Plet, J.R.H.; (2008) Studies towards the synthesis of tagetitoxin. Doctoral thesis , University of London.

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Abstract

Tagetitoxin is a phytotoxin which was first isolated in 1981 from a strain of Pseudomonas syringae pv. tagetis. It is viewed as a challenging synthetic target for a variety of reasons:;- The molecule shows a unique biological activity as a specific inhibitor of RNA polymerase HI. It has found some use within the biological community in the study of transcription.;- Its structure is assigned upon spectroscopic and chemical analysis of biological extracts, and has some ambiguities.;- Its probable structure contains a unique bicyclic ring system which has never been synthesised before.;- The natural product itself has never been synthesised.;In this thesis, we report an efficient, high-yielding and short synthetic route to the core structure of tagetitoxin from simple carbohydrate starting materials. The initial research focused on the ring expansion of a bicyclic 1,3-oxathiolane to the corresponding 1,4-oxathiane using metallocarbene chemistry via Stevens rearrangement. This reaction proved not to be feasible on the studied precursors possible reasons for this failure are discussed herein. The second route investigated involved the intramolecular cyclisation of a thiol onto an electron-deficient ketone. Initial studies on unfunctionalised substrates proved unsuccessful, however, the use of a carbohydrate as starting material was more efficient and the core structure of tagetitoxin was synthesised from D-glucose in 32% yield over 15 steps. Studies towards a more complex substrate were carried out and key intermediates were successfully synthesised. Future plans towards the total synthesis of tagetitoxin are laid out based on the findings of this thesis.

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