H, s), 3.79 (3H, s), 3.71–3.56 (4H, m), 3.44 (3H, s), 3.26 (1H, m), 3.21 (3H, s), 2.96–2.77 (7H, m), 2.66 (3H, s), 2.47 (2H, m), 2.20 (3H, s); 13C NMR (CDCl3, 100 MHz) δ (ppm): 156.7, 151.5, 149.6148.7, 148.5, 144.4, 142.1, 140.7, 138.1, 133.2, 132.6, 129.3, 128.0, 127.7, 127.4, 122.5, 122.3, 121.3, 121.0, 120.6, 120.1, 112.5, 105.9100.6, 64.2, 61.5, 60.0, 56.1, 55.6, 55.5, 45.0, 43.2, 42.3, 40.8, 40.0, 38.7, 24.6, 20.6.
HY-2 C51H53N2O6 ESI-MS: m/z 790.5 [M + H]+; 1H NMR (CDCl3, 400 MHz) δ (ppm): 7.60 (2H, d, J = 7.2 Hz), 7.40 (2H, m), 7.17 (5H, m), 7.02 (1H, dd, J = 2.4, 8.0 Hz), 6.98 (1H, d, J = 8.4 Hz), 6.90 (1H, d, J = 2.0 Hz), 6.88 (1H, d, J = 4.0 Hz), 6.80 (1H, d, J = 8.4 Hz), 6.65 (1H, s), 6.55 (1H, dd, J = 2.4, 8.0 Hz), 6.53 (1H, s), 6.48 (1H, dd, J = 2.4, 8.0 Hz), 6.33 (1H, d, J = 2.0 Hz), 5.68 (1H, s), 5.34 (1H, d, J = 12.4 Hz), 4.98 (1H, d, J = 10.0 Hz), 4.58 (1H, d, J = 10.8 Hz), 4.41 (1H, d, J = 10.8 Hz), 3.89 (3H, s), 3.80 (3H, s), 3.76 (1H, d, J = 4.8 Hz), 3.50 (3H, m), 3.44 (3H, s), 3.40–2.85 (8H, m), 2.83 (3H, s), 2.76 (2H, m), 2.60 (3H, s); 13C NMR (CDCl3, 100 MHz) δ (ppm): 153.7, 153.0, 149.8, 148.1, 147.8, 146.9, 142.2, 137.5, 136.5, 135.6, 133.2, 133.2, 132.0, 131.1, 130.4, 130.4, 128.8, 128.8, 128.4, 128.4, 128.1, 128.1, 128.0, 128.0, 127.5, 124.3, 123.2, 122.4, 122.3, 119.6, 116.0, 112.7, 112.3, 112.1, 106.1, 74.9, 64.5, 64.2, 64.1, 56.2, 56.1, 55.8, 54.9, 51.1, 45.4, 42.3, 40.5, 40.0, 29.8, 24.9, 24.0.