Synthesis Of Coumarin Phosphonylated Derivatives And Their Non-covalent Complexes With BSA

In order to find high bioavailability, low toxic, fewer side-effect target moleculers, the structural modification of lead compounds, from some natural active ingredients, is an important way to develop pro-drugs in recent years. Natural coumarins and their derivatives which are widely distributed in the plant kingdom have many physiological activities, such as anti-cancer, anti-HIV, antibacterial, anti-inflammation, anti-coagulant, et.al. To obtain high efficiency, low toxicity of new lead compounds, the structures of modifications of some natural products have become an important research field to obatain lower toxic compounds with high bioactivities.The structural modifications of coumarin were fully investigated in this thesis. Mustard and piperazidine were introduced into 4-hydroxycoumarin and 7-hydroxycoumarin for improving their biological activity and bioavailability. Then, the interaction of coumarin derivatives with bovine serum albumin was studied using fluorescence spectroscopy. The relating works included:1.7-hydroxylcoumarin was nitrified in methanol using concentrated nitric acid, and the precipitate was purified by recrystallisation from methanol,6-nitro-7-hydroxycoumarin was obtained based on the analysis of 2D NMR and X-ray crystal date, not 8-nitro-7-hydroxycoumarin reported by the reference. Through Atherton-Todd reaction and by adding addional small amount of potash, a series of novel 6-nitrocoumarin-7-dialkyl phosphates were synthesized. The structures of synthesized coumpounds were elucidated by IR, ESI-MS, NMR and X-ray crystal. The 1H and 13C NMR chemical shifts of one of title compounds was assigaed by 2D NMR techniques, including DEPT, H-H COSY, HSQC and HMBC. The nitration of 7-hydroxycoumarin was developed an optimized method.2. A series of chlormethine phosphorochloridate piperazidine derivatives and phenoxy phosphorochloridate piperazidine derivates were coupled with 4-hydroxy coumarin, ten novel coupounds were obtained. Their structures were elucidated by IR, ESI-MS, NMR. Electrospray ionization mass spectral fragmentation pathways of these compounds were investigated by multistage mass spectrometry.3. The interaction of chlromethine para toluene 4-coumarin phosphamide or 6-nitrocoumarin-7-diisopropyl phosphates with bovine serum albumin was studied using fluorescene spectroscopy. The result showed that small molecules are able to make flurescent of proteins quench, and the quenching process is static quenching.