The Design And Synthesis Of Resdelasu

AIDS is an acquired immune deficiency syndrome, which is caused byretrovirus HIV. Since the first AIDS sufferer was reported in 1981, 70 millionpepole have been infected with HIV in the world, and 20 million of them died.AIDS has become a main menace to human health. Anti-HIV drugs aredivided into four groups on the basis of mechanism and they are nucleosidereverse transcriptase inhibitor (NRTIs), non-reverse transcriptase inhibitor(NNRTIs), protease inhibitors (PIs) and fusing inhibitor. On the other hand,because of the incessant variation of HIV, HIV is tolerance of widly-usedmedicines. Although effective drugs are used in treating HIV, which havedeclined dead ratio, the number of people infected with HIV is increasingsharply in recent years. It is the high time that we take effective measures toempolder new anti-HIV drugs.Generally speaking, HIV can destroy immunity system, which cause thehuman body to lose resistent ability against various pathogeny. And thenvarious infections and tumours occurred, ultimately leading to death. Theanti-HIV drugs are widely used at present, if we can empolder a new drug,which has functions of not only the antivirus activity but also improvinghuman immunity, it can provide a new idea for AIDS treatment. In this study,we aim to link a natural immunocompetent compound to an anti-HIVcompound. We expect that the new compound can enhance the ability ofanti-variability. It has not only the effect of the antivirus activity but alsoimprovement of humen immunity.According to combibation principles, we select a natural immunocompe-tent compound resveratrol (trans -3, 5,4′-trihydrolystilbene) and an anti-HIVcompound delavirdine intermediate (1-[3-[(1-methylethyl)amino]-2-pyridinyl]-4[(5-amino-1H-indol-2-yl)-carbonyl]-piperazine) were selected as lead comp-ounds. Hydroxy group of resveratrol and amid of delavirdine intermediatewere chosen as reaction sites. Different cyclic anhydrides were used as joinedmolecules. The mol ratio of delavirdine intermediate and resveratrol was 1:1.Because of the difference in hydroxy groups of resveratrol, six targetmolecules were designed. Considering the difficulty in the synthesis ofdelavirdine intermediate and the high cost of resveratrol, phenol and anilinewere chosen as modle compounds. Different cyclic anhydrides were used asjoined molecules in order to investigate the feasibility of different cyclicanhydrides serving as joined molecules.Phenol and aniline were chosen as modle compounds. Succinic anhydride,maleic anhydride and phthalic anhydride were used as joined molecules. Wesynthesize with two different routes : 1.esterification after amidation;2.amidation after esterification. The results reveal as followes : 1.Using succinicanhydride as joined molecule,the aiming structure is obtained through twodifferent routes. While using maleic anhydride and phthalic anhydride, themain products are N-phenylimides. 2.The esterification of different cyclicanhydrides with phenol catalyzed by acid and alkali is difficult to react and itbecomes easy when phenol was transformed to sodium phenoxide. 3.Amidation and esterification with DCC is characteristic of easy operationcontrol and high yield.According to the study of the model experiment, succinic anhydride wasselected as joined molecule. The mol ratio of delavirdine intermediate andresveratrol is 1:1. Two different routes were used to design and synthesize thetarget molecule : 1.esterification after amidation;2.amidation after esterifi-cation. Selecting the first letters of resveratrol, delaviradine and succinicanhydride, the new compound was named as resdelasu. The results reveal : 1.3 or 5 substitution was the main product, named as resdelasu. 2. the isomer ofresdelasu is difficult to obtain, which was seperated by repeating TLC. 3. Theroute of amidation after esterification is better than that of esterification afteramidation. The low yield of the route of esterification after amidation is due tothe new cyclic compound.The metabolizing of resdelasu in wistar rat was studied. The results showthat the chemical bond of ester ruptures in the body of the wistar rat, givingimmunocompetent resveratrol and anti-HIV compound 29.In a word, resdelasu have been successfully designed and synthesizedaccording to combibation principles. Meanwhile after comparing two routinesand studied the metabolizing of resdelasu in wistar rat, an optimized route wasobtained. It would provide a new direction on the research of new type ofanti-HIV drugs in our country.