Using Diels–Alder reactions with anthracene and anthrone towards the synthesis of berkeleyamide A

This work details the approach to produce berkeleyamide A, a known anti-inflammatory molecule. There are three synthetic routes to make this compound, but all use a chiral pool approach and have limited ability to change the functional groups on the molecule. Therefore, it was not possible to produce similar molecules and test for anti-inflammatory capabilities at lower concentrations.
This thesis sets out to identify a more flexible method to produce berkeleyamide A, allowing the modification of functional groups of the compound and increasing the yield of the final product. By enabling the production of berkeleyamide A compounds with differing functional groups, this work opens up future research into these substituted group berkeleyamide A compounds as anti-inflammatory agents.
This work uses anthracene and anthrone as auxiliaries which are attached to maleimide upon which desymmetrisation reactions can be performed. To attach anthracene and its derivatives to maleimide a Diels-Alder reaction was used. The desymmetrisation reactions performed on maleimide included a Grignard reaction and reduction reactions.
To remove the anthracene auxiliary a retro Diels-Alder reaction would be required. The most common method to accomplish this is to use FVP but this method requires expensive specialised equipment so other methods were used. A microwave reactor was used but again, this method required high temperatures. An oxyanion-initiated retro Diels-Alder reaction was performed which required swapping the anthracene auxiliary for an anthrone auxiliary. The oxyanion retro Diels-Alder reaction was performed using potassium hydride with good yields (72-74%).
The synthesis proposed in this report makes a common intermediate with a literature synthesis to make berkeleyamide A and improves upon the yield of the literature synthesis. The reported literature yield for the common intermediate was 22% and the yield of the synthesis detailed in this report was 27%, although this was racemic.