Large hydrophobic interactions with clearly defined geometry. A dimeric steroid with catalytic properties

Abstract

. Can. J . Chem. 60,747 (1982). The steroid dimer a,a'-bis(17~-(4'-imidazolyl)-ll-keto-5a-androstan-3~-amino)-p-xylene, 3. has been synthesized by reductive amination o f 17P-(4'-imidazolyl)-5a-androstane-3,11-dione by p-xylenediamine in the presence o f sodium cyanoborohydride, and by reductive amination o f terephthalaldehyde by 3P-amino-I7P-(4'-imidazolyl)-5a-androstan-lI-one. Introduction We have previously (1) reported studies of the imidazolyl steroid, 1, which can act as a catalyst, in aqueous solution, for active esters %a-d, and which shows a marked specificity for esters with a hydrophobic acyf group, such as 2b-d, with 2d being the best substrate found so far. Careful analysis of the kinetic behavior of these reactions showed that there was a potential rate enhancement, due to favorable hydrophobic interactions between steroid and ester, of as much as 156-fold for a phenanthrene ring interacting with the steroid, but that much of this was masked by unavoidable rate-retarding steric effects in the vicinity of the reaction center, so that only a 3.6-fold rate enhancement was observable. In related studies of enolization catalyzed by 1 (2) it was found that the same hydrophobic effect was present and the steric retardation was less, so that more of the potential effect became apparent; in fact a 118fold rate enhancement relative to imidazole was directly observable.A clear conclusion from these experiments was that in order to get a large rate enhancement for ester hydrolysis, a greater area of hydrophobic contact between substrate and catalyst was essential. A conceptually simple way to achieve such an increased area of contact would be to use dimeric

Bioorganic Chemistry

“…So far, the bis( 11 )-keto derivative has been prepared and increased catalysis by 3000-fold over that of simple imidazole has been observed (397). This way, a three-dimensional frame is built and the substrate is expected to be trapped in the "jaw" ofthe dimeric catalyst where hydrophobic binding now comes from both faces of the substrate reaction center.…”

Synthesis, Spectroscopic and Theoretical Studies of New Quasi-Podands from Bile Acid Derivatives Linked by 1,2,3-Triazole Rings

“…The potential applications of these compounds include use as delivery vehicles for biological molecules, as molecular containers as well as hydrogelators. Bile acid dimers can be used for the synthesis of macrocyclic compounds as artificial receptors [18,19,20,21,22]. Furthermore some derivatives of bile acids are very good organogelators [23,24,25].…”

Dimeric and Oligomeric Steroids

“…A dimeric steroid with catalytic properties was reported by Guthrie and co-workers (Scheme ). The steroid dimer 42 was synthesized by reductive amination of monomer 41 by sodium cyanoborohydride.…”