Slobodianiuk Y. Synthesis of functionalized 1,3-oxazoles with aliphatic substituents

The dissertation is devoted to the development of novel preparative approaches to functionalized 1,3-oxazoles decorated by alkyl substituents as MedChem relevant building blocks. A convenient four-step approach to the synthesis of (S)-4-alkyl-2-(pyrrolidin-2-yl)oxazoles starting from L-Boc-proline inspired by naturally occurring oxazole-containing peptidomimetics is described. A stereolibrary of conformationally restricted oxazole-containing amino acids, namely, all isomers of 5−pyrrolydinyl- and 5-piperidinyloxazole-4-carboxylic acids, were designed and synthesized. An efficient approach to the preparation of novel sp3-enriched 4,5-disubstituted oxazoles bearing a functional group at the C-4 position is developed. Unexpectedly was found that Base-promoted cyclization of N-Boc-ω-(4-(chlorome-thyl)oxazol-5-yl)alkylamines led to the corresponding “dimerization” products containing fused 10-, 12-, and 14-membered rings. An approach to synthesis of 2-, 4- and 5-bromooxazoles was developed.