| Cholesteryl ester transfer protein (CETP) is a plasma glycol-protein, which is made of 476 amino-acid residues and plays a critical role in both cholesteryl esters and triglycerides transfer among lipoproteins. Inhibition against CETP would be expected to raise high density lipoprotein cholesterol levels and then reducing blood lipids to resist atherosclerosis. Thus CETP has becomed a potential target for treatment of coronary heart disease.Penicillide was isolated from the mycelia extracts of a fungus in 1974. Recently, its derivatives were found to inhibit the activity of CETP. However, the modification on the penicillide was depended on its own structure. In order to discover new CETP inhibitors based on the structure of Penicillide, we must build the parent core in a proper way and construct the chiral secondary alcohol, which is an important pharmacophore, through asymmetric reaction. In this thesis, we mainly completed the following work:1. Fragment A was synthesized with 2,3-dihydroxybenzaldehyde as material and Fragment B was synthesized with 5-amino-2-methylphenol as material. 2. Coupling products were synthesized through Ullmann coupling reaction based on the exploration of copper catalyst conditions.3. A "convergence-style " method was established to synthesize parent core ring and the construction work of Penicillide molecule skeleton was completed.4. A new method was established to construct stereochemistry of Penicillide derivatives based on the CBS asymmetric reduction and the ee value could be up to 86%.5. A route was established to synthesize Penicillide and its analogues, the synthesis work of the eight target molecule was completed and preliminary evaluation of their activities was also carried out.In this thesis, the total 71 compounds were synthesized, and among them 8 compouds were targets and 56 compounds were not reported before. All of these structures were confirmed by NMR and MS.
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