An Expedient Synthesis of the Antimitotic Natural Products Sarcodictyin and Eleutherobin, and Carbohydrate Analogues.

The eleutherobins and sarcodictyins are diterpenoids that belong to an elite family of microtubule-stabilizing natural products that includes the frontline cancer therapy Taxol. To date, members of this family of natural products have been overlooked as clinical candidates in large part, owing to a lack of material available from natural sources (rare marine invertebrates) or through chemical synthesis. Here, we report a concise synthesis of several members of the eleutherobin and sarcodictyin natural products using an approach that parallels Nature's strategy, with the assembly of a eunicellin intermediate followed by regio- and diastereoselective oxidations. Additionally, we report a collection of eleutherobin carbohydrate analogues that shed light on the relationship between carbohydrate structure and anticancer activity. These efforts should support and inspire the discovery of next-generation microtubule-stabilizing drugs.