Total synthesis of 19,20-epoxydocosapentaenoic acid-ethanolamide (19,20-EDP-EA) and strategies towards the total synthesis of malabaricane triterpenoids

Yi, Bowie Zubaoyi

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https://hdl.handle.net/2142/106493 Copy

Description

Title

Total synthesis of 19,20-epoxydocosapentaenoic acid-ethanolamide (19,20-EDP-EA) and strategies towards the total synthesis of malabaricane triterpenoids

Author(s)

Yi, Bowie Zubaoyi

Issue Date

2019-12-09

Director of Research (if dissertation) or Advisor (if thesis)

Sarlah, David

Department of Study

Chemistry

Discipline

Chemistry

Degree Granting Institution

University of Illinois at Urbana-Champaign

Degree Name

M.S.

Degree Level

Thesis

Keyword(s)

• fatty acid
• total synthesis

Abstract

It is well-known that a diet rich in omega-3 fatty acids, such as docosahexaenoic acid (DHA), promotes a wide range of beneficial health effects. Two of DHA’s metabolites, epoxydocosapentaenoic acid-ethanolamide (EDP-EA) and epoxydocosapentaenoic acid (EDP), have been shown to be anti-inflammatory, anti-hyperalgesic, anti-arrhythmic, anti-angiogenic and anti-cancer. Here we describe the first total synthesis of 19,20-EDP-EA that is enabled by propargylic coupling reactions and completed in 9 steps. The method has allowed us to provide abundant materials for derivatizations of the natural product, which is something that is of interest to our collaborator, the Das group at UIUC. Malabaricane triterpenoids belong to a class of molecules defined by a 6-6-5 tricyclic carbon backbone with a trans-anti-trans ring fusion. Although they have demonstrated only limited biological activities and efficient synthetic methods already exist for the construction of their core structure, the Sarlah lab became interested in developing a total synthesis for natural products of its class after an opportunity presented itself during an investigation into a synthetic route towards the isomalabaricanes. Here we describe our attempts at synthesizing the malabaricane core first from an isomalabaricane intermediate via a divergent strategy and later through a more general approach featuring a one-step construction of tricycle from epoxyhomofarnesyl nitrile. Specifically, we were able to confirm our hypothesis that the chirality transfer feature of the Au(I)-catalyzed Rautenstrauch rearrangement as utilized in the syntheses of isomalabaricanes rhabdastrellic acid A and stelletin E was also dependable for the synthesis of the malabaricane core. On the other hand, we managed to synthesize a late-stage intermediate bearing malabaricane core that could be readily converted to a precursor for cross-coupling with isomalabaricane side chains, through which we could potentially generate the hybrids between the two families of natural products and use them to shed light on the origins of the different biological activities observed.

Graduation Semester

2019-12

Type of Resource

text

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http://hdl.handle.net/2142/106493

Copyright and License Information

Copyright 2019 Bowie Yi

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