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人体总胆固醇的大部分来自于体内合成,而血清低密度脂蛋白(LDL)的升高是动脉硬化和冠心病的主要危险因素。这两个发现导致人们极力寻找胆固醇生物合成的抑制剂。这种抑制剂的最合适的靶的是3-羟基-3-甲基戊二酰辅酶A(HMG-CoA)还原酶,即胆固醇生物合成的限速酶。已开发的对此还原酶具有竞争性抑制作用的二个化合物compactin和mevinolin,为治疗原发性高脂血症提供了一个新途径。eptastatin是compactin经微生物羟基化而得的HMG-CoA还原酶抑制剂,目前正在进行广泛的临床研究中。合成compactin的3β位经冬令毛霉
Much of human total cholesterol comes from in vivo synthesis, whereas elevated serum low-density lipoprotein (LDL) is a major risk factor for atherosclerosis and coronary heart disease. Both of these findings led people to look for inhibitors of cholesterol biosynthesis. The most suitable target for this inhibitor is 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, the rate-limiting enzyme for cholesterol biosynthesis. Two compounds, compactin and mevinolin, which have been developed to competitively inhibit this reductase, provide a new approach for the treatment of primary hyperlipidemia. eptastatin is a compactin microbial HMG-CoA reductase inhibitor that is hydroxylated and is currently under extensive clinical study. The 3β position for the synthesis of compactin was confirmed by Mucor