The development of a versatile solid phase synthesis of bicyclic polyaza heterocycles including pteridines, purines, and deazapurines is described. The strategy comprises the linking of a pre-formed pyrimidine through a thioether at the 2 or 4 position to a polystyrene resin, the cyclisation of the second ring, and the direct or oxidative cleavage of the product from the resin by nucleophilic substitution. This provides not only for substituent variation in the second ring, but also for variation at the site of cleavage. Limitations in the scope of the methodology are set by the intrinsic reactivity of pyrimidinyl 2- or 4-thioethers which, whilst undergoing ready nitration at C5, are surprisingly difficult to alkylate and acylate.
- solid phase synthesis
- heterocyclic compounds
- bicyclic polyaza heterocycles
- polystyrene resin
- nucleophilic substitution
- intrinsic reactivity
Gibson, C. L., La Rosa, S., & Suckling, C. J. (2003). A prototype solid phase synthesis of pteridines and related heterocyclic compounds. Organic and Biomolecular Chemistry, 1(11), 1909-1918. https://doi.org/10.1039/b300798g