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.

本研究开发了一种灵活的合成策略，以易得的环戊二烯与2-烯丙基对苯醌的狄尔斯-阿尔德（Diels–Alder）加合物为起始原料，构建天然存在的鞘磷脂酶抑制剂scyphostatin的碳环核心。该策略利用降冰片烷稠合骨架的立体化学倾向性，生成目标立体构型，最终简洁合成了带有可修饰烯丙基侧臂的scyphostatin环氧环己烯类核心。