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

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.

Name thesis:degree_name

M.S.

Level thesis:degree_level

Thesis

Discipline thesis:degree_discipline

Chemistry

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2020

Author dc:creator

• Yi, Bowie Zubaoyi

Contributors dc:contributor

• Sarlah, David

• fatty acid
• total synthesis

Statement dc:rights

• Copyright 2019 Bowie Yi

Language dc:language

en

Handle dc:identifier

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

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/106493