Toward “E‐Ring‐Free” Lamellarin Analogues: Synthesis and Preliminary Biological Evaluation

Abstract

AbstractSince the discovery of anticancer properties of a naturally occurring hexacyclic marine alkaloid Lamellarin D, the attempts have been made to prepare its synthetic analogues and elucidate the effects of each structural component on their activity profile. While F‐ring‐free, A‐ring‐free and B‐ring‐open lamellarins are known, E‐ring‐free analogues have never been investigated. In this work, we developed a facile and straightforward synthetic method toward E‐ring‐free lamellarin analogues based on the [3+2]‐cycloaddition. For the first time, we prepared several pentacyclic lamellarin analogues without E‐ring in their structure and assessed their cytotoxicity in a panel of cancer cell lines in comparison with several hexacyclic lamellarins. E‐ring‐free lamellarins were devoid of cytotoxicity due to their poor solubility in cellular environment.