Tabtoxin, synthesis

Af-Benzyloxycarbonylhydroxylamine has also been employed in the [4 + 2] cycloaddition to methyl 1,3-cyclohexadiene-l-carboxylate or -carbonitrile in a total synthesis of tabtoxin. The reaction afforded a single diastereomer 10 in good yield, and the structure was assigned by H NMR and confirmed by chemical transformations61-64. 

Baldwin and co-workers have used a nitroso Diels-Alder reaction as a key step in total synthesis of tabtoxin (17), a metabolite causing leafspot disease in tobacco.41 This group has also prepared tabtoxinine /3-lactam (18), the active principle generated by in vivo enzymatic hydrolysis of 17. 

Keywords Antibiotics Antimycins Glutarimides Tabtoxins Total synthesis... 

A variety of heterocyclic antibiotics and phy to toxins have been found to date. These compounds or their derivatives are essential for daily life as useful agrochemicals and medicines. Total and semi-synthesis of these natural products and related analogous compounds are important for the elucidation of structure-activity relationships and for further development of novel and effective agents. This chapter reviews synthetic studies of biologically active heterocycUc natural products containing nitrogen atoms in their structures, such as glutarimides, antimycins, and tabtoxins. 

For the synthesis of tabtoxin (153), the less-hindered carboxyl group of 179, derived from the amine 174, was selectively condensed with di-O-benzyl-L-threonine (180) [136] via dipivaloyl ester, and the resulting two diastere-omers were separated as benzhydryl esters 181 and 182 by recrystallization. Each diastereomer was converted to tabtoxin 153, and the diastereomer 183, which showed no biological activity on the tobacco plant. 

Scheme 17 Baldwin s synthesis of tabtoxin and ( )-tabtoxinine- 8-lactam...

Examples of synthetic studies of heterocyclic antibiotics involving nitrogen atoms in their structure (glutarimides, antimycins, and tabtoxins) have been described. Further studies including total and semi-synthesis of analogous compounds as well as natural products are essential for elucidation of the SAR studies, and for the development of novel agrochemicals and medicines. 

Nitroso-Diels-Alder cyclisations have also proved to be useful in this area and in the synthesis of non-carbohydrate natural products, e,g. tabtoxin (29). Tabtoxinine B-lactam (30) has also been prepared using this methodology with cyclisation of (31) and... 

A stereospecific synthesis of the wild-fire toxin (tabtoxin) has recently been described (2/9). 

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