Cross Coupling Strategies towards the Synthesis of the Streptonigrin CD Moiety

Abstract

An efficient route to an appropriate model of the streptonigrin 4phenylpyridine CD moiety is reported.4-Chloro-3-nitropyridine was found to be the key precursor and its reactivity in cross coupling reactions was further investigated.We recently reported a facile route to an AB ring equivalent (1) of streptonigrin (2), a potent anticancer compound.'Our overall strategy towards the total synthesis of streptonigrin involves the use of preformed and largely prefunctionalised rings, which are linked by palladium catalysed cross coupling reactions at the points indicated in the retrosynthesis (Scheme 1).We now wish to report the synthesis of a suitably functionalised model for the CD moiety from readily available substrates via both Stille and Suzuki cross coupling methodologies.Me0 COOH H2N Me OMe 1 2 OMe Scheme 1 Starting from commercially available 3-aminopyridine and 2,3-dimethoxyphenol, the amino and hydroxy groups were converted to suitable directing metalation groups via standard m e t h o d o ~o ~y .~ Metallation