Research On Synthesis Of Resveratrol Analogues And Their Biological Properties

The design and synthesis of resveratrol analogues, 3,5-Dimethoxy- benzyldiethylphosphite (1),3,4′,5-Trimethoxy-stilbene (2a),3,5-Dimethoxy-4′- nitrostilbene (2b),3,5-Dimethoxy-4′-aminostilbene(3),N,N′-di{4-(3′,5′- Dimethoxystyrene)benzene} oxamide (4) and DTPA-di(3,5- Dimethoxy-4′- aminostilbene) (6)( DTPA-2NH ) were described in this thesis.(1) was synthesized from 3,5-Dimethoxy- benzylbromine and triethylphosphite as raw material, the yield was 92.6 % under the optimal reaction condition(n(3,5-Dimethoxy-benzylbromine):n(triethyl phosphite) =1:2,at 130℃for 4.5 hours).(2a) and (2b) were synthesized by Witting-Hornor reaction. And (3) was synthesized by deoxidizing with Fe/HCl, the yield was 84.3% under the optimal reaction condition (n(2b):n(Fe)=1:4).(4) and (6) were synthesized by the incorporation of (3) into oxalyl chloride and DTPAA. The structure was confirmed by IR, MS, 1HNMR and element analysis.⁹⁹Tc^m-DTPA-2NH was prepared by DTPA-2NH reacted with Na⁹⁹Tc^mO4 in the presence of stannous chloride (SnCl2Ë™2H2O). The optimum labeling conditions were investigated: the amounts of DTPA-2NH and SnCl2Ë™2H2O were 5mg and 75μg, pH was 5.0.The labeled compound had good stability in vitro after 6 h in room temperature. The results of biodistribution in rats showed that the labeled compound was high concentration in liver and kidney and rapid clearance in lung and blood. All of the above mentioned results laid a foundation for further study on the anti-cancer medicaments and new radioactive drugs used for detection of them.Compounds 2a,2b,3,4 and 6 were tested in vitro for their anti-tumor activity on liver tumor cells HepG2 ,lung tumor cells H446 and their toxicity on normal liver cells L02.Their IC50 values were calculated by Spass software. The results showed that compounds 2a and 4 had better anti-tumor activity and lower toxicity.The hydrophobic constants of compounds 2a,2b and 3 were measured by a shake-flask method. The results showed that the sequence of their hydrophobic constants was different from their anti-tumor activity, but it was identical with their toxicity.