| Description |
The Movassaghi group has recently reported several total syntheses of epipolythiodiketopiperazine derivatives (ETPs), a class of natural products with potent biological activity. A crucial step in their synthesis oxidizes two to four tertiary C-H bonds to form tertiary alcohols using (bis)pyridine silver permanganate, but this essential synthetic step is not well understood and is not always successful. Because of the utility of this reaction in ETP synthesis as well as its potential to be useful in other systems, it was selected as an important reaction for study. Toward this end, a library of simple molecules with single potential sites of oxidation, hydantoins, were synthesized, and relative rate data was obtained via competitive rate experiments under the oxidation conditions. Using the rate data, a correlation was generated, comparing computed descriptors to the relative oxidation rates. The model generated for the hydantoins was able to predict whether 13 of 16 ETP precursors were able to undergo oxidation in this system, showing large energy barriers for ETP precursors which weren't oxidized and small energy barriers for those that were oxidized. Additionally, a single parameter * was identified, which also produced an accurate prediction for 13 of the 16 ETP precursors, with those undergoing oxidation below a certain threshold and those not undergoing oxidation above that threshold. In the context of the Movassaghi group's oxidation, this thesis describes a tactic by which simple molecules can be used to predict reaction outcomes in more complex systems. |
