Evolution of a Unified Strategy for Complex Sesterterpenoids: Progress toward Astellatol and the Total Synthesis of (-)-Nitidasin

Daniel T. Hog, Florian M.E. Huber, Gonzalo Jiménez-Osés, Peter Mayer, Kendall N. Houk, Dirk Trauner

Research output: Contribution to journalArticle

Abstract

Astellatol and nitidasin belong to a subset of sesterterpenoids that share a sterically encumbered trans-hydrindane motif with an isopropyl substituent. In addition, these natural products feature intriguing polycyclic ring systems, posing significant challenges for chemical synthesis. Herein, the evolution of our stereoselective strategy for isopropyl trans-hydrindane sesterterpenoids is detailed. These endeavors included the synthesis of several building blocks, enabling studies toward all molecules of this terpenoid subclass, and of advanced intermediates of our initial route toward a biomimetic synthesis of astellatol. These findings provided the basis for a second-generation and a third-generation approach toward astellatol that eventually culminated in the enantioselective total synthesis of (-)-nitidasin. In particular, a series of substrate-controlled transformations to install the ten stereogenic centers of the target molecule was orchestrated and the carbocyclic backbone was forged in a convergent fashion. Furthermore, the progress toward the synthesis of astellatol is disclosed and insights into some observed yet unexpected diastereoselectivities by detailed quantum-mechanical calculations are provided. Two and a half molecules: Astellatol and nitidasin are polycyclic sesterterpenoids, posing considerable challenges for synthetic chemists. In this full account, the evolution of a synthetic strategy for these and structurally related natural products is given (see scheme). The presented work includes efforts toward a biomimetic synthesis of astellatol, a successful route for the first total synthesis of (-)-nitidasin, and quantum-mechanical investigations into unexpected diastereosectivities.

Original languageEnglish (US)
Pages (from-to)13646-13665
Number of pages20
JournalChemistry - A European Journal
Volume21
Issue number39
DOIs
StatePublished - Sep 1 2015

Keywords

  • computational chemistry
  • natural products
  • stereoselective synthesis
  • terpenoids
  • total synthesis

ASJC Scopus subject areas

  • Catalysis
  • Organic Chemistry

Fingerprint Dive into the research topics of 'Evolution of a Unified Strategy for Complex Sesterterpenoids: Progress toward Astellatol and the Total Synthesis of (-)-Nitidasin'. Together they form a unique fingerprint.

  • Cite this