Efficient Access to the Functionalized Bicyclic Pharmacophore of Spirolide C by Using a Selective Diels–Alder Reaction

Abstract

AbstractA functionalized bicyclic lactam that was used as a key intermediate in an efficient synthesis of the pharmacophore of potent marine toxin spirolide C was synthesized by using a highly selective Diels–Alder reaction. To improve the reactivity of this transformation without loss of selectivity, substrates that contained a silyl ether or silatrane moiety were elaborately designed and converted into the spirobicyclic core structure with stereochemical control over the two asymmetric centers at the C7 and C29 positions. Moreover, a further C−C bond formation by using a Hiyama cross‐coupling reaction of the vinyl silatrane derivative facilitated versatile modification at the C5 position with an aryl or alkenyl substituent.