Synthesis of viridiofungins and zaragozic acids, cholesterol synthesis inhibitors

由于其有效的角鲨烯合酶抑制活性，绿霉素和萨拉戈卡酸作为开发有效的降胆固醇药物的主要化合物引起了广泛的关注。本研究的目的是发展这类化合物的有效合成方法。（真菌，丝孢菌纲）与绿霉素B和C一起。这些绿霉素具有独特的结构，由具有C-16长链的共同柠檬酸部分和芳族氨基酸残基如酪氨酸、苯丙氨酸和色氨酸组成。然而，这些化合物的绝对结构未被确定。在本研究中，我们首次合成了viridiofungin A三甲基酯，确定了其绝对构型为3S，4S，2'S。对于萨拉戈萨酸，我们设想了一种新的策略，这种策略依赖于二烯基甲醇的前所未有的双二羟基化。我们首先研究了各种二烯基甲醇的双羟基化反应，以检查非对映选择性。结果表明，该反应具有中等至优异的非对映选择性，主要的非对映异构体具有理想的构型，可用于合成萨拉戈萨酸。目前，我们正在进行基于上述策略的萨拉戈萨酸A的合成。

Both viridiofungins and zaragogic acids have attracted much attention as leading compounds for developing an effective cholesterol lowering drug because of their potent squalene synthase inhibitory activity. In this research, we aimed to develop efficient methods for the syntheses of these families of compounds.Viridiofungin A was isolated from a strain of Trichoderma viride Pers.(Fungi, Hyphomycetes) together with viridiofundin B and C.These viridiofungins have unique structures consisting of a common citric acid moiety having C-16 long chain and an aromatic amino acid residue such as tyrosine, phenylalanine, and tryptophane. However, the absolute structures of these compounds were not determined. In this research, we achieved the first synthesis of viridiofungin A trimethyl ester which allowed us to determine its absolute configuration to be 3S, 4S, 2'S.For zaragozic acids, we envisaged a new strategy which relies on unprecedented double dihydroxylation of dialkenylcarbinols. We first examined double hydroxylation of various dialkenylcarbinols to check the diastereoselectivity. As a result, we found that this reaction took place with moderate to excellent diastereoselectivity and the major diastereoisomer possessed desirable configuration for the synthesis of zaragozic acids. Now we are carrying out the synthesis of zaragozic acid A based on the above-mentioned strategy.