Use this URL to cite or link to this record in EThOS:
Title: Studies towards the synthesis of tagetitoxin
Author: Gama, Yannick
ISNI:       0000 0004 7654 045X
Awarding Body: University of East Anglia
Current Institution: University of East Anglia
Date of Award: 2018
Availability of Full Text:
Access from EThOS:
Access from Institution:
The natural product tagetitoxin is a phytotoxin which was first isolated from the bacterium Pseudomonas syringae pv. tagetis in 1981. Tagetitoxin is an inhibitor of chloroplast and bacteria RNAP and also selectively inhibits RNAP III in eukaryotes. Multiple biological mechanisms of inhibition and several structures have been proposed for tagetitoxin. The structural ambiguity and potential useful biological activity have driven the desire for a total synthesis of tagetitoxin's proposed structures; none of which of yet have been successful. This body of research describes the recent developments our group has contributed towards the synthesis of tagetitoxin. The main objective was to synthesize targets 323a and 323b which both contain the oxathiobicyclo[3.3.1]nonane ring system found in two of the proposed structures of tagetitoxin. Our initial strategy focused on four synthetic routes derived from diacetone mannose (DAM). In this strategy, the route nearest to obtaining the bicyclic core of 323a and 323b was the dithiane-reduction route. In this route, the target precursors 389 and 415 (and analogues) were made, but attempted thioacetate deprotection and concomitant cyclization of the thiol/thiolate onto a ketone or sulfonate ester to yield the oxathiobicyclo[3.3.1]nonane ring system led to either decomposition or complex mixtures. This failure was attributed to the presence of isopropylidene groups hampering the cyclization by imposing steric constraints on ring closure. We then conducted synthetic routes starting from D-galactose in the D-galactose and exo-glycal routes (avoiding the use of any isopropylidene groups). Failure to insert a hydroxyl-methylene group on the C-1 position by anomeric nitrile anion chemistry or ring-opening an anomeric spiro-epoxyacetal with TMSCN led us to attempt a hydroboration-oxidation on an exo-galactal derivative which was partially successful. Optimization of the hydroboration-oxidation pathway in the exo-glycal route is promising for future research.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available