Tryptanthrin

Reaction of P4S10 in hot pyridine produces a crystalline solid which can be collected and used for thionations in other solvents such as acetonitrile and sulfolane. The biologically active natural products tryptanthrine, rutaecarpine, 7,8-dehydrorutaecarpine, and some related compounds have now been converted to thionated versions simply by heating the molecules with this thionating reagent in sulfolane (typically at 135 °C for 20 min) followed by a workup in water. No chromatography was necessary.

Alkyl, aryl, heteroaryl and acyl radicals have been cyclised onto the 2-position of 3H-quinazolin-4-one. The side chains containing the radical precursors were attached to the nitrogen atom in the 3-position. The cyclisations take place by aromatic homolytic substitution hence retain the aromaticity of the 3H-quinazolin-4-one ring. The highest yields were obtained using hexamethylditin to facilitate cyclisation rather than reduction without cyclisation. The alkaloids deoxyvasicinone , mackinazolinone , tryptanthrin , luotonin A and rutaecarpine were synthesised by radical cyclisation onto 3H-quinazolin-4-one.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and related environmental pollutants exert most of their adverse effects via the aryl hydrocarbon or dioxin receptor (AhR). While most potent agonists of the AhR are of synthetic origin, an increasing number of natural compounds is now recognized as receptor agonists. Our findings demonstrate that some tryptanthrin derivatives biosynthesized in incubations of Candida lipolytica with tryptophan and anthranilic acid or its derivatives activate the AhR measured as induction of cytochrome P4501A1 mRNA and protein in rat hepatocytes in primary culture. The specificity of the inducing effect of tryptanthrins was demonstrated in gel retardation experiments in Hepa-1 mouse hepatoma cells using an oliogonucleotide comprising the sequence of the dioxin-responsive element. Furthermore, unidentified AhR agonists were formed in incubations of rat feces with a minimal medium supplemented with tryptophan. It is suggested that the receptor may be part of a defense system protecting higher organisms from secondary tryptophan-derived metabolites formed by the microflora of the host or its environment.