Cascade cyclisation reactions and their application toward the synthesis of lactonamycin

• Main Author: Jones, Daniel Ross
• Other Authors: Parsons, Philip
• Published: Imperial College London 2018
• Subjects: 540
• Online Access: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.745320

The lactonamycins represent a class of natural products which possess significant biological activity with high potencies in cancer cell lines and against multi-drug resistant strains of bacterial infections. Here, a cascade cyclisation, developed in the Parsons group, has been used in the synthesis of the pentacyclic core of lactonamycin. The thermal cyclisation of an ene-diyne allows for a transition metal free synthesis of five of the six rings of lactonamycin in ten synthetic steps. Studies on the functionalisation of the pentacyclic core of lactonamycin have also been undertaken. A proposed strategy for the completion of the total synthesis has also been outlined. In addition, a novel method for the synthesis of highly substituted aromatic rings has been discovered in the Parsons group. This reaction involves the thermal opening of a furan ring which is induced by the ring closing reaction of a diyne / Diels-Alder cascade. This provides penta- and hexa-substituted aromatic rings with potential pharmaceutical applications as templates for drug design. Some palladium-mediated cascade cyclisation methodology of similar, alkenyl bromide analogues is also discussed.