Studies on New Zealand marine natural products
Degree GrantorUniversity of Canterbury
Degree NameDoctor of Philosophy
The halichondrins, isolated from the Kaikoura sponge Lissodendoryx sp., are a series of polyether macrolides displaying potent in vivo antitumour activity. As such, they represent important leads as potential anticancer drugs. This research was focused on methodology that would enhance and complement the progress of halichondrins toward clinical trials. A method was established for transforming 53-methoxyneoisohomohalichondrin B, an artefact of the methanol extraction method, to the more useful isohomohalichondrin B. A by-product of this acid treatment was identified as the C38 epimer of isohomohalichondrin B. The equilibrium character of the C38 epimerisation was studied. The production of halichondrins by aquacultured Lissodendoryx sp. has been confirmed. Haptens presenting the macrocyclic portion of the halichondrins were produced using three different linkers PMPI, PMSI and EMCR. The chemistry required to selectively oxidise the C26 methylene was established. A polymer drug conjugate incorporating a halichondrin species has been prepared. This required the modification of homohalichondrin B to form an amino halichondrin.