Concise Approach to the Carbocyclic Core of the Naturally Occurring Sphingomyelinase Inhibitor Scyphostatin

A flexible strategy toward the carbocyclic core of the naturally occurring sphingomyelinase inhibitor scyphostatin, from the readily available Diels–Alder adducts of cyclopentadiene and 2-allyl-p-benzoquinone, has been devised. This approach leverages the stereochemical predisposition of the norbornyl-fused scaffolds to generate the desired stereochemical pattern and leads to a concise synthesis of the epoxycyclohexenoid core of scyphostatin with a manipulable allyl side arm.

研究人员开发了一种灵活的合成策略，用于构建天然存在的鞘磷脂酶抑制剂柱孢菌素（scyphostatin）的碳环核心，该策略以易得的环戊二烯（cyclopentadiene）与2-烯丙基对苯醌（2-allyl-p-benzoquinone）的狄尔斯-阿尔德（Diels–Alder）加合物为起始原料。该策略利用降冰片烷稠合骨架的立体化学倾向性，生成目标立体化学构型，并实现了带有可修饰烯丙基侧臂的柱孢菌素环氧环己烯类核心的简洁合成。