Synthesis And Biological Evaluation Of Tetrahydroisoquinoline And Indolinone Alkaloid Derivatives

Tetrahydroisoquinoline and indolinone alkaloids have been shown to have diverse biological activities. The aims of this thesis were to study the synthesis and biological activities of tetrahydroisoquinoline and indolinone alkaloids derivatives.The contents of the first part are the synthesis and antitumor evaluation of noscapine and its derivatives.2-Hydroxy-3-methoxybenzaldehyde as the starting material, the key intermediate-isoquinolinium iodide was prepared successfully via an eight-step route with overall yields 27%. Then a-noscapine was obtained by zinc-promoted reductive coupling reaction of isoquinolinium iodide and 3-bromo-6,7-dimethoxyphthalide. The total yield of noscapine is 6.6%.During our studies,57 target compounds including 48 novel compounds were synthesized in this part. The structures of all new compounds were unambiguously confirmed by spectroscopic methods. All of target compounds synthesized were tested in the MCF-7 and HL-60 cancer strain model in vitro. Seventeen compounds exhibited better inhibitory activities than noscapine on HL-60 tumor line. Then we examined the target compounds by tubulin binding assay. Moreover, the representative compounds were selected to evaluate their inhibitory ability on tubulin polymerization.The contents of the second part are the synthesis and biological activities study of indolinone derivatives. According to the literatures and our previous works, compounds containing the fragments of indolin-2-one and furan had shown good inhibitory activity against protein tyrosine phosphatase 1B (PTP1B) in a low micromolar range. We selected them as lead compounds to design a series of 3-furfurlidenemethylindolin-2-ones,.N-(5-formyl-2-furyl)indolin-2,3-diones, diindolin-2-ones and diindolin-2-one imines. These compounds were synthesized with the key Sandmeyer isatin reaction and Knoevenagel reaction.During our studies,69 target compounds, including 67 novel compounds were synthesized in this part. The structures of all new compounds were unambiguously confirmed by spectroscopic methods. All of target compounds synthesized were tested for their inhibitory activities by the method of pNPP. Twenty-three compounds showed good activities in the PTP1B assay, with IC50 values less than 10μM. These compounds could be studied more as antidiabetes and antiobesity lead compound. Additionally, some compounds were selected to assay their potential application in agriculture at the same time. Two compounds showed excellent inhibitory activities against Myzus persicae in vivo screening, which could be a basis of further research. Furthermore, these compounds were tested in tumor inhibition bioassay.