Synthesis of Lamellarin alkaloids using a photoredox initiated cyclisation cascade

Our research group focuses on the synthesis of heterocycles, particularly using singlet oxygen and activation of enamides and allenamides. This chemistry can be used for the rapid construction of biologically active natural products, and heterocycles of pharmaceutically relevance.

More than 70 lamellarins and related pyrrole-derived alkaloids have been isolated and identified. While they posses a variety of unique structural features they also exhibit fascinating and significant biological properties. These include cytotoxicity and antitumor activity, multidrug resistance (MDR), HIV-1 integrase inhibition, antibiotic activity, cell division inhibition, immuno-modulatory activity, antioxidant activity, and feeding deterrence. Traditional syntheses of this natural product class compounds have centered on palladium coupling of pyrrole bromides with aryl boronic acids with subsequent alkylation of the pyrrole nitrogen or Diels-Alder reaction of a disubstituted alkynes with subsequent functional group manipulation.

Our approach will utilize our recently reported (Org. Lett 2018, 20, 1003) photoredox mediated addition of radicals to enamides, followed by subsequent nucleophile trapping. This project will develop an intramolecular variant of this unique process that will ultimately deliver a total synthesis of the core heterocyclic structure of the lamellarins. This project will significantly increase the synthetic efficiency compared to current strategies, as well as providing an excellent training platform to the prospective PhD candidate in our new state-of-the-art laboratories here at Loughborough.
Entry Requirements
Applicants should have, or expect to achieve, at least a 2:1 Honours degree (or equivalent) in Chemistry.