Aflatoxins B

Title: Aflatoxins B
Literature References: Aflatoxins are a closely related group of secondary fungal metabolites shown to be mycotoxins. They are produced by Aspergillus flavus Link ex Fries, the causative principle of turkey "X" disease; and by Aspergillus parasiticus: Sargeant et al., Nature 192, 1096 (1961); Hesseltine et al., Proc. 1st U.S. Japan Conf. Toxic Microorganisms, Honolulu, Hawaii 1968, p 202. Aflatoxins have been reported to naturally occur in peanuts, peanut meal, cottonseed meal, corn, dried chili peppers etc. However, the growth of the mold itself does not always indicate the presence of toxin since the yield of aflatoxin depends on growth conditions such as moisture, temperature, substrates, and aeration as well as genetic requirements. These heterocycles are now characterized as aflatoxins B1, B2, G1, G2, M1 and M2 (milk toxins) and B2a, G2a: Büchi, Rae in Aflatoxin, L. Goldblatt, Ed. (Academic Press, New York, 1969) pp 55-75. Toxic material is separated chromatographically into 4 distinct compounds based on fluorescent color (blue = B, green = G with subscripts relating to relative mobility): Nesbitt et al., Nature 195, 1062 (1962); Sargeant et al., Chem. Ind. (London) 1963, 53. B1 is one of the most potent environmental mutagens and carcinogens known. B2 and G2 are the less toxic dihydro derivs of B1 and G1: Asao et al., J. Am. Chem. Soc. 85, 1706 (1963); 87, 882 (1965), and B2a and G2a are the 2-hydroxy derivs of B2 and G2: Dutton, Heathcote, Biochem. J. 101, 21P (1967); Chem. Ind. (London) 1968, 418. Isoln of B3 (parasiticol), a possible metabolite of G1, from A. flavus: J. G. Heathcote, M. F. Dutton, Tetrahedron 25, 1497 (1969). Aflatoxins R0 (aflatoxicol), P1, Q1, RB1, RB2, and D1 are also known: P. F. Schuda, Top. Curr. Chem. 91, 77-106 (1980). Total syntheses of aflatoxins B1 and G1: Buchi et al., J. Am. Chem. Soc. 88, 4534 (1966); Knight et al., Chem. Commun. 1966, 706; Büchi, Weinreb, J. Am. Chem. Soc. 93, 746 (1971). The extreme toxicity and carcinogenicity of aflatoxins may be due to their inhibition of nucleic acid synthesis by either direct interaction with enzymes involved or by a toxin-DNA template: Clifford, Rees, Nature 209, 312 (1966); Sporn et al., Science 151, 1539 (1966). See also Wogan et al., Food Cosmet. Toxicol. 12, 681 (1974). Inhibition of salt-induced conversion of B-DNA to Z-DNA by aflatoxin B1: A. Nordheim et al., Science 219, 1434 (1983). Prepn of the exo-8,9-epoxide of B1, the metabolic deriv thought to be responsible for B1's carcinogenicity: S. W. Baertschi et al., J. Am. Chem. Soc. 110, 7929 (1988). uv spectrum of B2: Hartley et al., Nature 198, 1056 (1963). Physicochemical data for B1: A. E. Pohland et al., Pure Appl. Chem. 54, 2219 (1982). Toxicity data: Carnaghan et al., ibid. 200, 1101 (1963); G. Büchi et al., Life Sci. 13, 1143 (1973). Symposium on toxicology and synthesis: J. Toxicol. Toxin Rev. 8, 1-416 (1991). Review and evaluation of studies of carcinogenic action in laboratory animals and humans: IARC Monographs 10, 51-72 (1976). Comprehensive reviews: Goldblatt, Econ. Bot. 22, 51-62 (1968); Detroy et al., "Aflatoxin and Related Compounds" in Microbial Toxins Vol. VI, A. Ciegler et al., Eds. (Academic Press, New York, 1971) pp 3-178; W. F. Busby, Jr., G. N. Wogan in ACS Monograph Series no. 182, entitled "Chemical Carcinogens," vol. 2, C. E. Searle, Ed. (American Chemical Society, Washington DC, 2nd ed., 1984) pp 945-1136. Review of chemistry and syntheses: P. F. Schuda, loc. cit.; of biosynthesis: M. W. Sinz, W. T. Shier, J. Toxicol. Toxin Rev. 10, 87-121 (1991).
Derivative Type: Aflatoxin B1
CAS Registry Number: 1162-65-8
CAS Name: (6aR-cis)-2,3,6a,9a-Tetrahydro-4-methoxycyclopenta[c]furo[3¢,2¢:4,5]furo[2,3-h][1]benzopyran-1,11-dione
Molecular Formula: C17H12O6
Molecular Weight: 312.27
Percent Composition: C 65.39%, H 3.87%, O 30.74%
Properties: Crystals, mp 268-269°. Exhibits blue fluorescence. [a]D -558° (c = 0.1 in CHCl3). [a]D -480° (c = 0.1 in DMF). uv max (ethanol): 223, 265, 362 nm (e 25600, 13400, 21800). LD50 orally in day old duckling: 18.2 mg/50 gm body wt (Carnaghan); i.p. in newborn mice: 9.50 mg/kg body wt (Büchi).
Melting point: mp 268-269°
Optical Rotation: [a]D -558° (c = 0.1 in CHCl3); [a]D -480° (c = 0.1 in DMF)
Absorption maximum: uv max (ethanol): 223, 265, 362 nm (e 25600, 13400, 21800)
Toxicity data: LD50 orally in day old duckling: 18.2 mg/50 gm body wt (Carnaghan); i.p. in newborn mice: 9.50 mg/kg body wt (Büchi)
Derivative Type: Aflatoxin B2
CAS Registry Number: 7220-81-7
CAS Name: (6aR-cis)-2,3,6a,8,9,9a-Hexahydro-4-methoxycyclopenta[c]furo[3¢,2¢:4,5]furo[2,3-h][1]benzopyran-1,11-dione
Molecular Formula: C17H14O6
Molecular Weight: 314.29
Percent Composition: C 64.97%, H 4.49%, O 30.54%
Literature References: The 8,9-dihydro deriv of aflatoxin B1.
Properties: Crystals, mp 286-289°. Exhibits blue fluorescence. [a]D -492° (c = 0.1 in CHCl3). uv max (ethanol): 265, 363 nm (e 11700, 23400). LD50 orally in day old duckling: 84.8 mg/50 gm body wt (Carnaghan).
Melting point: mp 286-289°
Optical Rotation: [a]D -492° (c = 0.1 in CHCl3)
Absorption maximum: uv max (ethanol): 265, 363 nm (e 11700, 23400)
Toxicity data: LD50 orally in day old duckling: 84.8 mg/50 gm body wt (Carnaghan)
CAUTION: The aflatoxins are listed as known human carcinogens: Report on Carcinogens, Eleventh Edition (PB2005-104914, 2004) p III-8.
Aflatoxins G Aflatoxins M Afloqualone Agaricic Acid Agmatine