Model studies toward the synthesis of the bioactive diterpenoid, harringtonolide

Abstract

In model studies towards the synthesis of harringtonolide, the construction of the tropone moiety via arene cyclopropanation was investigated. The installation of the lactone ring was accomplished by way of a Diels-Alder cycloaddition of various indenones and \u1d6fc-pyones. The incorporation of the key bridge methyl group and subsequent control of its stereochemistry is also outlined

Synthesis of novel molecular probes inspired by harringtonolide

“…Finally, while our motivation is defined by a continuing quest to identify new privileged structures and scaffolds embedded within natural products for drug discovery, 24,25 screening the cycloheptatriene probe library also has potential to provide additional insights into the already rich biological activity of harringtonolide itself. In this respect, our approach complements the ongoing efforts of others 26,27 to find accessible routes to the synthesis of 1 and closely 35 related analogues such as hainanolidol for screening and drug discovery.…”

Total Synthesis of the Diterpenoid (+)‐Harringtonolide

“…In 1998, Mander's group demonstrated a groundbreaking total synthesis of (±)‐hainanolidol, which constituted a formal synthesis of 1 . The elegant strategy featured arene cyclopropanation and a subsequent ring expansion for the construction of the tropone moiety, though the formation of the THF ring of the natural product at an early stage proved to be unfavorable –. More recently, Tang et al.…”

Synthesis of naturally occurring tropones and tropolones

“…Mander’s group also tried to improve their synthesis of hainanolidol and complete the synthesis of the related bioactive congener, harringtonolide. 161–166 However, none of these further efforts led to the completion of harringtonolide.…”