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Applications of a Concise and General Strategy for the Syntheses of Transtaganolide and Basiliolide Natural Products


Gordon, Jonny Robert (2015) Applications of a Concise and General Strategy for the Syntheses of Transtaganolide and Basiliolide Natural Products. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/Z99021P4.


Herein are described the total syntheses of all members of the transtaganolide and basiliolide natural product family. Utilitzation of an Ireland–Claisen rearrangement/Diels–Alder cycloaddition cascade (ICR/DA) allowed for rapid assembly of the transtaganolide and basiliolide oxabicyclo[2.2.2]octane core. This methodology is general and was applicable to all members of the natural product family.

A brief introduction outlines all the synthetic progress previously disclosed by Lee, Dudley, and Johansson. This also includes the initial syntheses of transtaganolides C and D, as well as basiliolide B and epi-basiliolide B accomplished by Stoltz in 2011. Lastly, we discuss our racemic synthesis of basililide C and epi-basiliolide C, which utilized an ICR/DA cascade to constuct the oxabicyclo[2.2.2]octane core and formal [5+2] annulation to form the ketene-acetal containing 7-membered C-ring.

Next, we describe a strategy for an asymmetric ICR/DA cascade, by incorporation of a chiral silane directing group. This allowed for enantioselective construction of the C8 all-carbon quaternary center formed in the Ireland–Claisen rearrangement. Furthermore, a single hydride reduction and subsequent translactonization of a C4 methylester bearing oxabicyclo[2.2.2]octane core demonstrated a viable strategy for the desired skeletal rearrangement to obtain pentacyclic transtaganolides A and B. Application of the asymmetric strategy culminated in the total syntheses of (–)-transtaganolide A, (+)-transtaganolide B, (+)-transtaganolide C, and (–)-transtaganolide D. Comparison of the optical rotation data of the synthetically derived transtaganolides to that from the isolated counterparts has overarching biosynthetic implications which are discussed.

Lastly, improvement to the formal [5+2] annulation strategy is described. Negishi cross-coupling of methoxyethynyl zinc chloride using a palladium Xantphos catalyst is optimized for iodo-cyclohexene. Application of this technology to an iodo-pyrone geranyl ester allowed for formation and isolation of the eneyne product. Hydration of the enenye product forms natural metabolite basiliopyrone. Furthermore, the eneyne product can undergo an ICR/DA cascade and form transtaganolides C and D in a single step from an achiral monocyclic precursor.

Item Type:Thesis (Dissertation (Ph.D.))
Subject Keywords:transtaganolide, basiliolide, natural product, total synthesis, asymmetric synthesis, Ireland-Claisen/Diels-Alder Cascade
Degree Grantor:California Institute of Technology
Division:Chemistry and Chemical Engineering
Major Option:Chemistry
Thesis Availability:Public (worldwide access)
Research Advisor(s):
  • Stoltz, Brian M.
Thesis Committee:
  • Grubbs, Robert H. (chair)
  • Reisman, Sarah E.
  • Dervan, Peter B.
  • Virgil, Scott C.
  • Stoltz, Brian M.
Defense Date:10 November 2014
Record Number:CaltechTHESIS:04082015-185228801
Persistent URL:
Default Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:8817
Deposited By: Jonathan Gordon
Deposited On:16 Apr 2015 00:07
Last Modified:08 Nov 2023 00:39

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