The Studies On Synthesis And Application Of Bisbenzylisoquinoline Compounds

Tetrandrine and demethyl-tetrandrine, which belong to bisbenzylisoquinolines,are the main biologically active constituents isolated from the dry roots of StephaniaTetrandra S. Moore. In recent reports, tetrandrine and demethyl-tetrandrine haveexhibited broad pharmacological activities including anti-cancer effect, anti-silicosiseffect, anti-hypertensive effect, anti-inflammatory feature, free radical scavengingeffect and antibacterial action. As lead compounds, tetrandrine anddemethyl-tetrandrine are through structure modification, aiming at obtaining moreactive bisbenzylisoquinoline derivatives.In this paper,18tetrandrine and demethyl-tetrandrine derivatives weresuccessfully synthesized via modifying the structure of tetrandrine (TET) anddemethyl-tetrandrine (d-TET). The bisbenzylisoquinoline betaines (BIB) were firstsynthesized including bisbenzylisoquinoline acetic betaine (BIAB),bisbenzylisoquinoline propionic betaine (BIPB), bisbenzylisoquinoline butyric betaine(BIBB). Their structures were characterized by1H-NMR,13C-NMR, IR and HR-MSspectroscopies. All of these compounds have not been reported so far. Additionally,the antioxidant activities of part of the compounds were tested by means of improvedpyrogallol autoxidation method. Meanwhile, the free radical scavenging abilities werecalculated. Vitamin C was used as a reference material. The surface tension of part ofthe compounds were measured by the wilhelmy plate method. This thesis consists offive parts. The main content of the thesis is as follows:1. The recent research progress of tetrandrine and demethyl-tetrandrinederivatives, including chemical synthesis and their applications in the fields ofpharmacological activities, was briefly reviewed.2. TET as the starting material reacted with ethyl bromoacetate and two doublequaternary ammonium salts of TET were synthesized. Their structures were characterized by1H-NMR,13C-NMR, IR and HR-MS spectroscopies. The antioxidantactivities of TET and the two derivatives were determined by means of improvedpyrogallol autoxidation method. The free radical scavenging abilities were calculated. The surface tension of N, N’-TET acetic betaine was measured by the wilhelmy platemethod.3. TET, in moderate conditions, respectively reacted with methyl2-bromopropionate, ethyl2-bromopropionate, propyl2-bromopropionate, isopropyl2-bromopropionate, n-butyl2-bromopropionate. Then esters were hydrolyzed to gainN’-TET propionic betaine. Six derivatives of TET were gained, and their structureswere characterized by1H-NMR,13C-NMR, IR and HR-MS spectroscopies. Theantioxidant activities of part of the derivatives were determined by means of improvedpyrogallol autoxidation method. The free radical scavenging abilities were calculated. The surface tension of N’-TET propionic betaine was measured by the wilhelmy platemethod.4. TET, in moderate conditions, respectively reacted with methyl2-bromobutyrate, ethyl2-bromobutyrate, propyl2-bromobutyrate, isopropyl2-bromobutyrate, n-butyl2-bromobutyrate. Then esters were hydrolyzed to gainN’-TET butyric betaine. Six derivatives of TET were gained, and their structures werecharacterized by1H-NMR,13C-NMR, IR and HR-MS spectroscopies. The antioxidantactivities of part of the derivatives were determined by means of improved pyrogallolautoxidation method. The free radical scavenging abilities were calculated. Thesurface tension of N’-TET butyric betaine was measured by the wilhelmy platemethod.5. d-TET as the starting material reacted with benzyl chloride. Three derivativesof d-TET were synthesized. They were benzyl-d-TET, bisbenzyl-d-TET,tribenzyl-d-TET. The structure of bisbenzyl-d-TET was characterized by1H-NMR,13C-NMR, IR and HR-MS spectroscopies. d-TET as the starting material reacted withethyl bromoacetate. Under strict control of reaction conditions, the reaction is highlyselective by using phase transfer catalysts.7-O-ethyl acetate-d-TET was obtained withthe structure characterized by1H-NMR, IR and HR-MS spectroscopies. 6. Conclude the thesis.