Streptonigrinic acid

The H-NMR spectrum of the tetramethyl ester (4b) formed from streptonigrinic acid showed the presence of a primary amino group (2H, 7.84 5, exchangeable with D2O) and treatment of (4b) with nitric acid gave the desaminotetraacid (5) after ester hydrolysis. Thermal decarboxylation of (5) over soda lime produced 5-methyl-2,2 -bipyridyl (6) identical with an authentic sample. 

Miscellaneous Reactions. Some hydantoin derivatives can serve as precursors of carbonium—immonium electrophiles (57). 5-Alkoxyhydantoins are useful precursors of dienophiles (17), which undergo Diels-Alder cycloadditions under thermal conditions or in the presence of acid catalysis (58). The pyridine ring of Streptonigrine has been constmcted on the basis of this reaction (59). 

Some unusual syntheses of substituted 2,2 -bipyridines deserve mention. Tetracyclone (tetraphenylcyclopentadienone) on heating with picolinonitrile at 215°C affords 3,4,5,6-tetraphenyl-2,2 -bipyridine, whereas 5-methyl-2,2 -bipyridine and some polysubstituted 2,2 -bipyridines are obtained by the oxidative degradation of the antibiotic streptonigrin. 5-Aldehydo-6-amino-2,2 -bipyridines are obtained by acid hydrolysis of pyrido[2,3-[Pg.311]

Streptonigrin.—Details of a study of the biosynthesis of streptonigrin (139) that had earlier been published in preliminary form (cf. Vol. 9, p. 24 Vol. 10, p. 23) are now available in full papers.51 52 In essence, the new results are that labelled anthranilic acid was not incorporated into streptonigrin (139),51 that l-rather than D-tryptophan was a precursor, and that label from C-7a in tryptophan (94) appeared, it was deduced, at C-8 in (139).52 The exclusive labelling of C-8 by tryptophan indicates that rings A and B do not derive from this amino-acid. These rings do not derive from phenylalanine and tyrosine, and negative results have been obtained with shikimic acid due, at the least, to poor cellular uptake.51... 

Within the total synthesis of the antitumor antibiotics streptonigrin and lavendamycin, steiically hindered polyfunctional pyridinecarboxylic acids (87-89) have been conveniently converted to their corresponding amines by treatment with DPPA-triethylamine in refluxing benzene for 1-2S h, followed by a brief reflux after addition of water. 

Rec-lac test recA lacZ DNA-damaging agents (radiation or chemical), 4NQO, MMC, MNNG, nalidixic acid, DMS, El202, formaldehyde, UV radiation, tert-butyl hydroperoxide, cumene hydroperoxide, and streptonigrin E. coli 47... 

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,... 

In 1982, Doyle et al. reported isolation of an antibiotic, structurally related to streptonigrin (207), called lavendamycin (121) (57), the structure elucidation of which had been disclosed by the same group in 1981 (52). The n-butanol extract of a culture of S. lavendulae, strain C22030 isolated from a soil sample collected from Woolinton, New York, was treated with excess petroleum ether to precipitate crude lavendamycin, which was purified by silica gel column chromatography eluting with toluene-acetonitrile-trifiuoroacetic acid (40 40 20 and 50 30 20 v/v) solvent systems. 

A feature of the biosynthesis of a number of microbial metabolites is the fracture of aromatic rings in the precursor amino-acids pyrrolnitrin (see this Report, p. 23), anthramycin, tomaymycin, and streptonigrin (see this Report, p. 23). This is only observed rarely in the biosynthesis of plant bases, a notable example being the betalains, which are pigments in plants of the order Centro-spermae. ... 

C]Tryptophan [as (127)] was efficiently incorporated into streptonigrin, the location of all the activity at C-3 indicating that rings c and D, but not A and B, originate from this amino-acid" (the origin of rings a and B is not yet known). 

The structural dissection of the lavendamycin molecule 40 revealed a quinolinequinone (AB) and p-carboline (CDE) framework. Both these units are historically known and numerous methodologies for them have been formulated. It was therefore, hoped that the synthetic efforts towards 40 would not pose much difficulties. The synthetic tactics towards 40 revolve around the Bischler-Napieralski reaction between p-methyltryptophan and quinaldic acid to construct ring C, and in the process, bridging the two subunits. However, Roger s group preferred to extend the inverse electron demand Diels-Alder reaction, successfully demonstrated for streptonigrin, to the synthesis of lavendamycin. 

Another common use of carbopalladation is to effect a net annelation by side chain installation followed by cyclization. One example from the synthesis of a protected form of the 2-quinolone portion of streptonigrin 40 begins with iodide 37 (Scheme Heck reaction of this electron-rich fully substituted aryl iodide 37 with methyl acrylate provides the substimtion product 38. Extended reflux of 38 under acidic conditions promotes double deprotection, isomerization, and cyclization reaction yielding enamide 39. Another example from the synthesis of ( )-aurantioclavine 41 involves coupling of aryl bromide Standard Heck conditions provide the substitution product 43 in excellent yield at the appropriate oxidation state for cyclization to form the azepine ring en route to the natural product... 

Contents E. HASLAM The Metabolism of Gallic Acid and Hexahydroxydi-phenic Acid in Higher Plants. — D. G. ROUX and D. FERREIRA The Direct Biomimetic Synthesis, Structure and Absolute Configuration of Angular and Linear Condensed Tannins. — ST. J. GOULD and ST. M. WEINREB Streptonigrin. — D. J. ROBINS The Pyrrolizidine Alkaloids. — J. W. DALY Alkaloids of Neotropical Poison Frogs (Dendrobatidae). 

The procedure of Hauser and Eby has been used to prepare several substituted 4-phenyl-2-pyridones related to streptonigrin (XII-129). In model experiments, aroylacetonitriles and ketones in polyphosphoric acid give 4-aryl-2-pyridones (XU-130). 5,6-Dhnethyl-4-phenyl-2-pyridone (XII-130a) ves... 

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