Streptonigrin analogs

In recent years a considerable number of streptonigrin analogs have been synthesized which are primarily on variations of the 5,8-quinoline quinone structure with different substituents at C-2, C-6, and C-7... 

Several publications by Rao and coworkers (18, 65, 66) have reported syntheses of various streptonigrin analogs. A key pyridine intermediate used in this work was the system (82), lacking the streptonigrin D-ring, which was prepared via the straightforward sequence shown in Scheme 11. 

Lown, j. W., and S.-K. Sim Studies Related to Antitumor Antibiotics. Part VII. Synthesis of Streptonigrin Analogs and Their Single Strand Scission of DNA. Canad. J. Chem. 54, 2563 (1976). 

In 1986, Isshiki et al. reported on the isolation and structure elucidation of an analog of streptonigrin called demethylstreptonigrin (208), which was determined to be lO -O-demethylstreptonigrin, from a strain of S. albus, which also produces streptonigrin (83). 

In 1992, a third analog of streptonigrin, this time with no substituent at C-10, was reported by Liu et al. (84). lO -Desmethoxystreptonigrin (209 was isolated from the fermentation broth of a strain of S. albus, a solid sample collected in Yosemite National Park, California. 

In 1992, Balzarini etal. synthesized the analog of streptonigrone, strepton-igrone-2 -imine (291) (Scheme 30) 132), from streptonigrin (207). Treatment of streptonigrin with ethyl chloroformate afforded anhydride 288, reaction of which with NaNa afforded the corresponding azide 289, which was immediately used for further reactions. Decomposition of the azide in... 

Several streptonigrin quinoline-quinone analogs have also been synthesized by Rao (16) (Scheme 6) using a modified Friedlander synthesis for construction of the quinoline system. The compound prepared which structurally is most like the natural product is the pyridylquinoline-quinone (59). Chalcone (55), prepared from 3,5-dimethoxybenzaldehyde and 2-acetylpyridine, was nitrated to give (56). Reductive cyclization of (56) with sodium dithionite led to quinoline (57) which upon treatment with nitric acid/sulfuric acid yielded nitroquinone (58) in 50% yield along with 40% of a product of straightforward mononitration. Reduction of the nitro group of (58) and 0-methylation with diazomethane afforded (59). 

Rao, K. V. Streptonigrin and Related Compounds III. Synthesis and Microbiological Activity of Destrioxyphenylstreptonigrin and Analogs. J. Heterocycl. Chem. 14, 653 (1977). 

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