Solid-phase synthesis of benzoxazoles from 3-nitrotyrosine

A method to synthesize benzoxazoles on solid phase using 3-nitrotyrosine as a scaffold has been developed. The synthesis couples N-protected 3-nitrotyrosine to polystyrene via a Wang-type linker. The polymer-supported 3-nitrotyrosine is deprotected and the resultant primary amine converted to a tertiary amine via sequential reductive alkylation using aromatic followed by unhindered aliphatic aldehydes. The phenol is acylated, and the nitro group is reduced using SnCl(2). The resulting amino ester is then dehydratively cyclized to a benzoxazole. The synthesis was developed for a large mix and split (50 x 50 x 50) combinatorial library. The single compounds presented herein represent a diverse array of the types of monomers amenable to the chemistry developed.