Synthesis of a 'propeller-like' oligoheteroaryl with alternating pyridine and oxazole motifs

Abstract

The molecular architecture of oligomeric pyridyl-oxazole compounds is key to determining their mode of interaction with G-quadruplex DNA structures, which is a family of prominent anticancer biomolecular targets. We report herein an efficient synthetic route that begins with chelidamic acid and affords, in just seven steps, an unusual 'propeller-like' pyridyl-oxazole architecture with alternating pyridine and oxazole rings, that has not been yet validated as a G-quadruplex binder. The synthesis employs Van Leusen chemistry for the construction of oxazole rings from aldehydes, and two Pd(II)/Cu(I)-mediated cross-coupling reactions involving C-H activation of oxazoles for the formation of C-C bonds between bromopyridine intermediates and oxazole fragments. This modular synthesis was designed to be amenable to the construction of analogues. © Georg Thieme Verlag Stuttgart. New York.