Synthesis Of Territrem B D\E Cycle Analogs, Synthesis Of Ubiquinone-10

Alzheimer's disease (AD) is one of the most common diseases occurred in aged people around the world. The mail clinical symptom is progressive cognitive decline and mental deterioration. According to the cholinergic deficiency hypothesis of AD, one of therapeutic methods is the employment of acetylcholinesterase (AChE) inhibitors which act through inhibiting the hydrolysis of acetylcholine. Territrem B shows potent inhibitory activity against AChE with IC50 value of 7.8 nmol·L^-1 which was first isolated from the culture broth of Aspergillus terreus by Chinese scientists in 1979. Its hypotoxicity and high selectivity against AChE make become the ideal leading compound in developing new AChE inhibitors.Up to now, extensive structure-activity relationship (SAR) investigations of Territrem B have not been researched. In order to do extensive research in the pharmacophores and the structure-activity relationship of territrem B, and find new AchE inhibitors with better activity, we have done the following work: Firstly, simplification on the A/B ring system as ta electron-poor enone, then keep A/B ring system without any change. Accordingly, two types of parent compounds 2.8 and 2.9 were designed and synthesized. Then AChE inhibitory activities of the target moleculars were evaluated and primary SAR were analysed. Secondly, according to pharmacological data and literatures, compounds 2.10,2.11 and 2.12 were synthesised on the basis of compound 2.08.As the only Coenzyme Q-like substances in our bodies, Coenzyme Q10 are widespread in many of subcellular, such as mitochondria, serosa, microsomes and lysosomes and Golgi apparatus, and also have many functions in the life course of cells. As an important biochemical drug, CoQ10 has a biological activity such as an electron in mitochondsia, clinical effect in human congestive heart failure, and implications in essntial hypertension, host defense, and prevention of cardiotoxicity of adriamycin.The application of CoQ10 is vast, but the source from the animals and plants is limited. Anew approach to CoQ10 in a more easy,efficient route,excellent E- andγ- selectivities and high yield was reported with the start material solanesol...