Streptonigrin and related compounds III. Synthesis and microbiological activity of destrioxyphenylstreptonigrin and analogues

Synthesis of three tricyclic analogues of streptonigrin, based on the 2‐(2′‐pyridyl)quinoline‐5,8‐dione system and with the characteristic substitution pattern of rings A and C of streptonigrin is described. The C‐ring precursor, in the form of a substituted 2‐acetylpyridine was condensed with either 3‐hydroxy‐5‐methoxy‐2‐nitrobenzaldehyde or 3‐hydroxy‐4‐methoxy‐2‐nitrobenzaldehyde, followed by reductive cyclization and oxidation to the corresponding quinones 12 and 29 . The 7‐amino substitution was introduced in 12 via bromination and azidation. The 6‐amino substitution was introduced through direct reaction of 29 with sodium azide. Destrioxyphenylstreptonigrin 2 was twice as active and the 6‐amino‐7‐inethoxy analogue 4 was as active as streptonigrin in a microbiological assay. A 4′‐bromo analogue of 2 was 60% as active as streptonigrin.