Kumagai Naoya, Shibasaki Masakatsu
Laboratory of Synthetic Organic Chemistry, Institute of Microbial Chemistry (BIKAKEN), Tokyo, Japan.
J Antibiot (Tokyo). 2017 Sep 27. doi: 10.1038/ja.2017.110.
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.The Journal of Antibiotics advance online publication, 27 September 2017; doi:10.1038/ja.2017.110.
绿僵菌素是烷基柠檬酸天然产物，其特点是对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多种立体选择性全合成方法的开发。从结构上看，这些天然产物是一类杂合分子，由一条较长的烷基链和一个柠檬酸单元组成，形成了一种难以构建的不对称结构。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密集手性官能团柠檬酸单元的有效合成策略。特别强调了在高度受限的碳骨架中构建立体中心的方法。《抗生素杂志》在线优先发表，2017年9月27日；doi:10.1038/ja.2017.110 。
