Recent advances in the synthetic studies of pestalotiopsin A and related caryophyllene-type sesquiterpenoids

Ken Ichi Takao, Kin Ichi Tadano

Research output: Chapter in Book/Report/Conference proceedingChapter

1 Citation (Scopus)

Abstract

A large number of caryophyllene-type sesquiterpenoids have been isolated from nature. Many of them show a wide range of biological and pharmacological activities. Recently, as highly oxygenated caryophyllene-type sesquiterpenoids, pestalotiopsin A and structurally related natural products such as pestalotiopsin B and C and taedolidol have been isolated from Pestalotiopsis sp. These natural products are characterized by their highly distorted bi- to pentacyclic structures, all including a gem-dimethylated cyclobutane ring as one constituent. Recently, the first asymmetric total synthesis of both enantiomers of pestalotiopsin A was completed by the authors and coworkers, thereby clarifying the previously unknown absolute stereochemistry of this natural product. These total syntheses were achieved by the following notable synthetic concepts: (1) chiral auxiliary-based symmetric synthesis of the functionalized cyclobutane derivatives through the Lewis acid-catalyzed [2 + 2] cycloaddition between dimethyl ketene diethyl ketal and propiolamide equipped with the Oppolzer's camphorsultam and (2) an intramolecular Nozaki-Hiyama-Kishi cross-coupling mediated by a Cr(II)/catalytic Ni(II) system for high-yielding nine-membered ring formation. In this chapter, the authors also summarize their synthetic approaches toward pestalotiopsin A and related caryophyllene-type sesquiterpenoids, reported so far by Procter and coworkers and Paquette and coworkers. The Procter group has utilized the SmI2-mediated reductive 4-exo-trig cyclization for the efficient construction of the polysubstituted cyclobutane moiety. The Paquette group has demonstrated the effectiveness of the zirconocene-mediated ring contraction strategy for access to the enantiomerically pure multiply functionalized cyclobutane moiety. The highlights of their synthetic endeavors aimed at the total synthesis of pestalotiopsin A are discussed in this chapter.

Original languageEnglish
Title of host publicationStudies in Natural Products Chemistry
PublisherElsevier B.V.
Pages161-187
Number of pages27
ISBN (Print)9780444626158
DOIs
Publication statusPublished - 2013

Publication series

NameStudies in Natural Products Chemistry
Volume39
ISSN (Print)1572-5995

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Keywords

  • Caryophyllene-type sesquiterpenoid
  • Intramolecular Nozaki-Hiyama-Kishi coupling
  • Pestalotiopsin A

ASJC Scopus subject areas

  • Drug Discovery
  • Organic Chemistry

Cite this

Takao, K. I., & Tadano, K. I. (2013). Recent advances in the synthetic studies of pestalotiopsin A and related caryophyllene-type sesquiterpenoids. In Studies in Natural Products Chemistry (pp. 161-187). (Studies in Natural Products Chemistry; Vol. 39). Elsevier B.V.. https://doi.org/10.1016/B978-0-444-62615-8.00005-9