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Total Syntheses of the C19 Diterpenoid Alkaloids (–)-Liljestrandisine and (–)-Liljestrandinine


Wong, Alice Rose (2019) Total Syntheses of the C19 Diterpenoid Alkaloids (–)-Liljestrandisine and (–)-Liljestrandinine. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/0KR7-PP68.


A unified synthetic strategy to access diterpenoid alkaloid natural products is presented. The highly bridged hexacyclic natural products are characterized as having a hydrindane bridged piperidyl motif that is common to the C19 aconitine type diterpenoid alkaloids and the C20 napelline and denudatine type diterpenoid alkaloids. A unified strategy to the C19 and C20 diterpenoid alkaloids is developed. An asymmetric synthesis of an epoxy-hydrindane fragment enables the development of the key unified strategy, involving a 1,2-addition followed by a semipinacol rearrangement in a key fragment coupling process. The fragment coupling is demonstrated generally with a variety of substrates, including an aromatic substrate that is advanced to a key bicyclo[2.2.1]heptane intermediate towards the C20 diterpenoid alkaloids.

The developed 1,2-addition/semipinacol-rearrangement strategy is ultimately leveraged in the total synthesis of two different C19 aconitine type diterpenoid alkaloids. An asymmetric synthesis of a bridged bicyclo[3.2.1]octane fragment is presented. The bridged bicyclo[3.2.1]octane fragment is advanced through the developed 1,2-addition/semipinacol rearrangement fragment coupling strategy affording a key tetracyclic intermediate. This work ultimately culminates in the total syntheses of two natural products (–)-liljestrandisine and (–)-liljestrandinine. Key steps for the completion of the total syntheses include advancement of the key tetracyclic intermediate from the fragment coupling through a series of C–N and C–C bond forming reactions, including an intramolecular aziridination reaction and a radical cyclization.

Item Type:Thesis (Dissertation (Ph.D.))
Subject Keywords:Total Synthesis, Diterpenoid Alkaloids, Alkaloids, Synthetic Strategy, Aconitine, Denudatine, Liljestrandisine, Liljestrandinine, Talatisamine
Degree Grantor:California Institute of Technology
Division:Chemistry and Chemical Engineering
Major Option:Chemistry
Thesis Availability:Public (worldwide access)
Research Advisor(s):
  • Reisman, Sarah E.
Thesis Committee:
  • Stoltz, Brian M. (chair)
  • Fu, Gregory C.
  • Robb, Maxwell J.
  • Reisman, Sarah E.
Defense Date:3 June 2019
Funding AgencyGrant Number
National Science Foundation Graduate Research FellowshipUNSPECIFIED
Amgen Graduate FellowshipUNSPECIFIED
Record Number:CaltechTHESIS:06082019-154532666
Persistent URL:
Default Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:11728
Deposited By: Alice Wong
Deposited On:10 Jun 2019 23:12
Last Modified:21 Jun 2021 23:23

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