Streptomyces flocculus Streptonigrin

Methyltryptophan (92) has been shown to be a biosynthetic precursor of the antibiotic streptonigrin (93) in Streptomyces flocculus (J.K. Allen, K.D. Barrow and A.J. Jones, J.chem.Soc.Chem. Comm., 1979, 280). The antibiotic itself has been studied by other groups of chemists ( S.J. Gould and S.M. Weinreb, Fortschr.chem. Org.Naturst., 1982, 41, ofJ7). Another antibiotic, streptonlgrone (95), is metabolised hy Streptomyces sp. (A.J. Kelt, R.W. Rickards and J.-P. Wu, Antibiotics, 1985, 38, 516), but lavendamycin (94), a related alkaloid from S. lavendulae (T.W. Doyle et al.. Tetrahedron Letters, 1981, 4595), does not appear to be its natural precursor. Lavendamycin has been synthesised (A.S. Kende and F.H. Ebetino, Tetrahedron Letters, 1984, 923). 

Streptonigrin. S-Amino-6-(7-amino-5,8-dihydro-6-methoxyS,8-dioxo-2-quinolyl)-4-( 2-hydroxy-3,4-dimetk-oxyphenyl)-3-methyl-2-pyridinecarboxylic acid 5-amino-6-(7-amiito-S,8-dihydro-6-methoxy-S,8-dioxo-2-qulitolyl)-4-(2-hydroxy-3,4-dimethoxyphenyl)-3-methylptcolinic acid bruneomycin NSC 45383 Nigrin. Cj,H, 7N408 mol wt 506.46. C 59.28%, H 4.38%, N 11.06%, O 25.27%. Antitumor antibiotic produced by Streptomyces flocculus Rao,... 

Streptonigrin (7.67) is a Streptomyces flocculus metabolite. It has been shown to have its genesis in part from tryptophan (via 3-methyltryptophan) (rings C and D). A notable point is the clever use of coupling observation of this coupling in (7.67) derived... 

The antitumour agent streptonigrin (LXIX), isolated from Streptomyces flocculus, has had its structure elucidated by oxidative degradation and spectroscopic studies [304, 305]. Recently, the compound bruneomycin, obtained from Actinomyces albus var. bruneomycin, has been shown to be identical with streptonigrin [306]. Streptonigrin is a potent inhibitor of DNA synthesis [307]. The drug is highly toxic, and when administered to 10 patients... 

Streptonigrin was first isolated in 1959 in the United States from a culture of Streptomyces flocculus (/). The same compound was independently isolated in the Soviet Union a few years later from a strain of Actinomyces albus var. bruneomycini (2) and in France from S. rufochromogenes and S. echinatus (3), the antibiotic being named bruneo-mycin and rufochromomycin, respectively. The antibiotic forms dark brown crystals which are slightly soluble in water, lower alcohols, ethyl acetate or chloroform and more soluble in dioxane, pyridine, DMF or THF. Streptonigrin has UV absorption maxima in methanol at 248 nm (e 38,400) and 375—380 nm (e 17,400). It is a monobasic acid with pKa 6.2—6.4 in 1 1 dioxane water. 

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