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.

The aldol condensation of acetone with acetophenone

“…This was, in part, background information for ongoing studies of elimination reactions catalyzed by steroidal imidazoles (2,3). In the course of this investigation we became aware that there was a concurrent condensation in the opposite sense, with acetone, acting as carbon nucleophile, attacking acetophenone.…”

“…Table S1 . 3 The final proportions of these three species are independent of the starting conditions. A striking feature of the kinetics was that when reaction started with the E-enone, the concentration of the Z-enone fust rose and then fell.…”

Palladium-catalyzed diaminocarbonylation: synthesis of androstene dimers containing 3,3′- or 17,17′-dicarboxamide spacers

“…As for the main goal of our present efforts in the application of homogeneous catalytic reaction of importance for synthesis, it has to be added that in general, dimeric steroids constitute a class of compounds with pharmaceutical importance [17][18][19][20][21][22][23][24], with micellular detergent activity [25], may act as ligands for proteins [26][27][28], and some of them show liquid-crystal behavior [29] and play a key role in the rate enhancement from hydrophobic binding [30].…”

Synthesis of steroidal dimers: Selective amine catalysed steroidal dimerization

“…10,11 Most of the steroidal dimmers are also well-known for their pharmacological activity. [12][13][14][15][16][17] It might be expected that polymers of steroidal ketones (or ketone derivatives) would readily be formed in reaction media of amine catalysed dimerization. 18 Here we are presenting new dimeric steroids namely cholest-5-en-3-spiro-[6 α,5 -oxa]-5 α-cholest-3 -one (2), cholest-5- * For correspondence en-7-spiro-[4 α,5 -oxa]-5 α-cholest-7 -one (4a) and 3β-substituted-cholest-5-en-7-spiro-[4 α,5 -oxa]-3 β-substituted-5 α-cholestan-7 -ones (4b, c) which were prepared from cholest-5-en-3-one (1), cholest-5-en-7-one (3a) and 3β-substituted-cholest-5-en-7-ones (3b, c), respectively by amine catalysed dimerization 18 using DMAP and xylene.…”