Canterbury Daniel P, Scott Kristen E N, Kubo Ozora, Jansen Rolf, Cleveland John L, Micalizio Glenn C
Department of Chemistry, The Scripps Research Institute, Jupiter, FL 33458.
Department of Cancer Biology, The Scripps Research Institute, Jupiter, FL 33458.
ACS Med Chem Lett. 2013 Dec 12;4(12):1244-1248. doi: 10.1021/ml400377p.
A synthesis of C11-desmethoxy soraphen A is described that proceeds in just 14 steps from readily available starting materials. This natural product analog was identified as a target of interest in a program aimed at identifying novel natural product-inspired inhibitors of acetyl-CoA carboxylase (ACC) as potential anticancer therapeutics. While describing the most efficient synthesis of a soraphen A analog (total syntheses of the natural product have been reported that proceed in 25 to ≥40 linear steps), we also present data supporting the conclusion that C11-heteroatom functionality is a beneficial but unnecessary structural characteristic of soraphen A analogs for inhibiting ACC.
本文描述了一种C11-去甲氧基索拉非尼A的合成方法，该方法从容易获得的起始原料开始，仅需14步即可完成。这种天然产物类似物是一个旨在鉴定新型天然产物激发的乙酰辅酶A羧化酶（ACC）抑制剂作为潜在抗癌治疗药物的项目中的目标研究对象。在描述索拉非尼A类似物的最有效合成方法时（已有报道称天然产物的全合成需要25至≥40个线性步骤），我们还提供了数据支持以下结论：C11-杂原子官能团是索拉非尼A类似物抑制ACC的有益但非必要的结构特征。
