| Coumarin and its derivatives were widely distributed throughout nature, and exhibited diverse bioactivities. Among their diverse bioactivities, we focused our discussion on the coumarin derivatives with anti-breast and anti-HIV activities in this dissertation. Progress on a number of important coumarin and its derivatives with significant anti-breast cancer and anti-HIV activity was reviewed. By analysis and comparison, the structure-activity relationships were studied, and a preliminary mechanism of action of a number of coumarin derivatives on breast cancer and the HIV virus was also studied. And then, synthesis of some coumarin derivatives with great potential application or in clinical studies was given as an example.Cancer and AIDS dieaseas are a major threat to the survival of mankind. In China and western countries, the number of patients with breast cancer or AIDS has a rising trend year by year. Thus there is an urgent to discover and synthesize new drugs. This paper aims to design and synthesize a non-nucleoside class of coumarin derivatives as the lead compounds with breast cancer and HIV inhibitory activity. In this respect, we developed a simple and efficient synthetic route to synthesize iodine-contained hydroxyl coumarin and pyran-type coumarin compounds via a total five-step reaction, such as diazotization reaction, demethylation reaction and SSA-catalyzed Pechmann reaction, from simple starting materials 3, 5-dimethoxyaniline. With the hydroxycoumarin and pyrancoumarin substrate in hand, we successfully introduced the benzothiophene, thianthrene, amide acid and sulfonamide moieties into the hydroxycoumarin and pyrancoumarin skeleton with high yields by using an optimized Suzuki coupling reaction. To further explore the impact of different substrates on breast cancer activity, coumestrol derivative (a coumarin analog) 15 containing a sulfonamide moiety is total synthesized. The structure of newly synthesized compound was confirmed by IR, NMR, HR-MS etc methods. Furthermore, the signal crystal of compound 3a, 4b, 18n was obtained as representative to futher confirm its structure.The anti-breast cancer activity of all newly synthetic coumarin derivatives 3a-c, 4a-c, 5a-d, 6a-h, 14, 15 and 18a-n on MCF-7, MDA-MB-231 cell line were evaluated by MTT assay. The results showed that these target moleculars exhibited a moderate to significant inhibitory activity on MCF-7, MDA-MB-231 cell line (such as compound 15 the IC50 were 2.0μM and 5.9μM respectively). The structure-activity relationship studies have shown that the introduction of benzothiophene, thianthrene, amide acid and sulfonamide pharmacophore into the hydroxycoumarin or pyrancoumarin skeleton were very effective to enhance the anticancer activity, while different coumarin substrate also greatly affected the activities (such as coumestrol derivative 15, the IC50 were 2.0μM and 14.2μM respectively). Moreover, the HIV inhibitory activity of compound 3a-c, 4a-c, 5a-d, 6a-h was also evaluated. The results showed that these compounds exhibited moderate inhibitory activity against HIV-RT. Furthermore, we found that compound 5a, 5b exhibited significant inhibitory activity against both breast cancer cells and HIV-RT.In this paper, the possibilities of synthesis coumarin 19 containing a chiral entecavir moiety were explored. In the course of experiments we found that iodine contained pyrancoumarin in boronic esterification was too active to self-polymerization. Meanwhile, the iodine-contained entecavir moiety was susceptible toβ-elimination. Based on these experiment results, a reasonable synthetic route for synthesis of such an interesting compound 19 was proposed, and mybe saved as a reference for the following researcher.
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