A water soluble dimeric steroid with catalytic properties. Rate enhancements from hydrophobic binding

Abstract

Dimeric steroids can be formed by reductive amination of terephthalaldehyde with 3-amino steroids using cyanoborohydride. An amino group in the 11β-position can be blocked using a formyl group, and this can be removed by acid hydrolysis after dimerization. Trifluoroacetyl is not a suitable blocking group; although it can be removed by acid hydrolysis from monomeric steroids, it was only removed from the dimer under forcing conditions which caused degradation. The dimeric steroid is a catalyst for the hydrolysis of arylpropionate esters with good leaving groups. Acylation is markedly accelerated by hydrophobic binding of the aryl group of the substrate to the steroids. Rate enhancements, relative to imidazole, of up to 5.5 × 102 were obtained, and analysis of the data shows that the potential rate enhancement is 1.1 × 105. The magnitude of the hydrophobic binding is consistent with what was seen with earlier catalysts. Aggregation, even at very low concentrations, was a problem with anionic substrates.