Total Synthesis of (+)-Siladenoserinol A

Abstract

AbstractThe total synthesis of (+)-siladenoserinol A (1) was accomplished. The bicyclic acetal core, a 6,8-dioxabicyclo[3.2.1]octane skeleton, was constructed by Au(III)-catalyzed cycloisomerization of 6,7-dihydroxy-2-alkynoate. A serinol side chain was introduced by the Julia–Kocienski olefination and the other side chain was efficiently introduced by the Horner–Wadsworth–Emmons reaction with glycerophosphocholine-containing phosphonoacetate, and selective sulfamation of the serinol moiety yielded (+)-1. The synthetic (+)-1 exhibited potent inhibitory activity against p53–Hdm2 interaction comparable to that of the natural product. In contrast, the desulfamate derivative did not show the inhibitory activity. Notably, its benzoyl analog exhibited more potent activity than (+)-1.