Ergochrome biosynthesis

IV. Investigation of Ergochrome Biosynthesis with Labeled Precursors. 173... 

Other authors (ApSimon et al., 1965 Davis et al., 1969) considered the possibility that the ergochromes and other benzophenone derivatives could be formed by condensation of two monobenzene units, 24 and 25. Thus, in the case of ergochrome biosynthesis, the two building units would first have to condense to the anthraquinone. However, this would contradict the well-confirmed evidence that anthraquinones of this type are generated from only one polyketide chain. 

For the investigation of ergochrome biosynthesis, microorganisms were required which produce ergochromes steadily and which accept labeled precursors efficiently. Lichens as Parmelia entotheiochroa, which grow extremely... 

IV. INVESTIGATION OF ERGOCHROME BIOSYNTHESIS WITH LABELED PRECURSORS... 

C(9), and C(12), which could be determined separately with the degradation reactions mentioned above (see Fig. 4), were particularly instructive for the investigation of ergochrome biosynthesis. 

The most interesting reaction of ergochrome biosynthesis is the oxidative ring cleavage of the anthraquinone precursor. To establish whether it occurs before or after dimerization of the anthraquinone units, the incorporation of appropriately labeled benzophenone derivatives or bisanthraquinonyls might be investigated. As the labeled bisanthraquinonyls (32, 38-40) were available from the methods, mentioned before, they were used for biosynthetic experiments (Franck and Flohr, 1977). 

It is remarkable that besides the main precursor chrysophanol (75), emodin (71) and islandicin (73) are also incorporated into ergochromes. The incorporations are, respectively, 3.6 and 11.8 times less than for chrysophanol (75), but still significant. As emodin (71) and islandicin (73) arise from the same polyketide precursor (15), their incorporation represents an offshoot of ergochrome biosynthesis, the participation of which was precisely established (see Table VI). Only few comparative incorporations with differently labeled precursors have been carried out in other natural product areas. Therefore, it is still uncertain to what extent such branching of biosynthetic pathways occurs. 

After the proof that ergochrome biosynthesis occurs by oxidative ring cleavage of anthraquinones (Franck et ai, 1966, 1968, Groger et al., 1968), this previously unknown biogenetic reaction was established for further natural products, which are also secoanthraquinones (Table IX). 

Revised structures of secalonic acids A. B, C, D Hooper er at., Chem- Commun. 1971, 111 eufem, J. Chem. Soc. (C) 1971, 3580. Crystal and molecular structure of secalonic acid A C. C. Howard er al. J. Chem. Soc. Perkin Trans. I 1976, 1820. Identity of secalonic acid A with mtothein Yoshioka et al, Chem. Pharm. Bull 16, 2090 (1968). Biosynthesis of secalonic acid A I. Kurobane et al., Tetrahedron Letters 1978, 1379. Review of secalonic acids and other ergochromes Franck, Flasch in Fortschr. Chem. Org Naturst. 36, 151-206 (1973). 

Franck, B. The biosynthesis of ergochromes. In The Biosynthesis of Mycotoxins (P. S. Steyn ed.), pp. 157-191. Academic Press, New York 1980 Leistner, E. Biosynthesis of plant quinones. In The Biochemistry of Plants, Vol. 7, Secondary Plant Products (E. E. Conn, ed.), pp. 403-423. Academic Press, New York 1981 Sankawa, U. The biosynthesis of anthraquinoid mycotoxins from Penicillium islandicum Sopp and related fungi. In The Biosynthesis of Mycotoxins (P. S. Steyn, ed.),pp. 357-394. Academic Press, New York 1980... 

Franck, B. The Biosynthesis of the Ergochromes. In P. S. Steyn, The Biosynthesis of Mycotoxins. A Study in Secondary Metabolism. London-New York Academic Press. 1980. 

The benzophenone 26 was considered a key compound in the biosynthesis of the ergochromes, e.g., secalonic acid A (1). It could be transformed to secalonic acid A (1) via the dienone 27 by oxidative ring closure, stereospecific enone reduction, and oxidative dimerization. The necessary structural requirements for two oxidations proceeding by the phenol oxidation mechanism are present. 

The isotope positions in a metabolite from an incorporation experiment can be ascertained for by NMR spectroscopy and for and by chemical degradation. Both approaches were applied in the elucidation of the biosynthesis of the ergochromes. 

The results of experiment 1 (Table YIII) allow the assumption that the biosynthesis of the isolated ergochromes proceeds via the following sequence BB -> BD BC CC. This presumes, however, that the dilution of the radioactive ergochromes, formed during the feeding experiment by... 

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