Stuart Cameron

The Bohlmann–Rahtz route to functionalised pyridine scaffolds and their use in library synthesis

The Bohlmann-Rahtz reaction has been used to prepare 2,3,6-trisubstituted pyridines suitable for use in library synthesis. The synthesis of piperidine substituted nicotinic acid derivative 9 has been optimised and carried out on a large scale to give ca. 500 g of scaffold which was used in the generation of the pyridine library 11.

Partial syntheses of the trichothecene mycotoxins, calonectrin and deoxynivalenol

Abstract The partial syntheses of two trichothecenes, calonectrin ( 1 ) and deoxynivalenol ( 2 ), from a readily available derivative of the trichothecene, anguidine, are described. The methodology used should be applicable to the provision of other less abundant trichothecenes.

Chemical deoxygenation of the trichothecenes, diacetoxyscirpenol and deoxynivalenol

Based on a model study using the bicyclic epoxides (9) and (10), an efficient one-step procedure for the selective removal of the 12,13-epoxide ring of the trichothecene toxins has been devised.

Trichothecene mycotoxin interconversions: partial syntheses of calonectrin and deoxynivalenol, and of a trichothecene epi-epoxide, 3α,4β,15-triacetoxy-12, 13-epi-epoxytrichothec-9-ene

The partial syntheses of two trichothecenes, calonectrin (1)(4β,15-diacetoxy-12, 13-epoxytrichothec-9-ene) and deoxynivalenol (2)(3α,7α,15-trihydroxy-12, 13-epoxytrichothec-9-ene), from a readily available trichothecene, anguidine (3)(4β,15-diacetoxy-3α-hydroxy-12, 13-epoxytrichothec-9-ene) are described. In addition, and in order to provide further insight into the mode of action of the trichothecene mycotoxins, 3α,4β,15-triacetoxy-12, 13-epi-epoxytrichothec-9-ene (31), of the first semisynthetic trichothecene epi-epoxides, has been prepared and its X-ray crystal structure determined. In significant contrast to its natural isomer (10), epi-epoxide (31) proved to be biologically inactive.

Synthesis and biological evaluation of a trichothecene epi-epoxide, 3α,4β,15-triacetoxy-12,13-epi-epoxytrichothec-9-ene

In order to provide additional insight into the mode of action of the trichothecene mycotoxins, one of the first semi-synthetic trichothecene epi-epoxides (8) has been prepared; in dramatic contrast to its natural isomer (9), this compound proved to be devoid of significant biological activity.

Chemical deoxygenation of the trichothecenes diacetoxyscirpenol and deoxynivalenol

Based on a model study using the bicyclo[3.2.1]octane epoxy acetates (14) and (15), an efficient one-step procedure for the selective removal of the 12,13-epoxide ring of the trichothecene mycotoxins diacetoxyscirpenol (1; R = H) and deoxynivalenol (2; R = H) has been devised. The key to success proved to be use of the lower-valent tungsten deoxygenation system of Sharpless et al.