Scalable Synthesis of (-)-Thapsigargin.
Scalable Synthesis of (-)-Thapsigargin.
复制标题
（ - ） - thapsigargin的可扩展合成。
DOI：
10.1021/acscentsci.6b00313
复制
发表时间：
2017-01-25
影响因子：
18.2
通讯作者：
Baran PS
中科院分区：
文献类型：
--
作者：
Chu H;Smith JM;Felding J;Baran PS
报道了高氧合倍半萜类化合物毒胡萝卜素（1）和去甲三叶草素（2）的全合成。这些有前途的生物活性天然产物的类似物的获得仅限于繁琐的分离和半合成努力。优雅的先前的全合成证明了在36-42步过程中创建这些实体的可行性。目前报道的路线通过利用两相萜烯合成逻辑以可扩展和更简洁的方式进行。这项工作的突出特点包括应用经典的photosantonin重排和精确编排安装的多重氧化目前的愈创木骨骼。大自然制造萜烯的大胆策略，类似于圣诞树的装饰，激发了我们对毒胡萝卜素和nortrilobaline的简洁实验室路线，并可用于获得这些医学相关分子的独特类似物。
Total syntheses of the complex, highly oxygenated sesquiterpenes thapsigargin (1) and nortrilobolide (2) are presented. Access to analogues of these promising bioactive natural products has been limited to tedious isolation and semisynthetic efforts. Elegant prior total syntheses demonstrated the feasibility of creating these entitites in 36–42 step processes. The currently reported route proceeds in a scalable and more concise fashion by utilizing two-phase terpene synthesis logic. Salient features of the work include application of the classic photosantonin rearrangement and precisely choreographed installation of the multiple oxygenations present on the guaianolide skeleton. Nature’s bold strategy to make terpenes, akin to the decoration of a Christmas tree, inspires our concise laboratory route to thapsigargin and nortrilobolide and can be used to access unique analogues of these medicinally relevant molecules.