Aflatoxins precursors

There are different syntheses for unsubstituted model systems of aflatoxin precursors. However, these cannot be used for total synthesis (Fig. 2.5). Compound 72 has been synthesized by Pawlowski et al. in four steps (49). Compound 73 was obtained in four steps by Snider et al. via a ketene-[2 + 2]-cycloadditicai and 2iBaeyer-Villiger oxidation (50). Mittra et al. synthesized 74 in the same way as Snider et al. (51). 

Various biosynthetic precursors of aflatoxins have been synthesized. Some of these have then been converted biosynthetically into the aflatoxins. In this section, syntheses of important aflatoxin precursors will be presented. 

O Malley GJ, Murphy Jr RA, Cava MP (1985) Aflatoxin Precursors Total Synthesis of ( )-Averufin and ( )-Nidurufin. J Org Chem 50 5533... 

Nakashima TT, Vederas JC (1982) Biosynthesis of the Aflatoxin Precursor Sterigmatocystin by Aspergillus versicolor, Spin-Echo Resolution of Isotope Shifts in C-N.M.R. Spectroscopy. J Chem Soc Chem Commun 206... 

Structurally complex fused ring flm polyketides studied in this manner include the potent carcinogen aflatoxin Bi (7/ and its precursors averufin (8) and sterigmatocystin (9) (Scheme 4). The resulting couplings were consistent with... 

The initial synthetic entry into the aflatoxin system was communicated by Buchi66,136 and reported the total synthesis of aflatoxin Bj (1). The key elements of construction for this effort were, the selective differentiation of the phloroglucinol nucleus, and the formation of the functional precursor of the ABC system in the guise of the 4-methylcoumarin (49). Upon scrutinization of this molecule, it becomes evident that all of the requisite carbon atoms (see numbers) for the constitution of the ABC ring system are indeed present, albeit not necessarily in the proper level of oxidation. This fundamental coumarin piece (49), was arrived at by the implementation of two basic strategies. 

Figure 10.2 The sterigmatocystin and aflatoxin biosynthetic pathway. The structures of the intermediates are on the left, the names of the intermediates in the middle and the A. nidulans biosynthetic genes which encode the enzymes required to convert one intermediate to the next precursor are indicated on the right. Gene names followed by a question mark i.e., stcN) indicates that the gene is predicted, not proven, to function at this particular step in the ST pathway.

MCCORMICK, S.P., BHATNAGAR, D., LEE, L.S., Averufanin is an aflatoxin Bi precursor between averantin and averufin in the biosynthetic pathway, Appl. Environ. Microbiol, 1987, 53, 14-16. 

Sterigmatocystin (ST) or dihydrosterigmatocystin (DHST) (Fig.11.1), a related dihydrofuran toxin, is the penultimate precursor of aflatoxins, and is also produced as a final biosynthetic product by a number of species such as Aspergillus versicolor and Aspergillus nidulans. Sterigmatocystin is hepatotoxic, carcinogenic, and mutagenic as well, but is less potent than aflatoxins. The common biochemical... 

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