Necatorones

The strong mutagen, called necatorin (135), was first assigned a coumaro-cinnoline structure (101), but this assignment was later revised by Steglich, who found necatorin identical with a sample of necatorone (21.2) (99, 100). 

The only natural product based on this ring system is necatorone 193. This alkaloid was isolated from a toadstool, Lactarius necator (84TL3575). This fungal metabolite showed a considerable mutagenic activity in the Ames test. A synthesis of necatorone 193 involving oxidative cyclization has been reported (Scheme 33) (85TL5975). 

Independent studies carried out by Steglich and co-workers at the same time led to the isolation of an alkaloidal pigment, necatorone (333) (Fig. 

The biogenesis of necatorone and related Lactarius alkaloids is not yet fully understood. However, in a preliminary feeding experiment, a high incorporation of tyrosine-i- C into necatorone was found when the precursor was administered to a young specimen of Lactarius necator. These... 

Fugmann, B., B. Steffan, and W. Steglich Necatorone, an Alkaloidal Pigment from the Gilled Toadstool Lactarius necator (Agaricales). Tetrahedron Letters, 25, 3575 (1984). 

Necatorone has been synthesised from 2-(3,4-dimethoxyphenyl)eth-ylamine according to the sequence of reactions shown in Scheme 83 368). The conversion of the aminophenol (526) into necatorone (524) occurs via the quinone imine intermediate which is formed by oxidative dehydrogenation of (526). The alternative mode of cyclisation involving intramolecular addition of the amino group in (526) to an incipient ortho-quinonQ does not operate the intact /7-aminophenol moiety being essential for the cyclisation to occur. 

This compound possesses the structure (525) composed of two necator-one subunits linked at the 4,4 -positions. This dark brown pigment proved extremely insoluble in organic solvents but could be characterised spectroscopically in the form of its pertrimethylsilyl derivative. Interestingly the dimer (525) has been produced in vitro by the action of horse-radish peroxidase on necatorone. 

Interest in the considerable mutagenicity of extracts of L, necator led to the isolation of necatorin , a red crystalline compound exhibiting high mutagenic activity in the Ames Salmonella assay 641,642). Necatorin , for which an alternative structure to (524) was originally proposed 642), has been shown by direct comparison to be identical with necatorone 368). 

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