Mevinolin, a fungal metabolite, was isolated from cultures of Aspergillus terreus. The structure and absolute configuration of mevinolini and its open acid form, mevinolinic acid, were determined by a combination of physical techniques. Mevinolin was shown to be 1,2,6,7,8,8a-hexahydro-beta, delta-dihydroxy-2,6-dimethyl-8-(2-methyl-1-oxobutoxy)-1-naphthalene-hepatanoic acid delta-lactone. Mevinolin in the hydroxy-acid form, mevinolinic acid, is a potent competitive inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase [mevalonate: NADP+ oxidoreductase (CoA-acylating), EC 1.1.1.34]; its Ki of 0.6 nM can be compared to 1.4 nM for the hydroxy acid form of the previously described related inhibitor, ML-236B (compactin, 6-demethylmevinolin). In the rat, orally administered sodium mevinolinate was an active inhibitor of cholesterol synthesis in an acute assay (50% inhibitory dose = 46 microgram/kg). Furthermore, it was shown that mevinolin was an orally active cholesterol-lowering agent in the dog. Treatment of dogs for 3 weeks with mevinolin at 8 mg/kg per day resulted in a 29.3 +/- 2.5% lowering of plasma cholesterol.

中文翻译：

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Mevinolin：羟甲基戊二酰辅酶A还原酶和胆固醇降低剂的高效竞争抑制剂。

Mevinolin是一种真菌代谢物，是从土曲霉培养物中分离出来的。mevinolini及其开放酸形式mevinolinic acid的结构和绝对构型是通过物理技术相结合确定的。Mevinolin被证明是1,2,6,7,8,8a-六氢-β，δ-二羟基-2,6-二甲基-8-（2-甲基-1-氧代丁氧基）-1-萘-庚酸三角洲-内酯。羟酸形式的羟甲基萘甲酸，羟甲基亚麻酸，是3-羟基-3-甲基戊二酰辅酶A还原酶的有效竞争性抑制剂[甲羟戊酸：NADP +氧化还原酶（CoA-酰化），EC 1.1.1.34]；对于先前描述的相关抑制剂ML-236B（compactin，6-demethylmevinolin）的羟基酸形式，其Ki值为0.6 nM可以与1.4 nM相比。在老鼠里 在急性试验中（50％抑制剂量= 46微克/ kg），口服维甲酸钠是胆固醇合成的活性抑制剂。此外，已经表明，美维诺林是狗中的口服活性降胆固醇剂。每天以8 mg / kg的甲米三环素治疗犬3周，可使血浆胆固醇降低29.3 +/- 2.5％。