| Suksdorfin (1), isolated from the fruit of Lomatium suksdorfii, has an angular pyranocoumarin skeleton with interesting biological properties, especially its anti-HIV activity. Modification of 1 yielded DCK and 4-methyl-DCK, which demonstrated extremely potent inhibitory activity against HIV-1 replication in H9 lymphocytic cells. Even though the mechanism of action of DCK and its analogues is still unknown, current mechanistic studies indicated that they do not inhabit RT, integrase, or protease in the HIV life cycle. Therefore, DCK and its analogues might inhibit HIV-1 replication by a novel mechanism.So it is very important to discover the relationship between the structure and the activities, which can offer significant information and clue for further modification and explore the structural aspect of target bio-molecule.According to the principle of bioisomerism, we have synthesized some novel heterocycles contained N,N, N,O ., O,S and S,O by displacing the O,O in the DCK respectively. In the 1-thio-DCK and 7-thio-DCK series, the compounds with 8,8-dihydro still displayed notable activity for anti-HIV. These results promote us to synthesize the analogues of DCK with different substituents at 8-position and attempt to obtain an insight of target molecule structural aspect at this area interacted with 8-position of DCK derivatives.In this thesis we reported the synthesis of 8-hydro-DCK, 8,9-cycloalkano-DCK and 8,8-dialkyl-DCK from propagyl alcohol, cycloalkanones and alkanones respectively. Meanwhile we tried to introduce aryls and some substituents with heteroatoms, such as -OR, -SR and -NR2, into the DCK skeleton. Total of 44 unknown compounds and 12 DCK analogues have been synthesized and structures of them were identified with spectra and necessary analysis.All of the unknown compounds had been screened for inhibition of HIV-1 replication in H9 lymphocytes and their bioassay data primarily showed that the compound 8-methyl-8-ethyl-4-methyl-DCK (32a) exhibited potential activity. The bioassay data showed the 8-position of DCK is serious sensitive site to be modified and there are only a very little cavity with 1.5 X 4-6A at relative area of target bio-molecule. .In this research a number of interesting unexpected chemical behaviors of some compounds and reactions were encountered. To all of these, we have taken a careful investigation to discover their reasonable nature. They are summarized as following:a. Completed a route for synthesis a -alkynol from ketone , but it is not satisfactory for aldehyde to get the corresponding a -alkynol;b. Obtained a kind of unexpected dihalo-compounds from the halogenation of a -alkynols and confirmed their structures, which can be converted into a type of novel tetracyclic heterocycles regio-selectively;c. Discovered the substituents at propargylic site of 7-(2-propynyloxy)-4-methylcumarins have great effect on activities and products in the next ring closure reaction: the more bulk of substituents the more five-membered ring closure products to be formed;d. Discovered the reaction 4-methyl-2H-pyrano[6,5-h]2H-chromen-2-one with NBS was not occurred a radical substitution at propargylic position but an addition at 9,10-duble bond;e. Discovered the members of the D-ring in 2H-pyrano[6,5-g]cycloalkano[2,l-b] 2H-chromen-2-ones will substantively effect the speed of their Sharpless asymmetric dihydroxylation reaction and the dehydrogen will happen when the products of AD which holdsome alkyl at 9,10-double bond react with (IS)-camphanolic chloride;f. Found the a , a -dibromoalkyl t-butyl ester might be a potent acyl equivalent, according to the unexpected result in the reaction of benzyl t-butyl ester with NBS followed by 4-methyl-7-hydroxycumarin.
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