Total synthesis of the antitumor antibiotic streptonigrin

Abstract

Full details of the previously reported total synthesis of streptonigrin (1) are presented. The successful synthetic strategy outlined in Scheme I involves use of an imino Diels-Alder cycloaddition for construction of the pyridine C ring of 1 and a modified Friedlander synthesis for annulation of the AB quinoline quinone ring system.

Alkaloids

“…Streptonigrin was produced by Streptomyces flocculus, and its structure was determined as 381 [353]. Total synthesis of streptonigrin was reported by Weinreb and Kende [354]. The structure of meloscine (382), characterized by a unique framework, was confirmed by X-ray analysis [355].…”

The Series “Progress in the Chemistry of Organic Natural Products”: 75 Years of Service in the Development of Natural Product Chemistry

“…Steven J. Gould was then a professor at Oregon State University, Corvallis. In 1981, his co-author Steven M. Weinreb (*1941) succeeded in performing the total synthesis of streptonigrin ( 213 ), a compound showing pronounced anticancer activity. Weinreb became known for the Weinreb ketone synthesis, which enables mono-addition of an organometallic reagent to an amide.…”

A facile one-pot synthesis of 2-(2-pyridyl)quinolines via Povarov reaction

“…Their original formulation was confirmed by X-ray crystallography 3 . In addition to its unique heterocyclic structure, streptonigrin has also been found to be produced by microorganisms via a novel biosynthetic pathway 4 . Highly substituted and functionalized 7-aminoquinoline-5,8-dione, has been shown to possess potent cytotoxic properties, broad spectrum antitumor activity, antiviral properties in vitro and in vivo, 5 and to display potent antimicrobial properties 6 .…”