STEPWISE APPROACH TOWARD FIRST-GENERATION NONENZYMATIC HYDROLASES

The synthesis and reactivity study of a first generation serine protea se mimic is described. Central in the design stands the possibility of stabilization of the transition state by an amino triol such as 8t. E n route to 8t, a series of amino alcohols (4-8) was obtained, the reac tivity of which was studied toward esterification by acetylimidazole ( AcIm) and by p-nitro-2,2,2-trifluoroacetanilide (PNTFA). Interesting r eactivity differences were observed between the cis-and the trans-seri es, especially between 7c and 7t (AcIm), and between 8c and 8t (PNTFA) . In both cases the results are explained by invoking extra stabilizat ion of the tetrahedral oxyanion.