Synthesis, Characterization And Biological Activities Of 2, 5-Disubstituted-1, 3, 4-Thiadiazoles, N-Substituted Dihydrazides And Divalent Glycoclusters

1. A facile one-pot synthesis of 2, 5-disubstituted-1, 3, 4-thiadiazoles and N-substituted dihydrazides was achieved by ultrasonic irradiation and phase transfer catalysis, and seven novel 2, 5-disubstituted-1, 3, 4-thiadiazoles (TM-I-7a～7g) and nine N-substituted dihydrazides (TM-II-8a～8i) were synthesized. This method has the advantages of mild conditions, short time, good yields, convenient, economical and environment friendly. The intermediate acylthiosemicarbazides (6a～6g) were translated into target molecules TM-I-7a～7g without any acidic reagent when the reaction was carried out in this condition. In addition, twenty one intermediate compounds were also prepared. The structures of the target molecules were confirmed by IR, ¹H NMR, ¹³C NMR, MS and elemental analysis. The experiments of the biological activity for target molecules (TM-I-7a～7g) were accomplished. The experiment results of inhibiting activity against the producing of NO indicated that the compound TM-I-7g has the highest inhibition rate at the concentration of 10-4 mol/L, up to 36.78 %. The experiment results of inhibiting activity against E. Coli indicated that the compounds TM-I-7a～7g possess certain inhibiting activity against E. Coli.2. Ten divalent glycoclusters were synthesized by Ugi four-component reaction using 2, 3, 4, 6-tetra–O-acetyl-β-D-glycopyranosy amine derived from monosaccharide (glucose, galactose, mannose). Among them eight divalent glycoclusters have so far not been published. Moreover, twelve correlative intermediate compounds were also prepared. The structures of the target molecules and intermediate compounds were characterized by IR, ¹H NMR, ¹³C NMR and HRMS. The NMR spectra of representative compounds were investigated in detail by 2D NMR technique. The C, H chemical shifts of TM-III-8a, TM-III-8d, TM-IV-9a and TM-IV-9d were assigned and the coupling constant, J values, were also given out. The antitumor in vitro activities of divalent glycoclusters were determined. The results of inhibiting activities against human liver cancer cell (BEL-7402) and human lung cancer cell (A-549) showed that the target compounds possessed relatively high inhibiting activity. The TM-IV-9c has higher inhibiting activity than the other compounds at the concentration of 10-4 mol/L, up to 68.9 % and 77.2 % respectively. These results are very important for further study on the synthesis, biological activity and development of sugar drugs.