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

1. Seven novel 1-aryl aminoacetyl-4-arylacetyl thiosemicarbazides (TM-I-5a~5g) were synthesized by the techniques of ultrasonic irradiation and phase transfer catalysis while ten important intermediate compounds were also prepared. The structures of the target molecula were characterized by IR, 1H NMR, 13C NMR, 2D NMR and elemental analysis. The NMR spectra of representative target compound TM-I-5c were studied in detail. The C, H chemical shifts of the compound were assigned and the coupling constant, J values, were also given out. The three downfield proton and carbon signals in the 1H NMR and 13C NMR spectra for target compounds have been assigned for the first time. The synthetic method of target compounds has the advantages of simple operation, mild conditions and good yields. The intermediate compounds acyl isosulfocyanates, which do not need to be separated, may react directly with arylamines, the target compounds were obtained by the reaction of nucleophilic addition.2. A facile one-pot synthesis of 2, 5-disubstituted-1, 3, 4-thiadiazoles was achieved by ultrasonic irradiation and phase transfer catalysis for the first time and seven novel 2, 5-disubstituted-1, 3, 4-thiadiazoles (TM-II-5a~5g) were synthesized. This method has the advantages of mild conditions, short time, good yields, convenient, economical and environment friendly. In addition, six intermediate compounds were also prepared. The structures of the target molecula were confirmed by IR, 1H NMR, 13C NMR, 2D NOESY, MS and elemental analysis. The experiments of the biological activity for target molecula were accomplished. The experiment results of inhibiting activity against COX-2 indicated that the compound TM-II-5f had the highest inhibition rate, up to 95.59%, and yet the compound TM-II-5g exhibits weakly inhibiting activity. The target compounds didn't possess anticonvulasional activity. 3. Twelve divalent glycoclusters were synthesized by Ugi four-component reaction using carboxymethyl 2, 3, 4, 6-tetra–O- acetyl-α-D-glycol-pyranoside derived from monosaccharide (mannose, galactose, glucose). Among of them ten divalent glycoclusters have so far not been published. Moreover, nine correlative intermediate compounds were also prepared. The structures of the target molecula and intermediate compounds were characterized by IR, 1H NMR, 13C NMR and MS. The NMR spectra of representative compounds were investigated in detail by 2D NMR technique. The C, H chemical shifts of TM-III-5b and TM-IV-6b were assigned and the coupling constant, J values, were also given out. The antitumor in vitro and inhibiting Cdc25A activity of divalent glycoclusters were determined. The results showed that most of the target compounds possessed relatively high inhibiting activity against human liver cancer cell (BEL-7402). The TM-IV-6d have higher inhibiting activity than the other compounds at the concentration of 10-4 mol/L, up to 63.4%. The divalent glycoclusters (TM-IV-6a~6f) possessed inhibiting activity against Cdc25A and the TM-IV-6f had the highest inhibition rate, up to 45.83%. However, the peracetylated divalent glycoclusters (TM-III-5a~5f) didn't possess inhibiting activity. These results are very important for further study on the synthesis, biological activity and development of sugar drugs.