Synthetic Studies of Viridiofungins, Broad-Spectrum Antifungal Agents and Serine Palmitoyl Transferase Inhibitors
Synthetic Studies of Viridiofungins, Broad-Spectrum Antifungal Agents and Serine Palmitoyl Transferase Inhibitors
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Viridiofungins、广谱抗真菌剂和丝氨酸棕榈酰转移酶抑制剂的合成研究
DOI：
10.1038/ja.2017.110
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Masakatsu Shibasaki
中科院分区：
文献类型：
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作者：
Naoya Kumagai;Masakatsu Shibasaki
Viridiofungins 是烷基柠檬酸酯天然产物，其特征在于对角鲨烯合酶和丝氨酸棕榈酰转移酶具有抑制作用。它们作为广谱抗真菌剂以及鞘脂生物合成阻断剂的活性激发了几种立体选择性全合成方法的发展。从结构上讲，这些天然产物是一个杂合分子家族，包含较长的烷基链和柠檬酸单元，呈现出难以获得的不对称结构。在此，我们总结了这类有吸引力的天然产物的合成方法，包括构建具有高极性的致密手性功能化柠檬酸单元的熟练合成策略。特别强调在高度受限的碳框架中提供立体中心的方法。
Viridiofungins are alkyl citrate natural products characterized by their inhibitory effects on squalene synthase and serine palmitoyl transferase. Their activities as broad-spectrum antifungal agents as well as blocking agents for the biosynthesis of sphingolipids have inspired the development of several approaches toward their stereoselective total synthesis. Structurally, these natural products are a family of hybrid molecules comprising a longer alkyl chain and a citric acid unit, rendering an asymmetric structure that is difficult to access. Herein, we summarize the synthetic approaches to this attractive class of natural products, including proficient synthetic strategies for constructing the densely and chirally functionalized citric acid unit with high polarity. Particular emphasis is placed on methods for furnishing stereogenic centers in the highly constrained carbon framework.