Obiettivo
Research objectives and content
The Spongistatins are a new class of naturally occurring marine metabolites (isolated from the marine sponges Spongia sp. and Spirastella sp. in the early 1970s), the structures of which have been recently disclosed. This new family of macrocyclic lactone polyethers has attracted immediate considerable attention, due to their potent antitumor activity against highly chemoresistant tumor types, such as human melanoma, lung, colon and brain cancers.
The low availability of the molecules from the natural sponges is a serious obstacle for biological screening. Therefore, a total synthesis of Spongistatin 1, the most potent molecule of the family has been planned with efforts from two chemical laboratories. The spiroketals, caractheristic units present in Spongistatin 1, will be sinthesized by the methodology develop by the group of Prof. Steven V. Ley, already successfully applied to the construction of several other natural products.
The incorporation of a degree of flexibility into the synthesis will permit the preparation of structurally related analogues, which will help in the understanding of the structure/ activity relationship of Spongistatins and their antimitotic properties.
Training content (objective, benefit and expected impact)
I consider that the University of Cambridge it is now one of the most important European research centers in Organic Chemistry. During my training stay there, under the supervision of Prof. Steven V. Ley, I expect to improve my knowledge and experience in Synthetic Organic Chemistry. At the moment I have carried out research directed to methodologic aspects and would gain very much by working on a total synthesis project. Links with industry / industrial relevance (22)
The understanding of the structure/ activity relationship of Spongistatins and their antimitotic properties are of great relevance for medicine and the pharmaceutical industry.
Campo scientifico
Argomento(i)
Invito a presentare proposte
Data not availableMeccanismo di finanziamento
RGI - Research grants (individual fellowships)Coordinatore
CB2 1EW Cambridge
Regno Unito