The Study On The Synthesis Of Coumarin Analogues Anti-HIV DCK

Since first reported in 1981,the acquired immune deficiency syndrome(AIDS),has become a major worldwide pandemic,which results in life-threatening opportunistic infections and malignancies.In the last decades,it has attracted great attentions of medicine-researchers to search for plant-derived anti-HIV compounds.And in recent years, DCK,synthesized from umbelliferone,showed a remarkable therapeutic value of anti-HIV and higher selectivity than anti-HIV medicine AZT(azidothymidine).Meanwhile,it owns (?)he values of high bioactivity,low vice effects and uneasily produced medicinal resistence. Now,in China,AIDS has taken a trend of rapid spread,but as to the research of its (?)herapeutic medicine,it was still in the starting-stage.There is seldom report about DCK.It is thus necessary to undertake a deep research on the synthesis of DCK,and to seek a better synthetic method.In this dissertation,first of all,a new synthetic method of the preparation of expensive and large amount used 3-Chloro3-methyl -1-butyne was performed.In this method,we used 2-methyl-3-butyne-2-ol to react with thionyl chloride in the presence of pyridine,and find the by-products were greatly reduced.Then the synthesis and separation of 7-(2-methyl -3 -butyn-2-oxyl)-Coumarin were studied.7-(2-methyl-3-butyn-2 -oxyl)-Coumarin was synthesized by the method of Iodine catalyzed reaction and Mitsunobu etherification. Microwave-synthesis was also introduced in the Iodine catalyzed reaction,and we checked the factors such as Microwave Power,Irradiation time that affect the reaction,obtained the better condition.By our experiments,we can conclude that MW-synthesis can not only greatly reduce the reaction time,but also reduce the consume of the expensive material 3-Chloro3-methyl -1-butyne compared with traditional conditions,it's a better way to synthesize the 7-(2-methyl-3-butyn-2-oxyl) Coumarin.Then,we synthesized seselin by the two different methods of cyclization from 7-(2-methyl-3-butyn-2-oxyl) Coumarin.In this experiment,we made a comparison of the advantage and shortcoming of the reaction under MW conditions with those under traditional conditions.Afterwards,we performed a catalytic asymmetric dihydroxylation for the manufacture of(+)-cis-Khellactone,seselin as material,K₂OsO₂(OH)₄ and K₃Fe(CN)₆ as oxidant,(DHQ)₂-PYR as asymmetric induction ligand.We optimized the process.At last,we got the target compound DCK by the reaction of(+) -cis-Khellactone with camphanic acid chloride. In this dissertation,all possible reaction mechanisms were discussed. In this dissertation,all main products were identified by IR,¹HNMR,¹³CNMR.